Quick viewing(Text Mode)

A Guide to Diagnosing and Managing Ascites in Cirrhosis

A Guide to Diagnosing and Managing Ascites in Cirrhosis

Muhammad Salman Faisal, MD; Tavankit Singh, MD; Hina Amin, A guide to diagnosing and MD; Jamak Modaresi Esfeh, MD Department of Internal managing in Medicine (Dr. Faisal) and Department of , Combined serum and ascites fluid measurements and Nutrition (Drs. Singh, Amin, and point to the cause of ascites. For patients with modest Modaresi Esfeh), Cleveland Clinic, Ohio , a reduced weight-loss target with diuresis may be acceptable. [email protected]

The authors reported no potential conflict of interest relevant to this article. iver cirrhosis is implicated in 75% to 85% of ascites cases doi: 10.12788/jfp.0186 PRACTICE RECOMMENDATIONS in the Western world, with or accounting for fewer cases.1 Among patients who have ❯ Calculate the serum ascites L albumin gradient and decompensated cirrhosis with ascites, annual mortality is 2 measure the total ascites 20%. Another study showed a 3-year survival rate after onset 3 protein level to distinguish of ascites of only 56%. It is vital for primary care physicians cirrhotic ascites from that (PCPs) to be alert for ascites not only in patients who have risk caused by heart failure factors for chronic disease and cirrhosis—eg, a history of or other disorders. C alcohol use disorder, chronic viral infections ( B and ❯ Recommend sodium C), or metabolic syndrome—but also in patients with abnor- restriction of 4.9-6.9 g for mal and thrombocytopenia. In this review, patients with established we discuss the initial assessment of ascites and its long-term ascites secondary management, concentrating on the role of the PCP. to cirrhosis. C ❯ Avoid giving angiotensin- converting enzyme inhibitors, Pathophysiology: angiotensin receptor Vasodilation leads to a cascade blockers, and nonsteroidal Splanchnic vasodilation is the main underlying event trig- anti-inflammatory gering a pathologic cascade that leads to the development drugs in cirrhosis. C of ascites.4 Initially in the setting of liver

Strength of recommendation (SOR) and fibrosis causes the release of inflammato- A Good-quality patient-oriented ry cytokines such as nitric oxide and carbon monoxide. This, evidence in turn, causes the pathologic dilation of splanchnic circula- B Inconsistent or limited-quality patient-oriented evidence tion that decreases effective circulating volume. Activation  C Consensus, usual practice, of the sympathetic nervous system, vasopressin, and -­ opinion, disease-oriented angiotensin- system (RAAS) then causes the proxi- evidence, case series mal and distal tubules to increase renal absorption of sodium and water.5 The resulting volume overload further decreases the heart’s ability to maintain circulating volume, leading to increased activation of compensating symptoms. This vicious cycle eventually manifests as ascites.6 A complex interplay of cirrhosis-associated immune dys- function (CAID), gut dysbiosis, and increased translocation of microorganisms into ascitic fluid is also an important aspect

174 THE JOURNAL OF FAMILY PRACTICE | MAY 2021 | VOL 70, NO 4 FIGURE 1 Mechanisms of cirrhosis-associated immune dysfunction (CAID)7,8 Damage to hepatocytes, gut dysbiosis, and increased bacterial translocation expose the compromised host immune system to pathogen-associated molecular patterns and damage-associated molecular patterns. Translocated bacteria activate inflammatory cells in gut-associated lymphoid tissue and mesenteric lymph nodes. This causes parallel processes of widespread systemic inflammation, hemodynamic disturbances, and endothelial activation contributing to many complications of cirrhosis, including ascites. A decrease in the ability to act against pathogens, combined with poor clearance by the reticuloendothelial system, leads to increased susceptibility to infections, including spontaneous bacterial .

