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August 2021 Volume 15 / Number 8 Novel oral inhibitor may INSIDE IBD & INTESTINAL block intestinal damage DISORDERS Inexpensive dye in celiac disease tracks digestive transit time BY HEIDI SPLETE versity of Mainz (Germa- Eat a “blue muffin” for science. • 9 MDedge News ny) and colleagues. Celiac disease is driven

elations novel oral inhibitor in part by the enzyme R of transglutaminase transglutaminase 2, and a edia M A2 appears to block transglutaminase 2 inhibi- Microscopic colitis gluten-induced mucosal tor known as ZED1227 has liniC This cause of diarrhea is C damage in patients with been tested safely in phase often overlooked. • 11 ayo

M celiac disease at three 1 trials, they reported. These best practices advice statements were written because of different doses, based on “ZED1227 targets the FROM THE AGA increasing rates of bariatric/metabolic surgery, said Dr. Vivek Kumbhari. proof-of-concept trial data intestinal mucosa pre- JOURNALS from 132 patients. dominantly and thereby AGA Clinical Practice Update “Currently, no drug ther- mediates protection; thus, Network apy reliably prevents the it is unaffected by the meta-analysis ranks effects of dietary gluten complexity of the food ma- H. pylori regimens or has been approved by trix and is less dependent Standard triple therapy is Early complications regulators to treat celiac on the timing of ingestion in trouble. • 22 disease,” which remains of gluten-containing food,” an unmet need in these the researchers explained. LIVER DISEASE after bariatric/ patients, many of whom In a study published in Calories may struggle with symptoms the New England Jour- outweigh nutrients in metabolic surgery even when they adhere to nal of Medicine (2021 diets for fatty liver a gluten-free diet, wrote Jun 30. doi: 10.1056/ Two diets BY WILL PASS miliarity with available Detlef Schuppan, MD, of NEJMoa2032441), the face off. • 30 MDedge News Johannes Gutenberg Uni- See Celiac · page 10 approaches for managing he American Gas- postoperativeinterventions toleaks. specific troenterological According to lead au- ID of underlying link between red meat, TAssociation recently thor Vivek Kumbhari, MD, published a clinical prac- PhD, director of advanced tice update concerning endoscopy, department of CRC holds early intervention potential endoscopic evaluation and gastroenterology and hepa- management of early com- tology, Mayo Clinic, Jackson- BY WILL PASS an alkylating mutational value of large-scale molec- plications after bariatric/ ville, Fla., and colleagues, MDedge News signature, according to in- ular epidemiologic studies metabolic surgery. the update was written in vestigators. and suggests potential for The seven best practice consideration of increasing mechanistic link be- early, precision dietary in- advice statements, based rates of bariatric/metabolic Atween red meat con- colorectal mutational sig- tervention, reported lead on available evidence and surgery. sumption and colorectal natureThis ishas the been first associated time a author Carino Gurjao, MSc, expert opinion, range from “Bariatric/metabolic sur- cancer (CRC) has been with a component of diet, of the Dana-Farber Cancer a general call for high fa- See Complications · page 20 which demonstrates the See Link · page 21

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1_3_9_10_20_21_GIHEP21_08.indd 1 7/21/2021 3:23:56 PM †NEWS LETTER FROM THE EDITOR: Catching up with ourselves ugust is a month that we traditionally Finally, read about a novel oral therapy reserved for rest and recovery. But un- that may provide substantial relief for celiac Afortunately, there seems to be little of patients. This randomized trial of a transglu- either as we recover from COVID-19, deal with taminase inhibitor was published in the New the care that has been delayed, try to under- England Journal of Medicine and may provide stand issues of health inequity, and manage our hybrid reimbursement landscape. So let’s set those new hope for this difficult condition. issues aside for a bit and Top patient case get back to science. Bariatric therapy is an area in In this month’s cover which gastroenterologists should stories, we can read about play an increasingly prominent role, some astounding accom- regularly bring their questions to the AGA plishments. A fantastic in conjunction with our surgical PCommunityhysicians with (https://community.gastro.org) difficult patient scenarios study comes from Dana- and metabolic colleagues. to seek advice from colleagues about therapy Farber Cancer Institute, and disease management options, best practices, Boston, where researchers Dr. Allen and diagnoses. Here’s a preview of a recent pop- found 900 colorectal can- ular clinical discussion: cers from nurses who had participated in the My term as Editor in Chief will end with Brock Doubledee, DO, wrote the following in long-running Nurse’s Health Studies. The re- the September issue. Megan Adams, MD, JD, “Xeljanz for Crohn’s”: searchers completed a whole-exome sequence MSc, will take over and provide insights and “I have a 20-year-old female with moderate- on both normal and tumor tissue and then opinions beyond my past missives. I thank ly active Crohn’s disease who has now failed Christopher Palmer and the excellent Front- Humira, Remicade, Entyvio and Stelara. The contained in the Health Studies. With this in- line Medical Communications staff who find only option I know of for her at this time is formation,linked findings they toconnected the nutritional a tumor-associated information topics and compose articles for us. Finally, Xel janz, however her insurance will not ap- mutation to the ingestion of red meat, which the publication department at the American prove this medication given its lack of FDA may suggest a causal link for the known associ- Gastroenterological Association is unparal- approval. I would be interested to know if ation between red meat and CRC. leled, led by Erin Landis with Brook Simpson anyone has any other recommended options AGA has published a detailed clinical practice and now Jillian Schweitzer. I am fortunate to or has had success with getting insurance ap- update about endoscopic management of com- return to the AGA Governing Board as Secre- proval. If you have had success I would appre- plications after bariatric/metabolic surgery. tary/Treasurer and work with our new pres- ciate any articles or guidance you have utilized Bariatric therapy is an area in which gastroen- ident, John Inadomi, as well as Tom Serena, a to gain this approval.” terologists should play an increasingly promi- great friend and AGA CEO. See how AGA members responded and join nent role, in conjunction with our surgical and John I Allen, MD, MBA, AGAF the discussion: https://community.gastro.org/ metabolic colleagues. Editor in Chief posts/24445.

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Editor in ChiEf, Gi & hEpatoloGy nEws Gi & hEpatoloGy nEws is the official newspaper of the American frontlinE mEdiCal CommuniCations John I. Allen, MD, MBA, AGAF Gastroenterological Association (AGA) Institute and provides the gastroenterologist soCiEty partnErs with timely and relevant news and commentary about clinical developments Editor in ChiEf, thE nEw GastroEntEroloGist Executive Editor Kathy Scarbeck, MA and about the impact of health care policy. Content for Gi & hEpatoloGy nEws Vijaya L. Rao, MD Editor Christopher Palmer is developed through a partnership of the newspaper’s medical board of editors assoCiatE Editors (Editor in Chief and Associate Editors), Frontline Medical Communications Inc. Creative Director Louise A. Koenig Megan A. Adams, MD, JD, MSc Gyanprakash A. Ketwaroo, MD, MSc and the AGA Institute Staff. “News from the AGA” is provided exclusively by the Director, Production/Manufacturing Ziad Gellad, MD, MPH, AGAF Larry R. Kosinski, MD, MBA, AGAF AGA, AGA Institute, and AGA Research Foundation. All content is reviewed by the Rebecca Slebodnik Kim L. Isaacs, MD, PhD, AGAF Sonia S. Kupfer, MD medical board of editors for accuracy, timeliness, and pertinence. To add clarity and National Account Manager Joshua Norton Charles J. Kahi, MD, MS, AGAF Wajahat Mehal, MD, PhD context to important developments in the field, select content is reviewed by and 512-375-8202, [email protected] commented on by external experts selected by the board of editors. Editors EmEritus, Gi & hEpatoloGy nEws Senior Director of Classified Sales Tim LaPella, Colin W. Howden, MD, AGAF The ideas and opinions expressed in Gi & hEpatoloGy nEws do not necessarily 484-921-5001, [email protected] Charles J. Lightdale, MD, AGAF reflect those of the AGA Institute or the Publisher. The AGA Institute and Frontline Medical Communications Inc. will not assume responsibility for damages, loss, Advertising Offices 7 Century Drive, Suite 302, Editor EmEritus, thE nEw GastroEntEroloGist or claims of any kind arising from or related to the information contained in Parsippany, NJ 07054-4609, 973-206-3434 Bryson Katona, MD, PhD this publication, including any claims related to the products, drugs, or services Editorial Offices 2275 Research Blvd, Suite 400, aGa institutE staff mentioned herein. Advertisements do not constitute endorsement of products on Rockville, MD 20850, 973-206-3434 Managing Editor, GI & HepatoloGy News, Jillian L. Schweitzer the part of the AGA Institute or Frontline Medical Communications Inc. Managing Editor, tHe New GastroeNteroloGIst, Ryan A. Farrell POSTMASTER Send changes of address (with old mailing label) to GI & Senior Publications Manager, Brook A. Simpson Hepatology News, Subscription Service, 10255 W Higgins Road, Suite 280, FRONTLINE Director of Publications Lindsey M. Brounstein Rosemont, IL 60018-9914. MEDICAL COMMUNICATIONS Vice President of Publications Erin C. Landis RECIPIENT To change your address, contact Subscription Services at 1-800-430- Corporate 5450. For paid subscriptions, single issue purchases, and missing issue claims, call VP, Sales Mike Guire ffiCErs of thE nstitutE o aGa i Customer Service at 1-833-836-2705 or e-mail [email protected] VP, Member Marketing & Digital Production Amy Pfeiffer President M. John M. Inadomi, MD, AGAF The AGA Institute headquarters is located at 4930 Del Ray Avenue, Bethesda, MD President, Custom Solutions JoAnn Wahl President-Elect John M. Carethers, MD, AGAF 20814, [email protected]. Circulation Director Jared Sonners Vice President Barbara Jung, MD, AGAF Director, Custom Programs Patrick Finnegan Secretary/Treasurer John I. Allen, MD, MBA, AGAF Gi & hEpatoloGy nEws (ISSN 1934-3450) is published monthly for $230.00 per year Vice President, Proprietary Conferences, MedscapeLive ©2021 by the AGA Institute. All rights reserved. No part of this publication may be reproduced or transmitted by Frontline Medical Communications Inc., 7 Century Drive, Suite 302, Parsippany, NJ in any form or by any means, electronic or mechanical, including photocopy, recording, or any information David J. Small, MBA storage and retrieval system, without permission in writing from the publisher. 07054-4609. Phone 973-206-3434

2 August 2021 / GI & Hepatology News

02_GIHEP21_08.indd 2 7/21/2021 5:19:00 PM †IBD & INTESTINAL DISORDERS Can laparoscopic lavage beat resection for acute perforated diverticulitis?

BY HEIDI SPLETE an average of 5 years’ follow-up. support laparoscopic lavage as MDedge News Secondary outcomes included stoma Quality of Life scores. an option for perforated purulent prevalence, diverticulitis recurrence, questionnaire or Cleveland Global diverticulitis, but shared decision- evere complications at 5 and secondary sigmoid resection. Balance secondary making will be essential for better years were no different for Severe complications were sim- pros and cons optimal patient management, the Spatients with perforated pu- ilar for the lavage and resection Laparoscopic lavage is not common researchers concluded. rulent diverticulitis who underwent groups (36% and 35%, respective- practice today in the United States, laparoscopic peritoneal lavage or ly), as were the overall mortality the researchers noted. In clinical Similar outcomes, but colon resection, according to data rates (32% and 25%, respectively). practice guidelines issued in 2020, unanswered questions from 199 individuals treated at 21 the American Society of Colon and Even though the primary outcome hospitals in Norway and Sweden. Rectal Surgeons strongly recom- of disease-related morbidity was But it may yet prove appropriate in “Laparoscopic lavage is faster mend colectomy over laparoscopic similar for both groups, “the is- the right patient. and cost-effective but leads to lavage for the treatment of left-sid- sue still remains regarding when Acute perforated diverticulitis ed colonic diverticulitis (Dis Colon and how, if ever, this therapeutic with peritonitis remains a challeng- a higher reoperation rate and Rectum. 2020 Jun;63[6]:728-47). approach should be considered ing complication with high morbid- recurrence rate, often requiring However, the European Society of for purulent peritonitis,” Kellie ity and mortality among patients Coloproctology’s guidelines state E. Cunningham, MD, and Brian S. with diverticular disease, and bow- secondary sigmoid resection.” that laparoscopic lavage is feasi- Zuckerbraun, MD, both of the Uni- el resection remains the standard ble for patients with peritonitis at versity of Pittsburgh, wrote in an of treatment, Najia Azhar, MD, of Hinchey stage III (Colorectal Dis. accompanying editorial (JAMA Surg. Skåne University Hospital, Malmö, The prevalence of stoma was sig- 2020 Jul. doi: 10.1111/codi.15140). 2021;156[2]:128). Sweden, and colleagues wrote. Although laparoscopic lavage has Short-term data suggest that compared with the resection group were limited primarily by the exclu- the obvious advantages of avoiding laparoscopic lavage with drainage (8%nificantly vs. 33%, lower P = in .002). the lavage However, group, sionThe of findings 50% of ofeligible the current patients study be- a laparotomy and stoma, previous and antibiotics might be a viable secondary operations (including cause of challenges associated with studies have shown a higher rate alternative, but long-term data are reversal of stoma) were similar conducting randomized trials in of early reoperations and recurrent lacking, they said. between the lavage and resection emergency settings, the researchers diverticulitis, despite lower stoma In the Scandinavian Diverticulitis groups, performed in 26 lavage noted. However, the number of ex- (SCANDIV) trial, published in JAMA patients (36%) versus 24 resection cluded patients and their baseline they said. In addition, “patients who Surgery (2021;156[2]:121-7), re- patients (35%). characteristics after exclusion were areprevalence immunosuppressed and equal mortality or would rates, be searchers randomized 101 patients Diverticulitis recurrence was very similar in the two groups, and expected to have a higher mortality to laparoscopic peritoneal lavage the study represents the largest and 98 to colon resection. With 3 lavage, compared with the resection randomized trial to date to exam- source control should likely not be groupsignificantly (21% vs.more 4%, common P = .004), in the ine long-term outcomes in patients offeredrate with this failure therapy.” to achieve definitive analysis included 73 patients who researchers noted. with perforated diverticulitis. A “philosophical” argument could underwentpatients lost laparoscopic to follow-up, lavage the final and In the laparoscopic lavage group, “Laparoscopic lavage is faster and be made in favor of laparoscopic la- 69 who underwent resection. The 30% (n = 21) underwent a sigmoid cost-effective but leads to a higher vage based on the potential conse- mean age of the lavage patients was resection; all but one of these oc- reoperation rate and recurrence 66.4 years, and 39 were men. The curred within a year of the index they wrote. mean age of the resection patients procedure, the researchers wrote. sigmoid resection,” the researchers quences“Although of early one maytreatment consider failure, the was 63.5 years, and 36 were men. In addition, overall length of hospi- rate, often requiring secondary need for early reoperation a com- The primary outcome was severe tal stay was similar for both groups. undergoing lavage should have con- plication, some would argue it af- complications – excluding stoma - sentedemphasized. for resection Consequently, surgery. patients fects the minority of patients, thus reversals and elective sigmoid re- ity of life were noted between the The similar rates of severe com- avoiding the more morbid proce- sections because of recurrence – at groups,No significant based on differences the EuroQoL-5D in qual Continued on page 9