Gut dysbiosis Damage to and Cirrhosis hepatocytes bacterial translocation

Cirrhosis-associated DAMPs PAMPs immune dysfunction

Immune deficiency Systemic inflammation • Damaged reticuloendothelial system • Increased bacterial translocation activates inflammatory cells in GALT • Poor neutrophil and macrophage and MLNs, leading to: phagocytosis and function - elevated levels of inflammatory • Decreased B- and T-cell proliferation cytokines TNFα, IL6, IFNγ and function - endothelial activation and more • NK cells lose cytotoxic effects inflammatory receptors such as • Decreased production of ICAMs, VCAMs complements by liver • Decreased opsonization

• Endothelial dysfunction • Hemodynamic disturbances • Increased susceptibility to bacterial infections

Manifestations of decompensated cirrhosis, including ascites

DAMPs, damage-associated molecular patterns; GALT, gut-associated lymphoid tissue; ICAMs, intercellular adhesion molecules; MLNs, mesenteric lymph nodes; NK, natural killer; PAMPs, pathogen-associated molecular patterns; VCAMs, vascular cell adhesion molecules.

of the pathogenesis.7 CAID (FIGURE 1)7,8 is an to the effects of damage-associated molecu- immunodeficient state due to cirrhosis with lar patterns (DAMPs) from hepatocytes and reduced phagocytic activity by neutrophils ­pathogen-associated molecular patterns and macrophages, T- and B-cell hypopro- (PAMPs) from the gut microbiota on the im- liferation, and reduced cytotoxicity of natu- mune system, which leads to many of the ral killer cells. In parallel, there is increased manifestations of decompensated cirrhosis production of inflammatory cytokines due including ascites.8 CONTINUED

MDEDGE.COM/FAMILYMEDICINE VOL 70, NO 4 | MAY 2021 | THE JOURNAL OF FAMILY PRACTICE 175 TABLE Initial work-up for possible cirrhosis-associated ascites

History • Ask about abdominal fullness, recent weight gain, ankle edema. • Ask about risk factors for liver disease and ascites: ; features of metabolic syndrome; drug use; unsafe sexual practices; history of travel; history of cardiac, renal, or thyroid disease; or malignancy. Physical exam • Check for distended , flank dullness, positive , and fluid thrill. • Look for signs of : spider angiomas, , caput medusae, tremor/asterixis, palmar erythema, . Labs, imaging • Order blood tests: , comprehensive metabolic panel, prothrombin time/ international normalized ratio. • Consider ordering ultrasound to detect abdominal fluid, even if it’s not clinically apparent; it can also detect abnormal liver morphology and signs of portal hypertension (eg, ), or locate a site for . A Doppler exam can detect patency of hepatic vasculature. Paracentesis • Check cell count and differential, albumin, and total protein on all samples.

• Calculate SAAG in ascitic fluid (see FIGURE 2). • Consider obtaining cytology, adenosine deaminase, triglyceride, gram stain, and culture. SAAG, serum ascites albumin gradient.

Key in on these elements ascites, may include spider angiomas on the of the history and exam upper trunk (33% of cirrhosis patients),13 Each step of the basic work-up for ascites pro- gynecomastia (44% of cirrhosis patients),14 vides opportunities to refine or redirect the palmar erythema, jaundice, asterixis, and diagnostic inquiry (TABLE). abdominal wall collaterals including caput medusa.15 History We suggest a systematic and targeted Generally, patients with ascites present with approach to using various physical exam weight gain and symptoms of abdominal maneuvers described in the literature. If the distension, such as early satiety, , and patient has a full/distended abdomen, per- . Besides cirrhosis, rule out other cuss the flanks. If increased dullness at the causes of ascites, as treatment differs based flanks is detected, check for shifting dullness, on the cause.9 Also ask about histories of can- which indicates at least 1500 mL of fluid in the cer and cardiac, renal, or thyroid disease.10 abdomen.16 Keep in mind that a 10% chance Patients with ascites in the setting of of ascites exists even if shifting dullness is liver disease usually are asymptomatic in its absent.17 Maneuvers such as the early stages. Common complaints are vague and fluid thrill are less accurate than shift- , generalized weakness, mal- ing dullness, which has 83% sensitivity and aise, and fatigue.11 Ask patients about risk fac- 56% specificity in detecting ascites.17 Patients tors for liver disease such as obesity, diabetes, with cirrhosis also have a high likelihood of hypertension, alcohol use, unsafe sexual complications from ascites such as inguinal, practices, recent travel, and needle sharing umbilical, and other . or drug use. Due to a strong association be- tween obstructive sleep apnea and fatty liver disease, consider screening at-risk patients Diagnostic work-up for sleep apnea.12 includes blood tests and ultrasound ❚ Blood tests. The initial work-up for asci- Physical exam tes should include complete blood count, When there are risk factors for liver disease, complete metabolic panel, and prothrombin examine the patient for stigmata of cirrhosis time/international normalized ratio.18 and ascites. Signs of liver disease, aside from ❚ Abdominal ultrasound is recommend-

176 THE JOURNAL OF FAMILY PRACTICE | MAY 2021 | VOL 70, NO 4 ASCITES IN CIRRHOSIS

ed as the first-line imaging test.19 Aside from lated by subtracting the level of ascitic fluid detecting ascites, it can give an estimate of albumin from serum albumin level (SAAG = the volume of ascites and indicate whether it serum albumin – ascitic fluid albumin). is amenable to paracentesis. A vascular exam A SAAG ≥ 1.1 g/dL is consistent with por- added to the standard ultrasound can detect tal hypertension,28 with approximately 97% radiologic evidence of portal hypertension accuracy. such as splenomegaly, portosystemic col- After calculating SAAG, look at total laterals, splenorenal , patency of the protein levels in ascitic fluid. Total pro- paraumbilical vein, and portal vein diameter. tein concentration ≥ 2.5 g/dL with SAAG Patients with established cirrhosis also re- ≥ 1.1 g/dL has a 78.3% diagnostic accuracy quire abdominal ultrasound every 6 months in determining heart failure as the cause of to screen for hepatocellular .20 ascites, with a sensitivity of 53.3% and speci- ❚ Abdominal paracentesis is the corner- ficity of 86.7%.28 On the other hand, a value stone of ascites evaluation.21 It is indicated of total protein < 2.5 g/dL indicates cirrhosis, for every patient with new-onset ascites or , or acute hepatitis as the cause of for any patient with known ascites and clini- fluid build-up.29 Stepwise evaluation of SAAG cal deterioration. Ascitic fluid analysis can and total protein and how they can point to- be used to easily differentiate portal hyper- ward the most likely cause of ascites is pre- tension from other causes of ascites. It can sented in FIGURE 2.27-29 also be used to rule out bacterial peritonitis. Calculating The recommended sites for evaluation are in the serum the left lower quadrant, 3 cm cranially and Management ascites albumin 3 cm medially from the anterior superior Noninvasive measures gradient better iliac spine.22 A large cohort study showed ❚ Sodium restriction. The aim of treatment characterizes that abdominal ultrasound-guided para- for uncomplicated clinically apparent asci- ascitic fluid than centesis reduced bleeding complications by tes is sodium restriction and removal of fluid total protein- 68% following the procedure and is strongly from the body. Dietary salt restriction is com- based tests. recommended (if available).23 Generally, plicated, and care should be taken to prop- paracentesis is a relatively safe procedure erly educate patients. Salt restriction advised with a low risk of complications such as ab- in the literature has shifted from a strict mea- dominal wall hematoma (1%), hemoperito- sure of < 2 g/d30 to more moderate strategies neum (< 0.1%), bowel perforation (< 0.1%), (described below).18 and infection (< 0.1%).24 The 2 main reasons for this easing of re- Assess all ascitic fluid samples for color, striction are issues with patient compliance consistency, cell count and differential, al- and concerns about adverse effects with bumin, and total protein. These tests are aggressive salt-restricted diets. One study usually sufficient to provide evidence regard- assessing patient compliance with a salt- ing the cause of ascites. If there is suspicion restricted diet found that more than two- of infection, order a gram stain and culture thirds of the patients were noncompliant,31 (80% sensitivity for detecting an infection if and 65% of the patients incorrectly assumed obtained prior to initiation of antibiotics)25 they were following the plan, which sug- and , (useful to gests poor dietary education.31 Of the group differentiate primary from secondary bacteri- that was compliant, 20% actually decreased al peritonitis),26 and amylase tests. Other tests their caloric intake, which can be detri- such as cytology, acid-fast bacilli smear and mental in liver disease.31 Concerns have culture, and triglyceride level should only be been raised that aggressive salt restriction obtained if specific conditions are suspected along with use can lead to diuretic- based on high pretest probabilities. induced and renal failure.32 Calculating serum ascites albumin gra- Current European Association for the Study dient (SAAG) is recommended as it has been of the Liver (EASL) guidelines recommend shown to better characterize ascitic fluid than salt restriction to a more moderate degree total protein-based tests.27 SAAG is calcu- (80-120 mmol/d of sodium). This is equiva-