plications and quality of life scores

Q1. A 42-year-old male on chronic opiates for history Q2. A 63-year-old female presents with a recent of old spinal injury was seen for dysphagia. The pa- change in bowel habits. She previously had one formed bowel movement a day, but now has diarrhea for the last 1 year without anorexia or weight loss. three to four times a day with incontinence. She had Patienttient reports denies having symptoms dysphagia of heartburn for solids or and regurgita- liquids prior normal colonoscopy 3 years ago. tion. A recent upper endoscopy was unrevealing. A high-resolution esophageal manometry was ordered. Which of the following tests is not indicated as part of this evaluation? Quick Quiz A. CT scan. been shown to be associated with chronic opiate use? A.Which Type of 1 theachalasia. following manometric findings have C. Anorectal manometry. B. Ineffective esophageal motility. D.B. ColonoscopyDigital rectal toexam. evaluate for inflammation. E. Endoanal ultrasound. D. Absent contractibility. C. Esophagogastric junction outflow obstruction. The answers are on page 30.

MDedge.com/gihepnews / August 2021 3

1_3_9_10_20_21_GIHEP21_08.indd 3 7/21/2021 3:23:58 PM B:10.75" T:10.5" S:9.75" S:12.25" B:13.25" T:13"

GIHEP_08.indd 1 7/20/2021 8:51:37 AM FS:9.75" FS:-0.75" F:10.5" F:0"

Cosmos Communications 1 Q1 Q2 K ej 44877a1 07.16.21 133 1 PREPARED BY 11561844 US Branded Journal Ad KING SIZE M4FR Job info Images Fonts Special Instructions Date: 7-12-2021 3:56 PM King Size Brief Summary.pdf (97%; 92KB) None 3 page ad 4/C + 2 single BW Brief Summary Client: BMS pages Product: OZANIMOD US Client Code: None Additional Information WF Issue # None GI and Hepatology News Due 7/15 for Aug, Sept Releasing as: Native Files & Dec issues Final Size: 21" x 13" Gastroenterology & Endoscopy News Due 9/12 for Finishing: None Gutter: None Inks Additional Comments for Sizing Colors: 4/C & B/W Black NOTE: .375" gutter either side = 9.75""wide LIVE AREA per pg. Team Producer: None AD: Phoebe Feliz AE: Leah OKeeffe Scale: 1" = 1" QC: None Bleed 21.25" w x 13.25" h 21.25" w x 13.25" h Production: Debi Post Trim/Flat 21" w x 13" h 21"wx13"h Digital Artist: Schlomann, Greg (PPY-SRX) Live/Safety 20.25" w x 12.25" h 20.25" w x 12.25" h FR Spellcheck: None

Path: PrePress:BMS:OZANIMOD:11561844:_Packaged_Jobs:11561844_US_Branded_Ad_KingSize_M4FR:11561844_US_Branded_Ad_KingSize_M4FR.indd PDFX1A _ †IBD & INTESTINAL DISORDERS Inexpensive dye tracks digestive transit time

BY JIM KLING has gained momentum in recent years, according naire detailing the frequency and consistency MDedge News to Henrik Roager, PhD, who was asked to com- of bowel movements. The researchers also con- ment on the study. “I think it has become clear ducted sequencing of stool samples to determine hen it comes to measuring gut transit that it is probably one of the most important time, blue dye could be a cost-effective factors that explain the [microbiota] differences There was a strong correlation between stool Wand simple alternative to other, more that we see from individual to individual,” said consistencymicrobiome andprofile. frequency, as well as micro- burdensome methods. Dr. Roager, of the department of nutrition, exer- bial diversity and the composition of the gut The approach, which requires only fasting cise, and sports at the University of Copenhagen. followed by eating dyed food, revealed an asso- The relationship is complex, since gut mi- different fast and slow transit time clusters ciation between microbiome composition and crobes may be releasing metabolites that can (areamicrobiome. under the The receiver dye measurement operating characteris- identified transit time in healthy individuals, according affect motility, which in turn would affect the tic curve, 0.82), which were associated with the to authors led by Francisco Asnicar, PhD, of the microbes. composition of the gut microbiome, including University of Trento (Italy) species like Akkermansia muciniphila, Bacteroi- (Gut. 2021 Mar. doi: 10.1136/ des species, and Alistipes species (false discovery gutjnl-2020-323877). The re- rate–adjusted P values < .01). Transit times mea- searchers chose the blue food “I think it has become clear that sured with the blue dye was a better predictor coloring over carmine red dye [transit time] is probably one of the of gut function than either stool consistency and partly because of its vegetable most important factors that explain stool frequency, suggesting that the dye may be a origin and because the blue more useful method for large cohorts of healthy color makes it unlikely the re- the [microbiota] differences that we individuals. cipient would mistake the col- see from individual to individual.” Although associations with diet and car- oring in stool as originating diometabolic factors were more modest, longer from some other food, such as Dr. Roager transit times appear predictive of greater viscer- beetroot. al fat and higher postprandial responses, “which Gut motility is connected to digestion, the Epidemiological studies made easier by dye or are key measures of health.” immune system, the endocrine system, and gut sweet corn could also reveal how diet interacts The authors cited some limitations, including microbiota, according to the authors. For exam- with the microbiome by including transit time as the fact that the blue-dye method has not yet ple, some have suggested that transit time may a variable. Transit time can vary from day to day, been compared with other transit methodolo- affect postprandial glycemia and lipemia through and Dr. Roager believes those variations may be gies. However, the gut transit time in this study a potential effect on nutrient absorption and gut linked to changes in the gut microbiome. With was found to be strongly correlated with stool microbiome composition (Nutrients. 2018 Feb simpler techniques for measuring transit time, “I consistency and frequency. 28;10[3]:275). “[This blue dye’s] use therefore has think we might be able to better identify effects the potential to provide another piece of the puzzle of diets or drugs or lifestyle on the microbiome.” blue dye method is a novel, inexpensive and scal- to advance precision medicine,” the authors wrote. able“To method conclude, of gutour transit findings assessment indicate that providing the Validated methods to measure transit time How the blue dye fared valuable gut health and metabolic insights,” they include scintigraphy, wireless motility capsule, The researchers analyzed data from 866 twins wrote. “Its wide use in both research and clinical radio-opaque markers, and breath testing, but and unrelated adults from the United States and settings could facilitate the advancement of our they require specialized equipment and staff, the United Kingdom who were enrolled in the understanding of gut function and its determi- participants must make at least one in-person - nants, as well as the complex interactions be- visit, and they can be expensive. sponses to standardized meals. Participants un- tween gut physiology and health outcomes.” PREDICT 1 study, which quantified metabolic re The study authors received funding from a Transit time’s position in research along with a glass of chocolate milk, then logged wide range of nonindustry sources. Dr. Roager Those limitations may explain why the effect of derwent fasting and then ate two blue muffins, transit time has been understudied, though it an app. Participants also answered a question- [email protected] the first sign of blue coloring in their stool using had no relevant financial disclosures.

Continued from page 3 Gastroenterologist approach from a patient perspec- include identifying a standardized dure with creation of a stoma at the perspective: Study fills tive is certainly refreshing.” endpoint for lavage, and determining index operation in the majority of gap in follow-up data Dr. Johnson said he was surprised how expanded use of the procedure patients,” they noted. “Additionally, In an interview, David A. Johnson, by how well the patients fared after might impact community practice, patients who underwent lavage that MD, professor of medicine at Eastern lavage given the severity of the di- Dr. Johnson said. In addition, more subsequently proceed to colectomy Virginia School of Medicine, Norfolk, verticulitis in the patient population. research is needed to more clearly would have otherwise been offered said the study is important because However, this may be in part because this therapy initially at the time of data have been lacking on outcomes of the relatively small numbers of from laparoscopic lavage. the index operation.” of laparoscopic lavage without resec- patients at highest risk for complica- defineThe studypatients was most supported likely to in benefit part More research is needed to an- - tions, such as those with diabetes or by the department of surgery at swer questions such as which, if jor shift” in the growing consensus immunocompromising conditions. Skåne University Hospital, Akershus - amongtion. The surgeons findings that represent laparoscopic “a ma Dr. Johnson also said he was University Hospital, and a fellowship ated with failure. In addition, an lavage is a viable option in appro- struck by the fact that the adeno- to one of the study coauthors from any, operative findings are associ priate patients, he said. carcinomas in the lavage group the Southeastern Norway Regional between the two options should be A key issue is the high rate of Health Authority. Lead author Dr. explored,analysis of the long-term authors costwrote. benefits morbidity in patients who undergo year after the procedure. “The can- Azhar disclosed grants from the Based on current evidence, traditional diverticulitis surgery. were diagnosed within the first department of surgery of Skåne Uni- shared decision-making is neces- Complications can include wound the lavage group,” but emphasizes versity Hospital. Dr. Cunninghamm, sary, with individualized care and infection and poor quality of life thecer diagnosisimportance shouldn’t of having reflect an earlier on Dr. Zuckerbraum, and Dr. Johnson short- and long-term trade-offs tak- associated with stoma, Dr. Johnson colonoscopy, he noted. en into account, they wrote. said. Consequently, “a nonoperative Next steps for research might [email protected] had no relevant financial disclosures. MDedge.com/gihepnews / August 2021 9

1_3_9_10_20_21_GIHEP21_08.indd 9 7/21/2021 3:23:59 PM †IBD & INTESTINAL DISORDERS Drug could have ‘profound impact’ - - Celiac from page 1 conditions with minor gluten inges “Although this trial is very en tion,”Translating they concluded. potential couraging, whether treatment researchers assessed the safety into practice with ZED1227, and more generally transglutaminase 2 inhibition, in suggested slight improvements in patients with celiac disease will be and efficacy of three dose levels of symptoms and quality of life for the “An absence of mucosal damage efficient in real life and during long- ZED1227. Adults with controlled 100-mg dose. is a critical criterion to ensure the term gluten exposure remains to be celiac disease were randomized to Findings were limited by several long-term health of a patient, and Needdetermined,” for data Dr. Jabrion concluded. doses of 10 mg (41 patients), 50 factors including missing data and this clinical trial in celiac disease dosing consistency mg (41 patients), and 100 mg (41 loss of several patients to follow-up, meets this important endpoint,” patients), and 40 patients received a “An absence of mucosal Bana Jabri, MD, of the University of placebo. Of these, 35, 39, 28, and 30- Chicago, wrote in an accompanying “Celiac disease affects up to 2% of- patients, respectively, had sufficient damage is a critical criterion editorial (N Engl J Med. 2021 Jun- the population in many countries, duodenal biopsy samples for anal- to ensure the long-term health 30. doi: 10.1056/NEJMe2107502). and the main therapy of celiac dis - ysis. The primary endpoint of no mu - ease is avoidance of gluten,” Kim L. Patients underwent a daily glu of a patient, and this clinical cosal damage is “especially notable Isaacs, MD, PhD, AGAF, of the Univer- ten challenge of 3 g for 6 weeks. trial in celiac disease meets because it was achieved under a con sity of North Carolina, Chapel Hill, At the end of 6 weeks, the primary this important endpoint.” trolled gluten challenge, albeit with a said in an interview. “This is chal study endpoint of attenuation of relatively moderate amount of gluten lenging due to the ubiquitous nature gluten-induced mucosal damage (a regular diet contains 12 g of gluten of gluten in many food products,” - was measured by the ratio of villus daily, whereas the challenge involved she said. “Restrictive eating also height to crypt depth. - 3 g daily) and for a short period of - affects social interaction which is of Patients in all three treatment - time,” Dr. Jabri said. The reduction of ten focused around food,” she added. groups showed significant atten as well as the short trial duration disease-associated symptoms and ap “Availability of an oral therapy that- uation of mucosal damage. The and use of controlled gluten inges - parent improvement in quality of life is effective to treat celiac in the face change in the average ratio of villus tion, the researchers noted. Larger with 100-mg dose added value to the of gluten exposure will have a pro height to crypt depth compared to studies involving real-world condi findings, she said. found impact on patients in terms of placebo in the 10-mg, 50-mg,P and tions of minor gluten ingestion are Future research areas include - liberalization of dietary intake.” 100-mg groups was 0.44, 0.49, and needed to support the preliminary whether cross-reactive T cells, - Overall, “the changes in the villus 0.48, respectively, with values signs of safety and efficacy, they said. which were not analyzed in the cur height to crypt depth was similar equal to .001 in the 10-mg group Study strengths include high- rent study, might “expand and be between all the active treatment and less than .001 in the 50-mg and levels of patient adherence to the come pathogenic after a long-term groups, whereas there was a 100-mg groups. treatment and the gluten chal gluten challenge,” Dr. Jabri noted. - dose-dependent reduction in trans- ­ Adverse events were similar lenge, they said. “Future studies- However, “ZED1227 is the first epithelial lymphocyte density,” Dr. across all treatment groups and the of ZED1227 in more patients are nondietary treatment that has pre Isaacs noted. “The symptom im placebo group, with the exception -of needed to provide additional ev liminarily shown the capacity to provement was greatest in the 100- a rash in three patients in the 100- idence of the safety and efficacy prevent mucosal damage in persons mg group, suggesting that symptoms mg group. A total of 74 patients re of the drug, potentially in real-life with celiac disease,” she said. may be related to a greater extent ported adverse events, and the most to the lymphocyte density than the- common were headache, nausea, minimal differences in villus height diarrhea, vomiting, and abdominal- to crypt depth ratios seen in the ac pain. The investigators determined - tive treatment groups.” that from 34% to 55% of the ad Potential barriers to the use of the verse events across groups were re treatment include cost because “this- lated to the study drug or placebo. will need to be a daily long-term Two patients developed serious- therapy,” said Dr. Isaacs. “Compli adverse events that were deemed ance is a potential barrier as well,” - related to the study drug or place she said. “This study looks at daily bo; one patient in the 50-mg group- administration of the transglutami developed migraine with aura, and nase 2 inhibitor and shows a benefit, one placebo patient developed ven but it is not clear whether missing tricular extrasystoles. The patients doses of the medication will have a recovered after discontinuing the prolonged impact on efficacy,” she drug or placebo. emphasized. Consequently, long- s e