MDEDGE.COM/FAMILYMEDICINE VOL 70, NO 4 | MAY 2021 | THE JOURNAL OF FAMILY PRACTICE 177 FIGURE 2 Using SAAG and total protein level to determine the cause of ascites27-29

No Is SAAG ≥ 1.1 g/dL? If SAAG is < 1.1 g/dL, focus on the following possible diagnoses:

Yes - Peritoneal carcinomatosis - Pancreatic ascites - Biliary ascites Measure total protein in the - Bowel obstruction/perforation ascitic fluid. No - Is it < 2.5 g/dL? - Lymphatic leak - Serositis from inflammatory disease

Yes

If total ascitic protein is ≥ 2.5 g/dL, focus on Consider these diagnoses: the following possible diagnoses: - Cirrhosis - Constrictive pericarditis, congestive heart failure - Liver failure - Early Budd Chiari syndrome - Acute hepatitis - Sinusoidal obstruction - Inferior vena cava obstruction

SAAG, serum ascites albumin gradient.

lent to 4.9-6.9 g of salt (1 tablespoon is rough- benefit with no increase in adverse effects.34 ly equivalent to 6 g or 104 mmol of sodium).18 Since the patient population in this study was ❚ . Initiation and dosage of di- more in line with what a PCP might encoun- uretic therapy is a matter of some controver- ter, we recommend following this guideline sy. Historically, simultaneous administration­ initially and keeping a close watch on serum of a and mineralocorticoid electrolytes. receptor blocker were recommended: Usual maximum doses are spironolac- 40 mg and 100 mg spironolac- tone 400 mg/d and furosemide 160 mg/d.21,35 tone, keeping the ratio constant with any Adequate weight loss for patients with dif- dosage increases. This was based on a ran- fuse edema is at least 1 kg/d, per EASL guide- domized controlled trial (RCT) showing lines.36,37 However, this might not be practical that the combined diuretic therapy effec- in outpatient settings, and a more conserva- tively mobilized ascites in a shorter period tive target of 0.5 kg/d may be used for patients of time and with less frequent adverse effects without significant edema.37 (eg, hyperkalemia) compared with initial It is vital to get accurate daily weights and monotherapy.33 avoid excessive diuretic use, as it has been as- On the other hand, another study with sociated with intravascular volume depletion more stable patients and relatively normal re- and acute kidney injury (25%), hyponatre- nal function showed that starting with a min- mia (28%),38,39 and hepatic eralocorticoid receptor blocker alone with (30%).40 Therefore, patients with acute kidney sequential dose increments had equivalent injury, hyponatremia, acute variceal hemor-