Secondary endpoints included g term efficacy studies are needed, Dr. ma I

intraepithelial lymphocyte density,- Isaacs said. Other research questions-

the Celiac Symptom Index score, etty to answer include whether patients

and the Celiac Disease Question /G will become refractory to the bene naire score. Estimated changes in ficial effects over time, the effect of ibrary L intraepithelial lymphocyte density, missing doses, and whether patients

compared with placebo, were –2.7 hoto would lose all the benefits of the cells per 100 epithelial cells in the P therapy if dosing is not consistent,

10-mg group, −4.2 cells per 100 cience she emphasized. /S i epithelial cells in the 50-mg group,- k The study was funded by Dr. Falk

and −9.6 cells per 100 epithelial aulitz Pharma. The researchers, as well cells in the 100-mg group. Com K as Dr. Jabri and Dr. Isaacs, had no tian pared with those of patients taking s financial conflicts to disclose. Dr. eba

placebo, the 6-week changes in S Isaacs is on the [email protected] advisory Celiac Symptom Index scores and board of GI & Hepatology News. Celiac10 Disease Questionnaire scores August 2021 / GI & Hepatology News

1_3_9_10_20_21_GIHEP21_08.indd 10 7/21/2021 3:24:02 PM †IN FOCUS: MICROSCOPIC COLITIS Microscopic colitis: A common, yet often overlooked, cause of chronic diarrhea

BY JUNE TOME, MD; for chronic diarrhea. Since MC is AMRIT K. KAMBOJ, MD; AND now well recognized, the recent DARRELL S. PARDI, MD, MS, AGAF plateau in incidence rates may re-

icroscopic colitis is an in- The prevalence of MC ranges fromflect decreased10% to 20% detection in patients bias. un- colon and a frequent cause dergoing colonoscopy for chronic M 6,7 of chronicflammatory or recurrent disease watery of diar-the watery diarrhea. The prevalence rhea, particularly in older persons. of LC is approximately 63.1 cases MC consists of two subtypes, collag- per 100,000 person-years and, for enous colitis (CC) and lymphocytic CC, is 49.2 cases per 100,000 per- colitis (LC). While the primary son-years.6-8 Recent studies have symptom is diarrhea, other signs demonstrated increasing preva- and symptoms such as abdominal lence of MC likely resulting from an Dr. Tome is with the department of internal medicine at the Mayo Clinic, pain, weight loss, and dehydration aging population.9,10 Rochester, Minn. Dr. Kamboj and Dr. Pardi are with the division of gastro- or electrolyte abnormalities may enterology and hepatology at the Mayo Clinic. Dr. Pardi has grant funding also be present depending on dis- Risk stratification from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda ease severity.1 In MC, the colonic Female gender, increasing age, con- and has consulted for Vedanta and Otsuka. The other authors have no con- mucosa usually appears normal comitant autoimmune disease, and flicts of interest to report. on colonoscopy, and the diagnosis the use of certain drugs, including NSAIDs, proton pump inhibitors intraepithelial lymphocytosis with (PPIs), statins, and selective sero- 1.63; 95% CI, 1.37-1.94, respective- tients with CD who consume gluten; (CC)is made or without by histologic (LC) afindings prominent of tonin reuptake inhibitors (SSRIs), ly), compared with nonsmokers.17 however, large population-based subepithelial collagen band. The have been associated with an in- Smokers develop MC at a younger - management approaches to CC and creased risk of MC.11,12 Autoimmune age, and smoking is associated etary associations with the develop- LC are similar and should be direct- disorders, including celiac disease with increased disease severity and mentstudies of haveMC.22 not found specific di ed based on the severity of symp- (CD), rheumatoid arthritis, hypothy- decreased likelihood of attaining Another potential mechanism of toms.2 We review the epidemiology, roidism, and hyperthyroidism, are remission.18,19 MC is dysregulated collagen depo- risk factors, pathophysiology, diag- more common in patients with MC. sition. Collagen accumulation in the nosis, and clinical management for The association with CD, in partic- Pathogenesis subepithelial layer in CC may result this condition, as well as novel ther- ular, is clinically important, as CD is The pathogenesis of MC remains - apeutic approaches. associated with a 50-70 times great- largely unknown, although there blast growth factor, transforming er risk of MC, and 2%-9% of patients are several hypotheses. The leading growthfrom increased factor–beta levels and of vascularfibro Epidemiology with MC have CD.13,14 proposed mechanisms include re- endothelial growth factor.23 None- Although the incidence of MC in- Several medications have been action to luminal antigens, dysregu- theless, studies have not found an creased in the late 20th century, associated with MC. In a British lated collagen metabolism, genetic association between the severity more recently, it has stabilized with multicenter prospective study, MC predisposition, autoimmunity, and of diarrhea in patients with CC and an estimated incidence varying was associated with the use of bile acid malabsorption. the thickness of the subepithelial from 1 to 25 per 100,000 per- NSAIDs, PPIs, and SSRIs15; howev- MC may be caused by abnormal collagen band. son-years.3-5 A recent meta-analy- er, recent studies have questioned epithelial barrier function, leading Thirdly, autoimmunity and ge- sis revealed a pooled incidence of the association of MC with some to increased permeability and reac- netic predisposition have been pos- 4.85 per 100,000 persons for LC of these medications, which might tion to luminal antigens, including tulated in the pathogenesis of MC. and 4.14 per 100,000 persons for worsen diarrhea but not actually dietary antigens, certain drugs, and As previously discussed, MC is as- CC.6 Proposed explanations for the cause MC.16 bacterial products,20,21 which them- sociated with several autoimmune rising incidence in the late 20th An additional risk factor for MC selves lead to the immune dysregu- diseases and predominantly occurs century include improved clinical is smoking. A recent meta-analysis in women, a distinctive feature of awareness of the disease, possible demonstrated that current and for- seen in MC. This mechanism may autoimmune disorders. Several increased use of drugs associated mer smokers had an increased risk explainlation and the intestinal association inflammation of several studies have demonstrated an asso- with MC, and increased perfor- of MC (odds ratio, 2.99; 95% con- drugs with MC. Histological changes ciation between MC and HLA-DQ2 mance of diagnostic colonoscopies resembling LC are reported in pa- Continued on following page

icroscopic colitis is a cause of chronicfidence or interval, recurrent 2.15-4.15 watery diarrheaand OR, written by Dr. June Tome, Dr. Amrit K. Kamboj, and Dr. Mthat occurs more commonly in women, older individuals, or those Darrell S. Pardi (Mayo Clinic, Rochester, Minn.). This article describes the risk factors, pathogenesis, and NSAIDs, proton pump inhibitors, and selective serotonin uptake inhibi- diagnosis of the disease. Importantly, the authors also torswith mayconcomitant trigger symptoms. autoimmune Diagnosis diseases. can Specific be elusive medications as colonic such mucosa as elucidate a comprehensive management approach, - which can be challenging given the frequently relaps- ings are histologic. ing and remitting nature of its clinical course. typicallyThe In Focusappears article endoscopically for August, normal, which is and brought the pathognomonic to you by The Newfind Vijaya L. Rao, MD Gastroenterologist, provides a detailed review on microscopic colitis Editor in Chief, The New Gastroenterologist

MDedge.com/gihepnews / August 2021 11

11_to_15_GIHEP21_08.indd 11 7/21/2021 3:42:55 PM Continued from previous page nosuppression, should be obtained 24 • Initial • Mild to

and -DQ3 haplotypes, as well as in patients with chronic diarrhea. di steps moderate ar

potential polymorphisms in the Additionally, laboratory and en- P . S serotonin transporter gene promot- doscopic evaluation with random Loperamide symptoms er. 25 It is important to note, howev- biopsies of the colon can further Discontinue arrell

offending and/or D er, that only a few familial cases of help differentiate these diseases . 26 r MC have been reported to date. from MC. A few studies suggest medications D Bismuth d an

Lastly, bile acid malabsorption fecal calprotectin may be used to ,

Smoking cessation subsalicylate j may play a role in the etiology of differentiate MC from other non- - ambo K K.

mation, along with villous atrophy irritable bowel syndrome, as well t i

andMC. Histologiccollagen deposition, findings of have inflam been asinflammatory to monitor diseaseconditions activity. such Thisas mr A

Consider other . reported in the ileum of patients test is not expected to distinguish r

causes of diarrhea D 27,28 , with MC ; however, because (e.g., celiac disease) Budesonide* ome T

patients with MC without bile acid of diarrhea, such as IBD, and there-

malabsorption may also respond to fore,MC from its role other in clinicalinflammatory practice causes is Immunotherapy une J

• Moderate . bile acid binders such as cholestyr- uncertain.31 • Refractory r to severe D The diagnosis of MC is made symptoms the sole mechanism explaining the by biopsy of the colonic muco- symptoms ourtesy devamine,elopment these findings,of the disease. unlikely to be sa demonstrating characteristic C 32 Despite the different proposed pathologic features. *Budesonide should be considered for induction and maintenance therapy, mechanisms for the pathogenesis of diseases such as Crohn’s disease or if necessary, to control patient symptoms. ulcerative colitis, the colon Unlike usually in drawn because of the limited size of appears normal in MC, although Figure 2: Management approach to microscopic colitis is charted. theseMC, no studies definite and conclusions their often can con- be erythema or edema, may be visual- patients. A stepwise pharmacolog- ized.mild nonspecificThere is no consensuschanges, such on theas band greater than 7-10 microme- ical approach is used in the man- Clinicalflicting results. features ideal location to obtain biopsies for tersa thickened (normal, subepithelial less than 5) collagen(Figure agement of MC based on disease Clinicians should suspect MC in pa- MC or whether biopsies from both 1B). For a subgroup of patients with severity (Figure 2). For patients tients with chronic or recurrent wa- the left and the right colon are re- milder abnormalities that do not with mild symptoms, antidiarrheal tery diarrhea, particularly in older quired.2,33 The procedure of choice meet these histological criteria, the medications, such as loperamide, for the diagnosis of MC is colonos- terms “microscopic colitis, not oth- may be helpful.36 Long-term use of female gender, use of certain culprit loperamide at therapeutic doses no persons. Other risk factors include- throughout the colon. More limited 35 greater than 16 mg daily appears ence of other autoimmune diseases. copy with random biopsies taken - erwiseThese patients specified” often or “microscopicrespond to to be safe if required to maintain Themedications, clinical manifestations smoking, and presof MC py with biopsies may miss cases of colitis,standard incomplete” treatments may for beMC. used. There symptom response. For those with subtypes LC and CC are similar with evaluation by flexible sigmoidosco is an additional subset of patients persistent symptoms despite an- 1,2 - with biopsy demonstrating features tidiarrheal medications, bismuth In addition to diarrhea, patients formMC as throughout inflammation the andcolon; collagen howev- of both CC and LC simultaneously, subsalicylate at three 262-mg tab- withno significant MC may haveclinical abdominal differences. pain, er,thickening in a patient are thatnot necessarily has undergone uni a as well as patients transitioning fatigue, and dehydration or elec- recent colonoscopy for colon cancer from one MC subtype to another can be considered. Long-term use trolyte abnormalities depending on screening without colon biopsies, over time.32,35 oflets bismuth three times subsalicylate daily for is6-8 not weeks disease severity. Patients may also advised, especially at this dose, be- present with fecal urgency, inconti- a reasonable next test for evalua- Management approach cause of possible neurotoxicity.37 nence, and nocturnal stools. Quality tiona flexible of MC, sigmoidoscopy provided biopsies may arebe For patients refractory to the of life is often reduced in these pa- obtained above the rectosigmoid patients with MC includes stopping above treatments or those with tients, predominantly in those with colon.34 culpritThe first medications step in management if there is ofa moderate to severe symptoms, an severe or refractory symptoms.29,30 The MC subtypes are differentiat- temporal relationship between the The natural course of MC is highly initiation of the medication and the - variable, with some patients achiev- of LC is less than 20 intraepithelial onset of diarrhea, as well as en- ment.8-week38 courseThe dose of budesonidewas tapered at ing spontaneous resolution after lymphocytesed based on histology. per 100 surface The hallmark ep- 9befor mg edaily discontinuation is the first-line in sometreat one episode and others developing ithelial cells (normal, less than 5) studies but not in others. Both chronic symptoms. (Figure 1A). CC is characterized by achievecouraging clinical smoking remission cessation. in most These Continued on page 14 steps alone, however, are unlikely to Diagnosis The differential diagnosis of chron- ic watery diarrhea is broad and c

includes malabsorption/maldiges- i n i l C

(IBD), irritable bowel syndrome, ayo M andtion, medication inflammatory side bowel effects. disease In ad- /

dition, although gastrointestinal agen H

ne

infections typically cause acute or i subacute diarrhea, some can pres- ather C

ent with chronic diarrhea. Malab- . r

sorption/maldigestion may occur D because of CD, lactose intolerance, courtesy other conditions. A thorough histo- mages ry,and regarding pancreatic recent insufficiency, antibiotic among and I medication use, travel, and immu- Figure 1A: Histopathology is shown for lymphocytic colitis. Figure 1B: Histopathology is shown for collagenous colitis.

12 August 2021 / GI & Hepatology News

11_to_15_GIHEP21_08.indd 12 7/21/2021 5:10:34 PM GIHEP_13.indd 1 7/14/2021 4:06:36 PM Continued from page 12 medication considered in the use mesalamine in this setting, sociation recommends budesonide strategies appear effective. A recent management of MC and warrants although mesalamine is inferior to for maintenance of remission in meta-analysis of nine randomized further investigation. To date, no budesonide in the induction of clin- patients with recurrence following trials demonstrated pooled ORs of randomized clinical trials have ical remission in MC.40 discontinuation of induction ther- 7.34 (95% CI, 4.08-13.19) and 8.35 been conducted to evaluate bile Despite high rates of response to apy. The lowest effective dose that (95% CI, 4.14-16.85) for response acid sequestrants in MC, but they budesonide, relapse after discontin- maintains resolution of symptoms to budesonide induction and main- should be considered before plac- uation is frequent (60%-80%), and should be prescribed, ideally at tenance, respectively.39 ing patients on immunosuppres- time to relapse is variable.41,42 The 6 mg daily or lower.38 Although Cholestyramine is another sive medications. Some providers American Gastroenterological As- metabolism, compared with other glucocorticoids,budesonide has apatients greater should first-pass be monitored for possible side effects including hypertension, diabetes, and osteoporosis, as well as oph- thalmologic disease, including cata- racts and glaucoma. For those who are intolerant to budesonide or have refractory symptoms, concomitant disorders such as CD that may be contribut- ing to symptoms must be excluded. Immunosuppressive medications – such as thiopurines and biologic agents, including tumor necrosis factor–alpha inhibitors or vedol- izumab – may be considered in refractory cases.43,44 Of note, there are limited studies evaluating the use of these medications for MC. Lastly, surgeries including ileosto- my with or without colectomy have been performed in the most severe cases for resistant disease that has failed numerous pharmacological therapies.45 Patients should be counseled that, while symptoms from MC can be quite bothersome and disabling, there appears to be a normal life expectancy and no association be- tween MC and colon cancer, unlike

of the colon such as IBD.46,47 with other inflammatory conditions Conclusion and future outlook As a common cause of chronic wa- tery diarrhea, MC will be commonly encountered in primary care and gastroenterology practices. The diagnosis should be suspected in patients presenting with chronic or recurrent watery diarrhea, especial- ly with female gender, autoimmune disease, and increasing age. The management of MC requires an algorithmic approach directed by symptom severity, with a subgroup of patients requiring maintenance therapy for relapsing symptoms. The care of patients with MC will continue to evolve in the future. Further work is needed to explore long-term safety outcomes with budesonide and the role of immu- nomodulators and newer biologic agents for patients with complex, refractory disease.

See references at MDedge.com/ gihepnews/new-gastroenterologist.

14 August 2021 / GI & Hepatology News

11_to_15_GIHEP21_08.indd 14 7/21/2021 3:43:00 PM NEWS FROM THE AGA New Clinical Practice Update Expert Review: Management of bleeding gastric varices

GA has released a new Clin- • - ical Practice Update Expert apy for bleeding gastric varices AReview providing 12 best shouldDetermination be based of on definitive endoscopic ther practice advice statements on the appearance of the gastric varix, diagnosis and management of the underlying vascular anato-

bleeding gastric varices. The evi- my, presence of comorbid portal mages I y

dence-based advice includes the hypertensive complications, and tt e G following: available local resources. This / • Initial therapy for bleeding gas- is ideally done via a multidisci- mages I

tric varices should focus on acute plinary discussion between the GI ra t e

hemostasis for hemodynamic or hepatologist and the interven- T stabilization with a plan for fur- tional radiologist. ther diagnostic evaluation and/or In this AGA Clinical Practice Up- transfer to a tertiary care center date Expert Review, the experts Five reasons to update with expertise in gastric varices also suggest adding an estimate of management. • Following initial endoscopic he- your will mostasis, cross-sectional (mag- variceal size and high-risk stigmata- netic resonance or CT) imaging scribing(discolored patients’ marks, gastric platelet varices. plugs) ou have a will, so you can rest laws among the states vary. Mov- with portal venous contrast phase toRead the Sarin the full classification list of the best when practice de Yeasy, right? Not necessarily. If ing to a new state or purchasing should be obtained to determine advice statements in the AGA Clini- your will is outdated, it can actu- property in another state can vascular anatomy, including the cal Practice Update on Management ally cause more harm than good. affect your estate plan and how presence or absence of porto- of Bleeding Gastric Varices: Expert Even though it can provide for property in that state will be systemic shunts and gastrorenal Review (Clin Gastroenterol Hepatol. some contingencies, an old will taxed and distributed. shunts. 2021 Jun;19[6]:1098-107.e1). can’t cover every change that may • Changes in your estate’s value. When you made your will, your assets may have been relatively updatehave occurred your will. since it was first modest. Now the value may be drawn. Here are five reasons to larger and your will no longer Keep it current When life changes, so should your estate divided. will. Ensure that this important • Taxreflects law howchanges. you wouldFederal like and your document matches your current state legislatures are continually wishes by reviewing it every few mages I

y years. state inheritance tax laws. An tt e

G tinkering with federal estate and- / Take a look at what tage of strategies that will mini-

amera mizeold will estate may taxes. fail to take advan C has changed t a

F Professionals advise that you • You want to support a favorite review your will every few years cause. If you have developed a and more often if situations connection to a cause, you may

AGA journals select new occurred since you last updated charity with a gift in your es- suchyour aswill. the following five have wanttate. Contact to benefit us afor particular sample lan- editorial fellows • Family changes. If you’ve had guage you can share with your any changes in your family situ- attorney to include a gift to us he AGA journals Gastroenterol- in its fourth year. ation, you will probably need to in your will. Togy, Clinical Gastroenterology • Amisha Ahuja, MD (Gastroenter- update your will. Events such as and Hepatology (CGH), Cellular ology) marriage, divorce, death, birth, Get the help you need and Molecular Gastroenterology • - adoption, or a falling out with a - and Hepatology (CMGH), and Tech- terology) loved one may affect how your niques and Innovations in Gastroin- • KatherineHelenie Kefalalkes, Falloon, MDMD (CGH)(Gastroen estate will be distributed, who helpTo make of an sure attorney your willwho accom special- testinal Endoscopy (TIGE) recently • Judy Trieu, MD, MPH (CGH) should act as guardian for your izesplishes in estate all you planning. intend, seek Already the selected the recipients of their edi- • Lindsey Kennedy, PhD (CMGH) dependents, and who should - torial fellowships, which runs from • Vivian Ortiz, MD (CMGH) be named as executor of your tion to the AGA Research Founda- July 2021 through June 2022. The • estate. tion?finalized Send your us yourcharitable letter distribuof intent AGA editorial fellowship program is • Eric Swei, MD (TIGE) • Relocating to a new state. The at [email protected]. Sagarika Satyavada, MD (TIGE) MDedge.com/gihepnews / August 2021 15

11_to_15_GIHEP21_08.indd 15 7/21/2021 3:43:05 PM †OBESITY Best practices: Consider endoscopy first a surgeon present (preferably the surgeon who Complications from page 1 performed the operation).” gery is unmatched with respect to its weight loss propagateDr. Kumbhari leaks. and They colleagues noted that discussed “downstream functional stenosis, which can precipitate and in Clinical Gastroenterology and Hepatology Following these best practices, Dr. Kumbhari incisura angularis or in the proximal stomach (2021and metabolic Mar 16. benefits,”doi: 10.1016/j.cgh.2021.03.020). the investigators wrote bothand colleagues medical in advised nature (suchscreening as infection) patients andwith stenosis is frequently seen at the level of the - psychological.postoperative complications for comorbidities, tient with a prior laparoscopic adjustable gastric likely resulting in increasing numbers of less ro- when a sleeve gastrectomy is performed in a pa “The selection criteria will continue to broaden, - band.” bust patients undergoing surgery (e.g., children, To address such stenosis, the update calls for elderly, and those with significant cardiorespira sure“aggressive the distal dilation” end of using the balloon a large does pneumatic not cross ratetory acrosscomorbidities).” all patients undergoing bariatric/ balloon, preferably with fluoroscopy to make - Although the 90-day overall complication colleagues noted that this rate is considerably the muscularispylorus. The propria investigators is encountered. noted that endo metabolic surgery is only 4%, Dr. Kumbhari and scopic suturing may be needed if a tear involving- 65 years.

higher, at 20.1%, among patients aged older than ource Lastly, the clinical practice update offers com S

ce prehensive guidance for managing staple-line n e i

wrote.“As utilization escalates, so will the number of c leaks, which “most commonly occur along the S / s

patients who suffer early complications,” they n “moststaple leaksline of are the not proximal present stomach.” upon completion of o i t

describe who should be managing complications a As leaks are thought to stem from ischemia, - The first three items of best practice advice llustr

I the operation, and they develop over the subse

forafter a multidisciplinarybariatric/metabolic approach; surgery, they and how.suggest- DNA quent weeks, often in the setting of downstream edForemost, that endoscopists Dr. Kumbhari should and work colleagues closely withcalled stenosis,” the investigators wrote. To guide management of staple-­line leaks, the - andinvestigators presence presentedor absence a oftreatment stenosis. algorithm related“Timely specialists, communication such as betweenbariatric/metabolic the endosco- “Patients often have higher depression and that incorporates defect size, time since surgery,- surgeons and interventional radiologists. - anxiety scores, as well as a lower physical qual curring within 6 weeks of surgery and lacking patient medical team or primary care physician ity of life, and medical teams sometimes neglect stenosisFor example, may be a managed defect smaller with athan percutaneous 10 mm oc pist, radiologist, surgeon, nutritionists, and in recognizethe patient’s and psychological acknowledge state,” the patient’s they wrote. psy- - chological“It is imperative comorbidities that the multidisciplinaryand engage expertise team to will result in efficient, effective care with prompt drain and diversion. In contrast, a defect of sim escalation and deescalation,” they wrote. “Daily shouldilar size, be also managed without with stenosis, endoscopic but occurring internal encouragecommunication high familiarityis advised.” with endoscopic manage them.” later than 6 weeks after the initial procedure, The next two best practice advice statements Next, the investigators advised that endoscopic- “Clinicians should recognize that the goal for intervention should be considered regardless of endoscopicdrainage or managementvacuum therapy. of staple-line leaks is treatments, postsurgical anatomy, interventional time“Endoscopy interval since is often surgery, indicated including as the the initial imme often not necessarily initial closure of the leak radiology, and surgical interventions, including diate postoperative period. - risks and benefits of each approach. of material from the perigastric collection into “The endoscopist should ... have expertise in - thetherapeutic update. modality, and it can safely be per thesite, gastric but rather lumen techniques such that to the promote leak site drainage closes interventional endoscopy techniques, including formed,” Dr. Kumbhari and colleagues wrote in but not limited to using concomitant fluorosco colleagues. py, stent deployment and retrieval, pneumatic “When endoscopy is performed, it is advised byThe secondary clinical intention,”practice update wrote was Dr. commissionedKumbhari and balloon dilation, incisional therapies, endoscopic to use carbon dioxide for insufflation. Caution - performsuturing, a and wide managing array of percutaneoustherapies will drains,”enhance pressureshould be along used thewhen fresh advancing staple lines. the endoscope In cases the likelihoodinvestigators that wrote. the optimal “Having endoscopic the ability strat-to ininto which the small the patient bowel, is as critically it is best ill to or minimize the inter- and approved by the AGA Institute Clinical Prac - tice Updates Committee and the AGA Governing- Board. The investigators disclosed relationships egy will be employed, as opposed to simply per shouldventional be endoscopistperformed in does the notoperating have extensive room with with Boston Scientific, Medtronic,[email protected] Apollo Endo forming a technique with which the endoscopist experience with such a scenario, the endoscopy surgery, and others. has experience.” Semaglutide boosts weight loss following endoscopic gastroplasty

BY PAM HARRISON new research shows. ® comorbidities or a BMI of at least “We found that by adding the ESG is a surrogate for laparoscop- FROM DDW 2021 Disease Week (DDW). 40 if they do not have any. C GLP-1 agonist [semaglutide], we ic sleeve gastrectomy that can offer whoThe also Brazilian had diabetes study involved and were 58 withombining a weekly minimally injection of invasive the glu- couldbody weightincrease with weight ESG lossalone from, to up on the benefits of such a procedure to patients with obesity or overweight cagonlikeendoscopic peptide–1 sleeve agonist gastroplasty sema- average, about 16%-18% of total Itthose can whobe performed don’t qualify at an for, earlier or don’t they were further randomized to glutide wish to pursue, bariatric surgery. undergoing minimally invasive ESG; to 27%, so it’s a great metabolic - body mass index of 30 mg/kg2 loss than (Ozempic, ESG alone Novo in patients Nordisk) with rectorcombination,” of Angioskope said Anna Brazil Carolina in São whereasstage of disease, generally in peoplethose with are nota receive semaglutide or placebo. - diabetesleads to significantly and excess weight greater who weight are Hoff, MD, founder and clinical di offered bariatric procedures unless, Twelve months after ESG, patients not candidates for bariatric surgery who receivedContinued additional on semaglufollowing page José dos Campos, who presented tide lost 86.3% of their excess body 20 , the findings at the annual Digestive they have a BMI of at least 35 withAugust 2021 / GI & Hepatology News