178 THE JOURNAL OF FAMILY PRACTICE | MAY 2021 | VOL 70, NO 4 ASCITES IN CIRRHOSIS

rhage, or infection should also have their di- cialist care is required to improve survival and uretics held until their creatinine returns to quality of life for these patients. They should baseline. be referred to a hepatologist for consideration of TIPS placement or .18 Invasive measures Long-term use of albumin was tested in ❚ Large-volume paracentesis. Patients with 2 trials for management of decompensated extensive and tense ascites should be treated cirrhosis with ascites, yielding conflicting initially with large-volume paracentesis, as results. The ANSWER trial from Italy showed this has been shown to predictably remove benefit with this treatment for prolonged sur- fluid more effectively than diuretics.38 This vival.46 The other trial, from Spain, showed should be accompanied by albumin admin- no benefit from albumin and midodrine istration, 8 g for every liter of ascitic fluid administration for survival or for improving removed if the total amount exceeds 5 L.41 complications of cirrhosis.47 The contradic- Following large-volume paracentesis, man- tory results are likely due to heterogeneous age patients with the standard salt restriction populations in the 2 trials and differences in and diuretic regimen.38 Serial large-volume dose and duration of albumin administra- paracentesis is a temporary measure re- tion. Hence, no clear recommendations can served for a select group of patients who are be made based on the available data; further intolerant to diuretics and are not candidates research is needed. for a shunt. Diuresis with ❚ Transjugular intrahepatic portosys- Getting a handle on mineralocorticoid temic shunt (TIPS) is another option to con- bacterial peritonitis inhibitors alone trol refractory ascites, but its benefit should Bacterial peritonitis can be divided into may be considered be weighed against complications such as spontaneous bacterial peritonitis (SBP) and for new onset . An RCT found that secondary bacterial peritonitis. SBP is a com- mild-to-moderate TIPS with covered stents improved survival in mon in patients with cirrhosis ascites in patients patients with cirrhosis compared with regular and occurs in around 16% of hospitalized with normal renal large-volume paracentesis.42 Patients should patients, based on 1 study.48 SBP is defined function. be referred to hepatologists to make a deter- as a polymorphonuclear leukocyte count mination about TIPS placement. Widely ac- ≥ 250 cells/μL in the absence of a surgically cepted contraindications for the placement treatable source of infection.49 It is believed of TIPS are decompensated cirrhosis (Child- to be caused by bacterial translocation and Pugh > 11, model for end-stage liver disease is treated empirically with a third-­generation [MELD] > 18), renal failure (serum creatinine cephalosporin. This treatment has been > 3 mg/dL), heart failure, porto-pulmonary shown to be effective in 85% of patients.50 hypertension, and uncontrolled sepsis.43 Re- Patients with SBP are at a higher risk for current or persistent hepatic encephalopathy renal impairment, likely resulting from in- (West Haven grade ≥ 2) is also a contraindi- creased cytokine production and decreased cation. The West Haven scale is widely used circulatory volume.51 Concomitant albu- to measure severity of hepatic encephalopa- min administration has been shown to sig- thy, grading it from 1 to 4, with 1 being mild nificantly improve outcomes and to reduce encephalopathy characterized by lack of rates of in patients awareness and shorter attention span, and with serum creatinine > 1 mg/dL, blood 4 indicating unresponsiveness or coma.44 urea nitrogen > 30 mg/dL, or total bilirubin > 4 mg/dL.52 The recommended amount of How to manage albumin is 1.5 g/kg given within 6 hours of refractory ascites SBP detection and repeat administration of Fragile patients are those with refractory as- 1 g/kg on Day 3.52 cites that is either unresponsive to standard Guidelines from the American As- salt restriction and maximum-dose diuretic sociation for the Study of Liver Diseases therapy or that results in a re-accumulation and from EASL recommend the long-term of ascitic fluid soon after paracentesis.45 Spe- use of daily norfloxacin or trimethoprim-­

MDEDGE.COM/FAMILYMEDICINE VOL 70, NO 4 | MAY 2021 | THE JOURNAL OF FAMILY PRACTICE 179 sulfamethoxazole as secondary prophylaxis gan, 69% of patients with cirrhosis had at in patients who have survived an episode of least 1 nonelective readmission; 14% of pa- SBP. 18,30 Long-term antibiotic use is also justi- tients were readmitted within 1 week, and fied for primary prophylaxis in cirrhosis pa- 37% within 1 month.57 These are staggering tients who fulfill certain criteria: ascitic fluid statistics that highlight the gaps in care co- protein < 1.5 g/dL along with impaired re- ordination and management of patients with nal function (serum creatinine ≥ 1.2 mg/dL, cirrhosis in the outpatient setting. PCPs can blood urea nitrogen ≥ 25 mg/dL, or serum play a vital role in bridging this gap. sodium ≥ 130 mEq/L) or with decompen- A promising framework is suggested by sated cirrhosis (Child-Pugh score ≥ 9 and a study from Italy by Morando et al in 2013.58 bilirubin ≥ 3 mg/dL).53 It has been shown to The researchers assessed a specialized health reduce the risk of SBP and hepatorenal syn- care model for cirrhotic patients and showed drome, and improve overall survival.53 significant improvement in health care cost, readmission rate, and overall mortality when Avoid these compared with the existing model of outpa- Commonly used medications that should be tient care.58 avoided in patients with cirrhosis and ascites This was not a blinded study and there are angiotensin-converting enzyme inhibi- were concerns raised by the scientific com- tors and angiotensin receptor blockers. These munity about its design. Because it was con- Commonly used agents block the action of angiotensin, which ducted in Italy, the results might not be fully medications is a vital vasoconstrictor, and thereby cause applicable to the United States health care that should a drop in blood pressure. This has indepen- setting. However, it did show that better co- be avoided in dently been associated with poor outcomes ordination of care leads to significantly bet- patients with in patients with cirrhosis.37 ter patient outcomes and reduces health care cirrhosis and Nonsteroidal anti-inflammatory drugs expenditure. Therefore, a more complete ascites are (NSAIDs) are also relatively contraindicated understanding of the disease process and lat- angiotensin- in cirrhosis, as they can affect kidney func- est literature by PCPs, communication with converting tion, induce azotemia, and reduce kidney specialists, and comprehensive coordination enzyme sodium excretion. NSAIDs induce vasocon- of care by all parties involved is vital for the inhibitors and striction of afferent arterioles in the kidneys, management of this patient population. JFP angiotensin leading to a decreased glomerular filtration CORRESPONDENCE receptor rate, further activating RAAS and sympathet- Muhammad Salman Faisal, MD, Cleveland Clinic Foundation, blockers. ic drive. This leads to increased sodium and 9500 Euclid Avenue, Cleveland, OH 44195; [email protected] water retention and worsening ascites.54