1_3_9_10_20_21_GIHEP21_08.indd 20 7/21/2021 3:24:04 PM †GI ONCOLOGY

standing dietary recommendations The signature could be used as Modifiable risk meets biology will remain unchanged. a biomarker to detect exposure to Link from page 1 “This study will not alter current NOCs, and susceptibility to CRC, she diet recommendations to limit in- added. Institute and Harvard Medical School, occur early in the path of colorectal take of red and processed meats,” Still, Dr. Thompson-Carino sug- both in Boston, and colleagues. carcinogenesis.” Dr. Wu said, referring to similar gested that more work is needed to “Red meat consumption has been Further analysis showed that tu- recommendations across several fully elucidate underlying mecha- consistently linked to the incidence mors harboring common KRAS and organizations, including the Amer- nisms of action, which are needed to of colorectal cancer,” the investi- PIK3CA driver mutations had the ican Heart Association, the World accurately shape dietary guidance. gators wrote in Cancer Discovery highest levels of alkylating damage, Cancer Research Fund/American (2021 Jun 17. doi: 10.1158/2159- with higher levels predicting worse Institute for Cancer Research, and 8290.CD-20-1656). “The suggested survival. the American Cancer Society. AGA Resource mechanism is mutagenesis through “These results ... further implicate “For example,” Dr. Wu said, “the Help your patients understand alkylating damage induced by N-ni- the role of red meat in CRC initia- WCRF/AICR recommends limiting colorectal cancer prevention troso-compounds (NOCs), which tion and progression,” the investiga- consumption of red and processed and screening options by shar- are metabolic products of blood tors concluded. meat to ‘no more than moderate ing AGA’s patient education heme iron or meat nitrites/nitrates. amounts [12-18 ounces per week] from the GI Patient Center: Nevertheless, this mutational dam- Early findings, important of red meat, such as beef, pork, and www.gastro.org/CRC. age is yet to be observed directly in implications lamb, and [to] eat little, if any, pro- patients’ tumors.” Co–senior author Kana Wu, MD, To this end, the investigators PhD, principal research scientist in “Key to advancing red meat di- turned to three long-term, large- the department of nutrition at Har- Possiblecessed meat.’ ” biomarker? etary recommendations will be scale, prospective cohort studies: the vard School of Public Health, Boston, According to Patricia Thompson-­ understanding the relationships Nurses’ Health Studies I and II, and Carino, PhD, deputy director of the between the new mutation signa- the Health Professionals Follow-Up although they may pave the way to- Stony Brook (N.Y.) Cancer Center, ture and the NOCs derived from Study. These databases include wardnoted new that dietarythese are recommendations early findings, the study provides convincing ev- red meat and their source, whether nearly 300,000 individuals with fol- and methods of food production. idence linking red meat consump- endogenous [for example, intestinal low-up dating back as far as 1976. “While more detailed analysis tion with development of CRC. N-nitrosation] or exogenous [for - needs to be conducted, and our re- “Higher frequency of the sig- example, chemical preservation or es of primary, untreated CRC with nature in the distal colon is com- charring],” she said. adequateThe investigators tissue for identified analysis, 900 then, cas studies, this study is a promising pelling for its consistency with The study was supported by for each case, performed whole-­ sults need to be confirmed in other epidemiologic evidence,” Dr. the National Institutes of Health, exome sequencing on both tumor biological mechanisms underlying Thompson-Carino said in an inter- the Stand Up To Cancer Colorectal tissue and normal colorectal tissue. thefirst role step of to red better and understandprocessed meats the view. “Combined with the observed Cancer Dream Team Translational This revealed an alkylating mu- in colorectal cancers,” Dr. Wu said worse survival in patients harbor- Research Grant (coadministered by tational signature previously unde- in an interview. “It is important to ing the signature and association the American Association for Can- gain more insight into the biological with oncogenic KRAS and PIK3CA cer Research), the Project P Fund, associated with consumption of mechanisms so we can improve di- - and others. The investigators, Dr. redscribed meat in prior CRC thatto diagnosis, was significantly but not etary guidelines for cancer preven- cantly elevates the biological plausi- Wu, and Dr. Thompson-Carino re- other dietary or lifestyle factors. The tion and guide food reformulation driver mutations, this study signifi - signature occurred most frequently efforts to lower cancer risk.” source of NOC mutagenicity and ed to this study. in tumors and normal crypts in the For now, Dr. Wu predicted that carcinogenesisbility that red meat in humans.” is a modifiable ported no conflicts [email protected] interest relat distal colon and rectum. According to the investigators, the presence of the alkylating sig- nature in normal colorectal crypts “suggests that mutational changes due to such damage may start to #CCCongress22

LIVE + ON-DEMAND Continued from previous page ® weight – the amount of weight pa- CROHN’S & COLITIS CONGRESS tients needed to lose to reach normal BMI – compared with only 60.4% for JANUARY 20–22, 2022 • LAS VEGAS

percentage total body weight loss at theESG end controls. of 12 Specifically,months was the 25.2% mean for those in the combination group, com- TRANSFORMING IBD CARE pared with 18.6% for those treated with ESG alone (P < .001). Patients in the combination group Register by November 3 lost 12.6% of their body fat mass, and save up to $150. compared with 9% for ESG controls. Abstract submissions are combination group reverted to a non- due October 20. diabeticAdditionally, state five and patients were able in theto dis- continue antidiabetic medications. Dr. Hoff has reported no relevant To learn more and register, visit www.crohnscolitiscongress.org

[email protected] financial relationships. MDedge.com/gihepnews / August 2021 21

1_3_9_10_20_21_GIHEP21_08.indd 21 7/21/2021 3:24:06 PM †FROM THE AGA JOURNALS Network meta-analysis ranks first-line H. pylori regimens

BY JIM KLING MDedge News ment is now needed and that the network meta-analysis [oftime H. for pylori transitioning from trial and wroteerror to antimicrobial stewardship A - infection] has arrived,” apies forof Helicobactercurrent first-line pylori dual, infec- Theodore Rokkas, PhD, MD, triple, and quadruple ther AGAF, of the European University- of Cyprus in Engomi, and colleagues. tion found that vonoprazan triple Their study was published in Gas therapy was most effective, while- troenterologyH. pylori (2021. doi: 10.1053/j. standard triple therapy of a proton gastro.2021.04.012). - pump inhibitor (PPI), amoxicil infection is the primary lin, and clarithromycin was least- cause of gastritis, peptic ulcer dis effective (Turk J Gastroenterol. ease, gastric mucosa–associated 2019 May;30[5]:420-35). Levo - lymphoidSince H. tissuepylori lymphoma, and Learn how to get floxacin-containing triple therapy gastric cancer. - performed best in Western coun infection was first your piece of the tries and West Asia, while reverse recognized, physicians have em hybrid therapy was most effective ployed a range of drugs in double, in East Asia. H. pylori treat- triple, and quadrupleContinued on combinations following page research funding pie. The results “[suggest that] a new to combat it. approach concerning Specialty awards I Applications due July 21 n this perspective, the network in each single patient, revealing Two awards support projects focused on meta-analysis by Rokkas and rates for resistance to macrolides colleagues is very important: The and fluoroquinolones of around digestive cancers. purpose of this study is not only 20%. (Cost-effectiveness advice: to identify those regimens with Take only those biopsy specimens Pilot research awards the highest treatment- success that have turned to be positive in Applications due Aug. 26 in comparison but also- the rapid urease test - stratify for world re and send them in for Awards provide $30,000 for projects in health gions and time-shift as polymerase chain reac care disparities, technology and innovation, pects. The key value of tion testing within 72 the network approach,- hours; 90% success.) colorectal cancer and IBD. however, is the ability In this perspective, - for indirect compari with currently sparse- Research Scholar Awards sons, as presented here. vonoprazan data limit Applications due Nov. 10 With use of the surface- ed to Japan, I still pre- under the cumulative Dr. Treiber fer to go primarily for Awards provide $300,000 to early career ranking values, vono the non–bismuth qua researchers, including those from groups prazan-based triple druple therapy (56 pills therapy may be the to be taken in 1 week), underrepresented in medicine. most promising candidate for the and from my own published data, future, non–bismuth quadruple this regimen will still work if - Summer Undergraduate Research and R-hybrid therapies are also taken for only 5 days. Vice versa,- Fellowship Applications due Jan. 2022 suitable. - in the presence of macrolide re So what is the take-home sistance, amoxicillin allergy, pre Six positions offer undergraduate students from message from this paper? Unfor vious treatment failures, I go for underrepresented groups a glimpse tunately, the authors could not the bismuth quadruple therapy include data concerning drug - – if I can expect good treatment- into GI research. dosage and resistance. I think that compliance because proton pump emphasizing the need for anti inhibitor plus potassium, metro Learn more and apply at usbiotic to still stewardship rely on local on oneresistance hand nidazole, and tetracycline for 10 gastro.org/research-funding. and – at the same time – telling Gerharddays can G.mean Treiber, 140 MD,pills. AGAF, is with the department of internal routinelyknowledge monitors (whatever Helicobacter this means) medicine at Saarland University pyloriis not enough in 2021. Our unit- Hospital, Homburg, Germany. He RSH21-002 has no conflicts of interest. resistance with a poly merase chain reaction technique 22 August 2021 / GI & Hepatology News

22_to_27_GIHEP21_08.indd 22 7/21/2021 3:46:21 PM †FROM THE AGA JOURNALS Tofacitinib in UC: Watch out for herpes zoster reactivation, thrombosis

BY JIM KLING often an anti–tumor necrosis factor–alpha agent P - MDedge News tion between concomitant steroid use and adverse (63.4% vs 79.8%; = .03). There was no associa n a real-world test, tofacitinib had a similar safety (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) events on univariate analysis. Of the overall cohort,- Imajority of adverse events seen were infections, and rash (3.5%). Joint pain (1.5%) and anemia - 5.8% experienced a severe adverse event, with the profile to what was seen in clinical trials. The verse(1.5%) events also occurred. occurred Themore incidence often in rateolder for patients any most common being HZ rash (26.7% of severe ad- adverse event was 27.2 per P100 person-years. Ad verse events). Therapy was discontinued by 4.6%. inand patients few were with serious; preexisting however, risk thefactors, study which did find sug- Five patients developedContinued HZ (3.29 on per following 100 per page evidence of rare venous thromboembolism (VTE) (mean age, 42 vs. 37 years; = .02) and those who son-years; 95% confidence interval, 1.37-7.90). - had not undergone previous anti-TNF therapy provedgests that by precaution the Food and is warranted Drug Administration in this group. ofacitinib is an oral small molecule that of recombinant zoster vaccine before initiating in Tofacitinib,2018 for adults a Janus with kinase moderate inhibitor, to severe was ap Treceived approval by the Food and Drug trials and an open-label, long-term extension most safety data have been derived tofacitinib. trialulcerative found colitis that the (UC). drug Three was phaseassociated 3 clinical with in- fromAdministration clinical trials in December or past marketing 2019. To date, The second adverse event of interest was anVTE. interim The risk analysis of VTE of with a safety tofacitinib trial In rheumatoid arthritis patients, an interim colleagues report real-world data first came to light in 2019 during analysiscreased infectionof a safety rates clinical and trialhigher of twice-dailylipid levels. registries. In this study, Deepak and prompted the FDA to issue a safety doses of 10 mg tofacitinib showed increased in rheumatoid arthritis. The data rates of pulmonary embolism and all-cause from a multicenter cohort. mortality, compared to treatment with a dose mostThe common study reported being infections low rate of and communication. In this study two adverse events (15.7%) with the patients developed VTE. Both were - use did not appear to increase risk edmales for ona cohort the 10-mg of this twice-daily size and high- dose. of 5 mg or a tumor necrosis factor antagonist. skin rashes. Interestingly, steroid Dr. Kaur lightsThis number the need is fora higher careful than patient expect ClinicalThat finding Gastroenterology led to a boxed and label Hepatology warning against(doi: thrombosis. The current study, published in of infections. Serious adverse events commonoccurred infectionin 5.8% and was included reactivation two of herpes selection, risk-benefit discussion, 10.1016/j.cgh.2020.06.050), included patients cases of venous thromboembolism (VTE). Most closeIn summary, monitoring most for adversesigns of effectsVTE, and related early counseledfrom six centers about the in thepotential United risk States. for herpes zoster higher 10-mg twice-daily dosing and, with the todose tofacitinib tapering can when be feasible.mitigated with careful The findings suggest that patients should be exceptionzoster virus of (HZV).one patient, All cases in HZV-unvaccinated occurred at the patient selection, pretreatment zoster vaccina-

(HZ) reactivation, especially older patients taking have been previously reported from pooled corticosteroids. The authors also recommended individuals. These rates are similar to what Manreettion, and Kaur, timely MD, dose medical taper. director of Inflam- vaccination with an inactivated HZ vaccine. matory Bowel Disease Center at Baylor College of The researchers followed 260 patients over a safety data of phase 2 and 3 clinical trials of Medicine, Houston. She has no conflicts of interest. previouslymedian of 6received months treatment (median age, with 38 a years;biologic, 58.1% most tofacitinib. Given these data, in my practice, I male; 71.9% non-Hispanic). Overall, 88.5% had encourage all patients to receive the first dose

Continued from previous page Despite those efforts, treatment - success is lower than with many oth- workof three meta-analysis or more regimens. that included 8.94), sequential therapy versus 76.4%). Levo-therapy performed The researchers conducted a net triple therapy (OR, 1.79; 95% CI, best in Western countries (88.5%; - is the potassium-competing acid - 1.26-2.53), nonbismuth quadruple 95% CI, 86.5-90.5%) and West Asia blockerer infectious vonoprazan, diseases. which A newcomer increases lowing68 randomized, regimens controlled were included trials in quadrupletherapy versus therapy triple versus therapy triple (OR, (88.4%; 95% CI, 84.6-91.1%). R-hy thetotaling analysis: 22,975 Concomitant patients. The quadru- fol 2.08; 95% CI, 1.45-2.98), bismuth bridA surface therapy under performed the cumulative best in East therapies and has, thereby, generated ple bismuth treatment (bismuth Asia (93.6%; 95% CI, 90.4-96.8%). renewedefficacy of interest amoxicillin in all combination combination therapy (OR, 1.47; 95% CI, 1.02- - therapies, according to the study au- quadruple nonbismuth treatment 2.11), and Levo-therapy versus ventionranking compared(SUCRA) value, to an whichideal inter- - (nonbismuthquadruple therapy), quadruple concomitant thera- tripleIn the therapy overall (OR, data, 1.79; mean 95% cure CI, represents the efficacy of the inter able in some Asian countries, but not 1.26-2.53). thors. Vonoprazan is currently avail vention, was 92.4% for Vono-triple Current guidelines for H. pylori py), high-dose amoxicillin double rates greater than 90% were seen therapy. The second highest SUCRA treatmentthe United reliedStates onor Europe.randomized treatment (Amox-dual therapy), only in Vono-triple therapy (91.4%; value was for 68.8% for nonbismuth controlled trials and relevant pair- levofloxacin-containing treatment- 95% CI, 88.5-93.5%) and R-hybrid quadrupleA key limitation therapy. to The the SUCRA study isvalue that wise meta-analyses, but no previous quential(Levo-therapy), quadruple reverse treatment hybrid (se- therapy (93.6%; 95% CI, 90.4- ofVono-triple standard therapytriple therapy was tested was 4.7%.only pairwise analysis has included all therapy (R-hybrid therapy), se 96.8%). Cure rates were lower for- currently available medications, the Nonbismuth quadruple therapy - vonoprazan-containingquential therapy), standard therapy triple (84.3%; 95% CI, 82.7-85.8%), Le in Japan, and requires additional treatment (triple therapy), and vo-therapy (83.8%; 95% CI, 82.1- study in other geographic regions. authors noted. Network meta-anal - 85.4%), Sequential therapy (83.7%; The study received support from directyses can evidence help fill from this aevidence collection gap: of were(Vono-triple found with therapy). Vono-triple thera- 95% CI, 82.7-84.7%), bismuth receivedthe Department research of funding Veteran from Affairs. var- randomizedThey incorporate controlled both directtrials toand esti- in pyStatistically versus triple significant therapy (odds results ratio, quadruple therapy (81.3%; 95% CI, The authors have consulted for and mate the comparative effectiveness 79.5-83.1%), Amox-dual therapy [email protected] (80.2%; 75.3%-84.4%), and triple ious pharmaceutical companies. MDedge.com/gihepnews / August 3.80;2021 95% confidence interval, 1.62- therapy (75.7%; 95% CI, 74.9- 23 †FROM THE AGA JOURNALS Who’s at risk for enterocolitis in Hirschsprung’s?

BY JIM KLING Mouse models have shown con- MDedge News nections between the immune and irschsprung’s disease is a he- cholinergic signals can prevent nervous system, but it has been Hreditary childhood disorder in n a small study of Hirschsprung’s challenging to study the effects which the enteric nervous system colon by modulating the immune disease (HSCR) patients, those develops abnormally excessive inflammationresponse to commensal in the I - humans. There are more than 30 in the distal bowel. microbes, which thus sal acetylcholinesterase-positive separateof specific neurotransmitters neurotransmitters in in the As a consequence, presents an example of (AChE+)with a low-fiberinnervation colonic phenotype muco enteric nervous system, making it peristalsis fails in the neuroimmune crosstalk. were more likely to suffer from aganglionic segment, Remarkably, the current postoperative enterocolitis, which functions. Because there are com- causing obstruction and study demonstrated that can be life-threatening. parativelydifficult to fewtease enteric apart nervousindividual sys- prestenotic megacolon. high levels of mucosal The study lends insight into cross- tem neurotransmitters in patients Standard of care is the acetyl choline positive talk between the human enteric with HSCR and the aganglionic surgical removal of the nervous and immune systems. It colon in these patients contains affected part of the co- correlated with lower suggests a role for acetylcholine-se- - lon and the connection Dr. Kaestner risknerve for fibers postoperative in the colon ronal cholinergic function can be of healthy ganglionic enterocolitis. Intriguing- aganglionic sections of colon in pa- examinedenlarged AChE+ particularly nerve well”fibers, among “neu tissue to the anus. Unfortunately, - tientscreting with (cholinergic) HSCR, which nerve is afibers congen- in these patients. a large fraction of Hirschsprung’s ber status in the colonic mucosa at ital disorder marked by the absence The researchers of the current patients suffer from enterocolitis, ly,time determination of surgery could of cholinergic thus become fi of enteric neuronal cells in the distal study analyzed tissue from 44 pe- diarrhea, and abdominal disten- a new prognostic marker for the part of the gut. diatric HSCR patients who under- tion either before or after surgery, risk of postoperative enterocolitis There are also potential clinical went pull-through surgery, along which can progress to life-threat- in Hirschsprung’s disease patients. implications. “These observations with 6 non-HSCR controls who had ening sepsis and organ failure. Further research is needed to suggest that HSCR patients with surgery for various other reasons. In a prospective, multicenter determine the reason for different Tissue samples were semiquantita- study, Keck and colleagues an- higher risk of developing postoper- tively categorized according to the alyzed colonic tissue recovered aganglionic colon and to validate low-fiber phenotype might have a extent of colonic mucosal AChE+ in- in the operating room to inves- levels of cholinergic fibers in the phenotype could serve as a predictive tigate the relationship between cohort. markerative enterocolitis for development and that of theprophy- fiber tissue lacked intrinsic nerve cell mucosal cholinergic innervation these findings in a separate patient lactic therapy,” wrote Simone Keck, bodiesnervation: and Low-fiber mucosal ACHe+ rectosigmoid innerva- and enterocolitis in pediatric Klaus H. Kaestner, PhD, MS, is di- PhD, of the University of Basel (Swit- Hirschsprung’s patients in un- rector of the Next Generation Se- zerland) and colleagues in a study nerve cell bodies but had mucosal precedented detail. This line of quencing Center at the University of published in Cellular and Molecular AChE+tion, while innervation. high-fiber The tissue researchers lacked investigation was motivated by Pennsylvania, Philadelphia. He has Gastroenterology and Hepatology also determined tissue cytokine prior observations showing that no conflicts of interest. (2021 Mar 16;12[2]:507-45). - HSCR is a multigenetic congenital - condition that includes a lack of orescenceprofile and microscopy immune cell to frequen determine Out of 42 patients, 9 developed postsurgical management of HSCR enteric ganglia cells (aganglionosis) proximitycies, and used of macrophages confocal immunoflu to nerve enterocolitis within 1 year of sur- by allowing clinicians to employ in the distal part of the colon, lead- preventive measures against en- ing to intestinal obstruction and determine microbial populations. - terocolitis. Th17 cells are known to prestenotic megacolon. Treatment fibersThey and found 16S-rDNA that aganglionic sequencing to ferencegery; 7 hadwas a not low-fiber statistically phenotype, sig- migrate to nearby mesenteric lymph consists of pull-through surgery while 2 were high fiber. This dif nodes, where they may promote en- to remove the aganglionic portion performed a retrospective analysis terocolitis, and this site is usually not of the bowel, but 20%-50% of theselow-fiber cytokines samples were had lower higher in levels both ofnificant, 29 HSCR but patients the researchers to validate then the removed during HSCR surgery. Fiber patients develop life-threatening ganglionicof inflammatory sections cytokines. of the colon Levels and of - phenotype could prompt a surgeon HSCR-associated enterocolitis be- terocolitis after surgery, with 12 of to also remove mesenteric lymph fore or after surgery. Although the - thefindings. cases Ofoccurring these, 14 among developed children en nodes to reduce enterocolitis risk. mechanism of the complication is plesin high-fiber also had sampleselevated with Th17 mucosal T cells, The study was funded by the Uni- uncertain, immune cells, intestinal AChE+ nerve fibers. Low-fiber sam- 2 cases occurred among those with versity of Basel. The authors have barrier function, and the microbi- onic, and ganglionic distal colon with the low-fiber phenotype, and ome may play a role. samples.compared with high-fiber, agangli [email protected] the high-fiber phenotype. no relevant financial disclosures. The findings could help guide Continued from previous page (median hemoglobin level, 13.6 g/dL; IQR, 12.57- facitinib in whom increasing age is a risk factor Risk factors for VTE were seen in 31.2% of the 14.0). At 52 weeks, the mean increase in hemo- for [adverse events] and consistent with recent cohort, and two cases of VTE occurred during globin was 5% (IQR, 0%-11.1%). The increase reports of a dose-dependent risk of HZ reactivation follow-up (1.32 per 100 person-years; 95% CI, was greater in females (7.7%; IQR, 4.2%-11.7%) and VTE events in patients with a risk factor for 0.33-5.28), both in patients with extensive UC. than in males (2.1%; IQR, –0.5% to 11.3%). VTE on the 10-mg twice-daily dosing,” the authors There was no increased risk of complications Limitations of the study include its retrospec- concluded. following abdominal surgery. At baseline, 38.4% tive nature and that the data-collection tools The study was funded by the American Col- could have missed some adverse events because lege of Gastroenterology, the Crohn’s and Colitis to 48.3% following 8 weeks of treatment. they were not adequately captured in the treating Foundation, the Givin’ it all for Guts Foundation, hadOverall, an abnormal 45% of lipidpatients profile, were and anemic this increasedat base- clinician’s notes. However, the data trend similarly - to a prospective study (Clin Gastroenterol Hepa- Bowel Disease Research Innovation and Educa- ment by week 26 (median hemoglobin level, 13.0 tol. 2020 Jan;18[1]:123-32.e3). and the Lawrence C. Pakula, MD, Inflammatory line.g/dL; Females interquartile experienced range, 12.5-13.8),a significant while improve a sim- “In summary, we report safety signals on a real- various pharmaceutical companies. ilar improvement occurred by week 52 in males world cohort of patients with UC initiated on to- tion Fund. The authors have [email protected] ties with

24 August 2021 / GI & Hepatology News

22_to_27_GIHEP21_08.indd 24 7/21/2021 3:46:24 PM NEWS FROM THE AGA Get to know 2021 award winners David Y. Graham, MD guished professor of medicine at the istry at University College London about a bit.” She is a proud member Dr. Graham is this year’s recipient University of California, San Diego, where she also stayed to complete of the band GI Distress as one of the of the AGA William Beaumont Prize and is serving as a rotating appoint- her PhD studies. After that, Dr. Bar- “Fabulous Fasebettes.” in Gastroenterology. A remarkable ment as director of the Division of rett moved to the United States to Read more about Dr. Barrett’s con- clinician, scientist, and mentor to the Graduate Education of the National continue her training at the National tributions to the GI community in next generation Science Foundation. Institutes of Health and continued a commentary in Gastroenterology of GI, Dr. Graham Born in London, Dr. Barrett was the studying the functional heterogeneity (2021 Jul;161[1]:336-8), written by currently serves of mast cells. She believes in having Mark Donowitz, MD, and Stephen as professor of She earned a BSc in Medicinal Chem- fun, living by the phrase “put yourself Keely, MD. medicine-gas- first of her family to attend college. troenterology at Baylor College of Medicine in Houston. Dr. Graham

Dr. Graham was born in Gastro_Advances_Inaugural-3.pdf 1 4/20/21 9:35 AM Ancon, in the Panama Canal Zone, where his father Submit to our newest journal Gastro Hep www.ghadvances.org

January 2022 was working as an engineer. The Advances Volume 1 / Number 1 family eventually settled in Lake Jack- Gastro Hep Advances son, a small gulf coast town outside of Houston. There he developed a Coming Soon! GHA is your home for high quality, open access research love for outdoor activities including Submissions Open July 1, 2021 on a broad range of topics in gastroenterology and hepatology. We are now looking for clinical, basic and He received a bachelor’s degree from translational research to include in this online-only thehunting, Notre fishing, Dame and returnedriding horses. home publication premiering January 2022. to Houston to receive his medical de- gree with honors from Baylor College WHY CHOOSE GHA of Medicine. Dr. Graham’s training Broaden the reach of your research was interrupted by the Vietnam War, Meet your funder mandate around open access during which he was drafted into the Get published in an AGA journal

In addition to his clinical and U.S.research Army missions, as a flight Dr. surgeon. Graham has mentored numerous individuals Learn more and submit your research at agajournals.org/ghadvances. during his years as a clinician scien- PUB21-004 tist, many of whom have gone on to have successful careers in academic medicine. He has been an active AGA member for more than 4 decades, receiving several honors including the prestigious AGA Mentor Award in 2015 and the Janssen Award for Spe- cial Achievement in Gastroenterology. Read more about Dr. Graham’s life and contribution to the GI commu- nity in a commentary in Gastroen- terology (2021 Jul;161[1]:333-5) Access #AGAPG written by Fasiha Kanwal, MD, and Hashem B. El-Serag, MD, MPH. content year round Kim E. Barrett, PhD, AGAF Dr. Barrett is the 2021 recipient of Did you miss the live 2021 AGA the AGA Distin- Postgraduate Course? Now you can guished Achieve- access the entire course on demand! ment Award in Basic Science for Discover new tools and learn about the her outstanding latest GI research for treating patients contributions to with digestive diseases. Plus, you can understanding earn up to 22 CME or MOC when you mechanisms and regulation of in- complete the course by Dec. 31, 2022. testinal epitheli- Dr. Barrett al transport and Learn more and purchase at pgcourse.gastro.org. EDU21-020 barrier function. She currently serves as distin-

MDedge.com/gihepnews / August 2021 25

22_to_27_GIHEP21_08.indd 25 7/21/2021 3:59:23 PM †LIVER DISEASE Novel liver dialysis device may safely curb ACLF

BY NEIL OSTERWEIL rhosis, at least one acute decompensation event, terial infections, bleeding, and progressive liver MDedge News and progression to ACLF grades 1, 2, or 3a. failure. Patients with an international normalized n investigational liver dialysis device (DI- ratio above 3 were excluded, as were those with more than three organ failures, uncon- There were eight instances of filters clotting Agreater survival of patients with acute- trolled infections, primary respiratory organ whereout of 64tubing filters could used not in total,be disconnected and four episodes from an on-chronicALIVE) liver was failure associated (ACLF), with compared significantly with failure, and hemodynamic instability refracto- of device deficiency, including two instances the standard of care in a multicenter random- ry to volume resuscitation and low-dose vaso- requiring use of new DIALIVE kits; one use of an ized study. pressors. Oxiris filter during setup of the DIALIVE circuit, Among 30 evaluable patients with ACLF from A total of 32 patients, of whom 30 were eval- of the DIALIVE circuit. alcoholic cirrhosis randomized to treatment with uable, were randomized to receive liver dialysis incorrect dialysis fluid; and one incorrect setup the DIALIVE system or standard of care, two- Significant improvements in many scores thirds of patients assigned to DIALIVE had both survived and experienced resolution of ACLF by in three to five DIALIVE sessions lasting 8-12 improvements over baseline at day 10 in both 28 days, compared with one-third of patients “It’s very early, but we’re really liverIn the scores DIALIVE (P < group, .05) and there brain were scores significant (P < .001). assigned to standard of care, reported Banwari desperate in finding something to In contrast, in the standard-of-care group there Agarwal, MBBS, MD, from the Royal Free Hospi- were no improvements in individual organ tal in London at the meeting sponsored by the bridge to transplantation.” European Association for the Study of the Liver. worse (P < .01). scores, and respiration scores were significantly Different from MARS hours each (15 evaluable patients) or to stan- improvements in CLIF-C organ failure scores, The DIALIVE system differs from the Molecular dard of care at participating institutions (15 comparedDIALIVE with was alsostandard associated of care with at day significant 5 and Adsorbent Recirculating System (MARS) liver patients). day 10 (P = .021 and .001, respectively); CLIF-C– dialysis system in that DIALIVE removes and The investigators looked at safety of the de- ACLF scores at days 5 and 10 (P = .045 and - vice (the primary endpoint) in all patients who .023); and Model for End-Stage Liver Disease received at least one DIALIVE treatment (safety scores at day 5 (P = .028). hereplaces explained. albumin, including proinflammatory al In the DIALIVE group, ­40% of patients had bumin, rather than filtering and recirculating it, of patients who received at least three DIALIVE ACLF resolution by day 5, and 66.7% had res- wasn’t quite the case with MARS,” he said in the treatments.population), and a modified safety population olution by day 10. In the standard-of-care arm, question-and-answer“It addresses systemic portion inflammation, of his presentation which The median patient age in each arm was 49 15% had resolution on day 5, and 33.3% had in a general session. In patients with ACLF, the years, and all patients had alcoholic cirrhosis, resolution on day 10. DIALIVE was also associ- risk of 28-day mortality increases substantially with alcoholic hepatitis accounting for at least as the grade of ACLF increases. one decompensation event. In addition, about resolution, compared with standard of care (10 “ACLF, however, is potentially reversible, and 25% of patients in each arm had decompensa- daysated withvs. not a significantlyreached; P = faster .0307). median At 28 days,time to10 the initial grade at presentation undergoes tion with infections and/or sepsis as precipitat- of 15 evaluable patients were alive and had reso- changes over time during the natural course of ing factors. lution of ACLF with DIALIVE versus 5 of 15 with the illness, with some patients deteriorating, standard of care (P = .0281). some improving, and some even achieving com- Safety Dr. Agarwal said that the data justify the im- Serious adverse events on days 1-10 occurred plementation of late-phase clinical trials of the - in 11 of 17 patients in the DIALIVE arm, and liver dialysis device. pletetermines ACLF their resolution. future outcome The final trajectory. grade is reached I there- in 8 in the standard-of-care arm. In the DIAL- byfore days propose 3-7, and that it ACLF is this resolution final grade in whichitself is de an IVE arm, there were seven treatment-related ‘Hopeful’ findings important therapeutic target,” he said. serious device events, three unexpected seri- “It’s very early, but we’re really desperate in ous device events (anemia, septic shock, and Study details hypotension), and one patient discontinued commented Tobias Boettler, MD, from the Uni- Dr. Agarwal and coinvestigators from eight cen- dialysis after having unsafe levels of thrombo- versityfinding ofsomething Freiburg to(Germany), bridge to transplantation,”who was not in- ters in six European countries enrolled patients cytopenia. volved in the study. with a history indicative of alcohol-related cir- Four patients in the DIALIVE arm died on “I think this is very hopeful,” said Dr. Boettler, - potension, coagulopathy, and multiorgan failure, andstudy. this The prompted first two a died change on dayin the 1 one protocol from hy whoIn themoderated question the and briefing answer where following Dr. Agarwal the mandating that DIALIVE be conducted only in talksummarized in a general the session,study findings. moderator Philip N. an ICU setting with more invasive monitoring Newsome, MD, from University Hospitals Bir- and more frequent lab analysis of clotting and mingham (England) asked whether patients who other biochemical parameters. Of the two other were not treated should have been included in patients in the DIALIVE arm who died on study, the analysis. one died from non-MI cardiac arrest on day 8, Dr. Agarwal replied that “the whole idea be- and one patient with ACLF grade 3 and a Euro- hind this study was to understand what this pean Foundation for the study of chronic liver device does to these patients, and how these failure (CLIF)–ACLF score of 68 died from multi- patients react to this device, so really not looking organ failure. “I must emphasize that even this very sick The study was supported by the European mages I patient tolerated the device very, very well,” Dr. Union’sat the efficacy.” Horizon 2020 initiative. Dr. Agarwal re- etty

G Agarwal said. ceived a study grant from the initiative, but had / In the standard-of-care arm, two patients died no other relevant disclosures. Dr. Boettler and Dr. from progressive liver failure on days 17 and 27, Newsome had no disclosures relevant to the study.

wiratgasem respectively, and one died on day 17 from bac- [email protected]

26 August 2021 / GI & Hepatology News †LIVER DISEASE Rapid HCV tests could expand accessibility

BY NEIL OSTERWEIL from those who have the disease problem of the high cost of treat- HCV prevalence of 1.5%. MDedge News and aren’t diagnosed, to those who ment, but this would at least make The model considers costs from a are tested and only partially diag- it a little more convenient,” he said. health care payer’s perspective, and proposed rapid diagnostic nosed because they don’t have a He noted that the success of the the investigations performed deter- test for hepatitis C viral in- strategy would be dependent on the ministic and probabilistic sensitivity Afections that combines an get into care, get treated, and get sensitivity of the rapid core-antigen analyses to evaluate how the cost-ef- inexpensive but lower-sensitivity cured,”confirmed she infection, said in an to interview. those that test, it’s cost relative to HCV RNA fectiveness of testing pathways core-antigen test with lab RNA con- “It’s all about closing the gaps in testing, and whether the availability might change when various factors the care cascade in order to achieve of the rapid test would translate were plugged into the model. expand testing and same-day initi- elimination of the virus, which is into an improvement in follow-up. As noted before, the investigators ationfirmation of antiviral of negative therapy tests in could places what we’re all trying to do,” she said. Neither Dr. Miller nor Dr. Hoerger determined that the core-antigen where resources are limited, inves- She pointed that there are certain were involved in the study. rapid test algorithm would improve tigators said. at-risk populations in the United diagnosis rates in Georgia from Applying the proposed method States, such as injectable-drug us- Evaluating the approach 78.8% to 95.4% and in Malaysia to the Republic of Georgia, with a To determine whether a lower-cost from 57.9% to 91.2%. The use of hepatitis C virus (HCV) prevalence from such a system. rapid test could be cost effective, the rapid test would also increase of 5.4% as reported by the World ers,“These who mightfolks often be able have to less benefit access the researchers created a micro- quality-adjusted life-years in Geor- Health Organization, would result to traditional care, so bringing rapid simulation model of the natural gia by 207 per 10,000 and in Malay- in a 95.4% diagnosis rate, com- testing and care to where those folks history of HCV to compare potential sia by 146 per 10,000. pared with 78.8% for lab-based are is really important, so if we can outcomes from either core-antigen Cost savings, primarily from RNA testing, which is the standard deploy mobile units to areas where rapid diagnostic testing with a base averting the costs of care for pa- of care. Applied to Malaysia, the there is high prevalence and do it case sensitivity for HCV viremia of tients with HCV, begin within the proposed method would boost di- - agnosis rates from 57.0% to 91.2%, entire process,” she said. mation for negative results or the years, the lifetime horizon cost sav- reported Madeline Adee, MPH, from at Thomasthe point J. ofHoerger, care, it PhD,simplifies a senior the current80% with standard lab-based of care RNA with confir lab- ingsfirst inyear Georgia of the wouldmodel. be Over $232,000 50 Massachusetts General Hospital’s - per 10,000 people, and the corre- Institute for Technology Assess- The model incorporated META- sponding savings in Malaysia would ment in Boston and colleagues. groupfellow RTIin health International economics in Researchand fi VIRbased stage RNA F0-F4, confirmation decompensated only. be $504,000 per 10,000 people. “We found that a novel core-an- Trianglenancing atPark, the N.C.,nonprofit said in research an in- cirrhosis, hepatocellular carcinoma, Even when allowing for varia- tigen rapid diagnostic test for HCV terview that the proposed model and liver-related death. The inves- tions in parameters, the core-anti- could improve the diagnosis rate and could eliminate the step in testing tigators determined the baseline gen rapid diagnostic test approach result in cost savings. Although not in which patients are required to characteristics of HCV patients in remained the preferred model, the yet developed, such a test could be a each country based on different investigators reported. game changer and have a substantial “People don’t always come back distributions of sex, HCV genotype, The study was supported by the impact on the feasibility and cost of forreturn further for confirmation. testing, so if you can do global health agency Unitaid. The HCV elimination, especially in low- it immediately and have the results They simulated outcomes for researchers, Dr. Miller, and Dr. Ho- and middle-income countries,” they of a screening test, you might be 10,000and METAVIR adults fibrosis in the Republic stage. of - reported at EASD 2021, the meeting able to get people to come back Georgia, with an HCV prevalence est relevant to the study. sponsored by the European Associa- more quickly. You still have the of 5.4%, and Malaysia, with an erger reported no [email protected] of inter tion for the Study of the Liver. Although rapid tests for HCV can improve diagnosis and treatment rates, currently available molecular tests are expensive and require clin- ical laboratory infrastructure, which Principles can put such tests out of the reach for clinicians in low- or middle-in- come countries. Rapid immunoas- of GI for the says based on HCV core antigens are cheaper, but their sensitivity ranges from 70% to 90%; in contrast, the NP and PA third-generation HCV enzyme immu- noassay has about a 98% sensitivity. Aug. 14-15, 2021 | Virtual

Could it work? Acquire stronger diagnostic and therapeutic skills The proposed testing method to effectively treat and manage GI disorders through would be likely to improve diag- tailored instruction from our faculty of expert nosis, but whether that would physicians and advanced practice providers. translate into increased treatment Course directors: is uncertain, commented Lesley • John Clarke, MD, AGAF, Stanford Health Care Miller, MD, who specializes in HCV • Kimberly Kearns, MS, ANP-BC, DuPage Medical Group screening and treatment in under- • Kian Keyashian, MD, Stanford Health Care served populations at Emory Uni- • Jody Weckwerth, PA-C, Mayo Clinic, Rochester, MN versity, Atlanta. “When we’re talking about Learn more at nppa.gastro.org. hepatitis C, it’s all about the care cascade, the drop-off at each step

MDedge.com/gihepnews / August 2021 27

22_to_27_GIHEP21_08.indd 27 7/21/2021 3:46:36 PM †LIVER DISEASE Patients with HIV/HCV see better transplant outcomes

BY ANDREW D. BOWSER away from our study,” Dr. Wang said. Action, a prospective, multicenter, Accordingly, Dr. Wang and col- MDedge News Moreover, relatively few centers clinical trial evaluating the safety leagues analyzed Organ Procure- are performing liver transplants and survival outcomes of HIV-pos- ment and Transplantation Network FROM DDW 2021 for patients who are HIV/HCV itive deceased-donor liver trans- (OPTN) data on adult patients who hile liver transplant out- plants in HIV-positive recipients. underwent liver transplants be- comes were historically geographic variation in where the tween 2008 and 2019 to see if the Wpoor in people coinfect- procedurescoinfected, andare theredone, isshe significant said in Impact of the HOPE Act, DAAs introduction of DAAs had leveled ed with HIV and hepatitis C virus her presentation. Liver transplantation for HIV-posi- - tive patients has increased since the coinfection. cantly in the era of direct-acting Reassuring data that signing of the HIV Organ Policy Eq- theOverall, playing out field of for70,125 those liver with trans- HCV antiviral(HCV), they (DAA) have therapy, improved a recent signifi should prompt referral uity (HOPE) Act in 2013, according plant recipients over the 2008- analysis of U.S. organ transplant Taken together, these results should to Dr. Wang. 2019 period, 416 (0.6%) were HIV data showed. offer reassurance to transplant The HOPE Act expanded the donor infected, the data show. In 2014, 28 The availability of highly potent centers that patients coinfected pool to include HIV-positive deceased liver transplants (0.5%) were per- DAA therapy should change how with HIV/HCV are no longer at donors, which not only increased the formed in HIV-infected individuals, transplant specialists view patients increased risk for poor outcomes - which increased to 64 transplants coinfected with HIV/HCV who need after transplantation, said Christine ly helped HIV-positive individuals, (0.8%) in 2019, data show. Of those a liver transplant, according to re- M. Durand, MD, associate professor whodonor experience supply overall, a higher but ratespecifical of 64 HIV-positive liver transplant re- searcher Jennifer Wang, MD, chief of medicine at Johns Hopkins Uni- waiting-list mortality, according to a cipients in 2019, 23 (35.9%) were gastroenterology fellow at the Uni- versity, Baltimore. review on the topic coauthored by Dr. coinfected with HCV. Graft survival versity of Chicago, who presented “The additional call for action Durand (Curr Opin Organ Transplant. has greatly improved, from a 3-year the results of the analysis at the should be beyond the transplan- 2018 Apr;23[2]:271-8). survival of only 58% in patients annual Digestive Disease Week® tation community to ensure that However, some transplant cen- transplanted before the availability (DDW). Cumulative graft survival referrals for liver transplant are ters may be reluctant to do liver of DAAs to 82% in the DAA era, a rates since the introduction of DAAs where they should be,” Dr. Durand transplants in HIV-positive patients difference that was statistically sig- are comparable between transplant said in an interview. coinfected with HCV. That’s be- recipients with HIV/HCV coinfection “With a number of only 64 cause, in previous studies that were - and recipients who are both HIV and transplants a year, we’re not doing conducted before the DAA era, out- closuresnificant, relatedDr. Wang to thesaid. research. Dr. HCV negative, according to the study. enough, and there are more pa- comes after liver transplant in HIV/ Dr. Wang provided no financial dis- “Having hepatitis C no longer con- HCV-coinfected patients were infe- ships with AbbVie, GlaxoSmithKline, fers worse patient survival in the transplants,” added Dr. Durand, who rior to those in patients with HIV andDurand Gilead disclosed Sciences. financial relation DAA era, and this is the main take- istients principal that could investigator benefit offrom HOPE liver in but no HCV infection, Dr. Wang said. [email protected] Safety-net burden linked with poorer inpatient cirrhosis outcomes

BY HEIDI SPLETE The new analysis included 322,944 individual ties in in-hospital mortality among cirrhosis-re- MDedge News hospitalizations of patients with cirrhosis. In lated hospitalizations,” the researchers wrote. terms of safety-net burden, 107,446 hospital- Overall, the odds of in-hospital mortality were atients with cirrhosis treated at hospitals izations were at high-burden hospitals, 103,508 27% higher in Black patients as compared with P were at medium-burden hospitals, and 111,990 White patients. by their proportion of Medicaid or uninsured hospitalizations were at low-burden hospitals. patients,with the had highest a 5% higher safety-net mortality burden, rate defined than Overall, cirrhosis-related hospitalizations in observed in Hispanic patients as compared patients who were treated at hospitals with hospitals with the highest withHowever, White patientssignificantly (4.9% lower vs. 6.0%; mortality P < .001),was the lowest burden, according to a study of over burden were found to have but why this occurred was not entirely clear. 300,000 patients. “Hispanic patients may be more likely to have The study, which was published in the Jour- in-hospital mortality than the NASH [nonalcoholic steatohepatitis]–related nal of Clinical Gastroenterology (2020 Oct. doi: lowest-tertilesignificantly greater hospitals odds (odds of cirrhosis, which generally has a slower disease 10.1097/MCG.0000000000001452), analyzed ratio, 1.05; P = .044). They progression, compared with [hepatitis C virus] data from the National Inpatient Sample (NIS) also had a higher proportion or alcoholic cirrhosis. As such, it is likely that database focusing on a 4-year time span be- of male patients, minority NASH-cirrhosis Hispanic patients had less severe tween 2012 and 2016. The hospitals were cate- patients, Hispanic patients, disease at presentation,” the researchers wrote. and patients with Medicaid as having either a high, medium, or low number Dr. Wong or no insurance. factors including the inability to show causal- ofgorized uninsured by safety-net patients burden,or patients which with was Medicaid. defined The odds of hospitalization ityThe based study on findingsthe observational were limited study by designseveral in the highest-tertile hospitals were found to be and cross-sectional nature of the database, the impact of a hospital’s safety-net burden on researchers said. The NIS database records in- hospitalizationThis is the first-known outcomes studyin cirrhosis to evaluate patients, the and lowest tertiles for Blacks and Hispanics, dividual hospitalizations, not individual patient wrote authors Robert J. Wong, MD, MS, of Stan- comparedsignificantly with higher, Whites compared (OR, 1.26 with and the OR, middle 1.63, data which means that it may include repeat ford (Calif.) University and Grishma Hirode, MAS, respectively). Black patients (OR, 1.26; 95% hospitalizations from the same patient. In addi- of the University of Toronto. Previous studies P < .001) and His- tion, the study was limited by a lack of data on have shown that safety-net hospitals, especially panic patients (OR, 1.63; 95% CI, 1.50-1.78; P< outpatient cirrhosis outcomes and non–liver-re- those with a high safety-net burden, have poorer .001)confidence were moreinterval, likely 1.17-1.35; to be admitted for care at lated comorbidities. patient outcomes. These hospitals also serve a high-burden hospitals (26%-54%). The study received no outside funding. The re- patient population that is at high risk for chronic “Despite adjusting for safety-net burden, our liver disease and cirrhosis. study continued to demonstrate ethnic dispari- [email protected] searchers had no financial conflicts to disclose. 28 August 2021 / GI & Hepatology News

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MDedge.com/gihepnews / August 2021 29 †LIVER DISEASE Calories may outweigh nutrients in diets for fatty liver

BY LAIRD HARRISON The researchers asked women in the LCHF diet to eat an average of ntermittent calorie restriction 1,600 kcal/day and men to eat an offers only modest advantages average of 1,900 kcal/day. All the Iover a low-carbohydrate, high-fat participants used recipes based on (LCHF) diet for treating nonalco- holic fatty liver disease (NAFLD), vegetables, and dairy fat. Participants researchers say. avoidedmeat, fish, sugar, eggs, bread, low-carbohydrate pasta, rice, pies, The intermittent diet offers potatoes, and fruit. The calories in more benefit for liver stiffness the recipes were composed of 5%- and LDL cholesterol, and might be 10% carbohydrates, 50%-80% fat, easier to maintain, said Magnus and 15%-40% protein. Holmer, MD, head of the hepatolo- All the participants reported what gy unit at the Karolinska Institute they ate over the previous 3 days, in Stockholm. both at the start of the study and But the intermittent diet also has after 12 weeks. Participants in the

drawbacks and the differences be- Tock 5:2 and LCHF groups also received tween the two were slight, he said S follow-up calls to report their past hink

in an interview. /T 24 hours of eating at 2, 4, 8, and 12 “They were more or less iden- weeks, and also at week 6, when

tically effective in reducing liver gerenme they visited a dietitian. steatosis in NAFLD and also re- In addition, the researchers mea- ducing body weight,” he said. “And How do the two day, and avoid large portions. sured the participants’ linoleic acid from this, we can say that the diets compare? The researchers asked women in and alpha-linolenic acid intake to composition of macronutrients To see if one was more effective the 5:2 diet to eat up to 500 kcal/ verify that the participants’ diets such as fat or sugar seems to be than the other, the researchers day each of 2 days per week and were different among the groups. less important than how many recruited 74 people with NAFLD. up to 2,000 kcal/day each of the After 12 weeks, all three groups calories you eat.” They diagnosed the patients either other 5 days. They asked men in Dr. Holmer and colleagues pre- by radiologic assessment or a com- the group to eat up to 600 kcal/day but the LCHF and 5:2 groups lost bination of controlled attenuation each of 2 days per week and up to morelost a thansignificant the standard amount care of liver group. fat, sponsored by the European Associ- parameter (CAP) greater than 280 2,400 kcal/day the other 5 days. - ationsented for their the findingsStudy of atthe the Liver meeting and dB/m and obesity, or a CAP greater They provided all the 5:2 partic- cantly in the 5:2 and standard-care published them in JHEP Reports than 280 dB/m, elevated ALT, and ipants with recipes that followed groups,Liver stiffness but not decreased in the LCHF signifi group. (2021 Feb 17. doi: 10.1016/j.jhe- overweight. Sixteen of the patients the Nordic Nutrition Recommen- The differences in steatosis change pr.2021.100256). were being treated with statins. dations, an adaptation of the Med- between the standard-care and While previous studies have The researchers randomly as- iterranean diet that emphasizes LCHF groups was statistically signif- shown that dieting can effectively signed 25 people to an LCHF diet, foods traditional in Nordic coun- icant (P = .001), as it was between treat NAFLD, researchers have de- 25 to a 5:2 diet, and 24 to standard tries, particularly grains such as the standard-care and 5:2 groups bated whether popular LCHF diets care. The groups were similar in whole-grain rye, oats, and barley; (P = .029). The differences between might cause more harm than good. diet, age, body mass index, liver fruits such as apples, pears, ber- the LCHF and 5:2 groups were not At the same time, intermittent stiffness, and most other criteria at ries, and plums; root vegetables, calorie restriction diets have also baseline, although there were more cabbages, onions, peas, beans, steatosis, but they were statistically been gaining in popularity. Among women in the standard-care group. statistically significant for weight or the most popular is the 5:2 diet, At the start of the study, the par- products; and the use of rapeseed - in which participants eat normally ticipants in the standard-care group (canola)fish, boiled oil. potatoes, The calories and provideddairy cantlysignificant reduced for liver total stiffness. and LDL choles- for 5 days a week and restrict their consulted with a hepatologist who in the recipes were composed of terol,In addition, while the the standard-care 5:2 group signifi group advised them to avoid sweets and 45%-60% carbohydrates, 25% fat, did not. In the LCHF group, levels of days. saturated fats, eat three meals a and 10%-20% protein. Continued on following page calories significantly the other 2

Q1. Correct answer: C. Esophagogastric Q2. Correct answer: A. CT scan.

Rationale Rationalejunction outflow obstruction. Given the change in bowel habits, colonoscopy in indicated to Recent studies recognized the role of medications in inducing esophageal motor evaluating sphincter function. Endoanal ultrasound can identify disorders. Opiates have been shown to be analevaluate sphincter for inflammation. defects in the Anorectal internal manometryor external analis helpful sphincter. in Quick Quiz associated with esophagogastric junction Digital rectal exam is important in evaluating the anal area for - 1), and other hypercontractile esophageal answers abnormalities.outflow obstruction, achalasia (not type skin tags, fissures, or scar. Digital exam can evaluate for rest toing the anal evaluation sphincter of tone a functional and squeeze, disorder. pelvic floor descent, and Reference strength of the pelvic floor muscles. CT is unlikely to contribute Camilleri M et al. Clin Gastroenterol Hepatol. 2017 Reference Sep;15(9):1338-49. Bharucha AE et al. Gastroenterology. 2006 Apr;130(5):1510-8.

30 August 2021 / GI & Hepatology News

28_30_31_GIHEP21_08.indd 30 7/21/2021 3:48:52 PM Continued from previous page of Oxford (England), said that lon- activity as well as eating less. grants from the Stockholm County LDL cholesterol, HDL cholesterol, ger-term results will be important. Still, Dr. Harrison greeted the Council, the Dietary Science Foun- and total cholesterol all increased. For example, it will be interesting dation (Kostfonden), the Skandia The long-term implications of the to see if the diets had effects on bal- “This is an important study.” Research Foundation, and the Åke findingsIt’s useful enthusiastically, to compare two saying: popu- Wiberg Foundation. Dr. Holmer has Holmer said. He hopes to follow Another limitation of the study is lar diets head B:to 7.875" head, and it’s also - upcholesterol on these findings patients are after unclear, 18-24 Dr. thatlooning it is orrelatively inflammation. small in size, he T: 7.625" tionships. Dr. Harrison is a consul- months. But the initial cholesterol said. He pointed out that people with that either oneS: can7.125" work, he added. tantdisclosed to Madrigal no relevant Pharmaceuticals. financial rela - NAFLD should increase their physical encouragingThe study wasto get supported confirmation by [email protected]

historyfindings of are cardiovascular perhaps enough disease. to con stitute a red flag for anyone with a Diet adherence Only one person dropped out of the

LCHF group and four in the stan- dard-care5:2 group, group.compared More with people five in the LCHF group reported adverse events, such as gastrointestinal upset. “With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for break- fast, for lunch, and for dinner. They might eat bacon and eggs for break- fast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons. The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet

would not work well for people with B: 9.625" S: 8.875" T: 9.375" insulin-dependent diabetes because

levels on fasting days. He also rec- ommendedof the difficulty against of adjusting this diet insulinfor peo- ple with cirrhosis because they need to eat frequent meals.

LCHF and 5:2 diets can work But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said. “I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interest-

- ageed in that.” some sort of specific diet, then I can,Stephen based onHarrison, these findings, MD, a visiting encour professor of hepatology at Radcliffe Department of Medicine, University INDEX OF ADVERTISERS Biomerieux BioFire 13

Braintree Laboratories, Inc. Sutab 31-32

Bristol-Myers Squibb Company Zeposia 4-8

Takeda Pharmaceuticals U.S.A., Inc. Entyvio 16-19

MDedge.com/gihepnews / August 2021 31

28_30_31_GIHEP21_08.indd 31 7/21/2021 3:48:53 PM

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