Improve outcomes References by circling in a hepatologist 1. Runyon BA, Montano AA, Akriviadis EA, et al. The serum- ascites albumin gradient is superior to the - PCPs can play a vital role in the prevention, concept in the of ascites. Ann Intern Med. treatment, surveillance, and home care of 1992;117:215-220. 2. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prog- patients with cirrhosis who are at risk for nostic indicators of survival in cirrhosis: a systematic review of ascites.55 Referral of patients with hepatic 118 studies. J Hepatol. 2006;44:217-231. 3. Gordon FD. Ascites. Clin Liver Dis. 2012;16:285-299. impairment manifesting as unexplained ab- 4. Schrier RW, Arroyo V, Bernardi M, et al. Peripheral arterial vaso- normal liver function tests, new-onset asci- dilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151-1157. tes, and/or image findings consistent with 5. Arroyo V, Terra C, Gines P. Advances in the pathogenesis and cirrhosis to a hepatologist at least once is rec- treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol. 2007;46:935-946. ommended. Such referrals have been shown 6. Bernardi M, Moreau R, Angeli P, et al. Mechanisms of decom- to be associated with a better overall out- pensation and organ failure in cirrhosis: from peripheral arte- rial vasodilation to systemic inflammation hypothesis. J Hepatol. 56 come. Patients with known cirrhosis leading 2015;63:1272-1284. to ascites can generally be managed at home 7. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrho- sis: a position statement based on the EASL Special Conference with the assistance of specialists and special- 2013. J Hepatol. 2014;60:1310-1324. ized nurses.35 8. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated im- mune dysfunction: distinctive features and clinical relevance. In a study from the University of Michi- J Hepatol. 2014;61:1385-1396.

180 THE JOURNAL OF FAMILY PRACTICE | MAY 2021 | VOL 70, NO 4 ASCITES IN CIRRHOSIS

9. Oey RC, van Buuren HR, de Man RA. The diagnostic work-up in 35. Grattagliano I, Ubaldi E, Bonfrate L, et al. Management of liver patients with ascites: current guidelines and future prospects. cirrhosis between primary care and specialists. World J Gastroen- Neth J Med. 2016;74:330-335. terol. 2011;17:2273-2282. 10. de Kerguenec C, Hillaire S, Molinié V, et al. Hepatic manifesta- 36. Pockros PJ, Reynolds TB. Rapid diuresis in patients with ascites tions of hemophagocytic syndrome: a study of 30 cases. Am from chronic liver disease: the importance of . J Gastroenterol. 2001;96:852-857. Gastroenterology. 1986;90:1827-1833. 11. Milić S, Lulić D, Štimac D. Non-alcoholic fatty liver disease and 37. EASL clinical practice guidelines on the management of ascites, obesity: biochemical, metabolic and clinical presentations. spontaneous bacterial peritonitis, and hepatorenal syndrome in World J Gastroenterol. 2014;20:9330-9337. cirrhosis. J Hepatol. 2010;53:397-417. 12. Aron-Wisnewsky J, Clement K, Pépin J-L. Nonalcoholic fatty 38. Gines P, Arroyo V, Quintero E, et al. Comparison of paracente- liver disease and obstructive sleep apnea. Metabolism. 2016;65: sis and diuretics in the treatment of cirrhotics with tense asci- 1124-1135. tes. Results of a randomized study. Gastroenterology. 1987;93: 13. Li CP, Lee FY, Hwang SJ, et al. Spider angiomas in patients with 234-241. liver cirrhosis: role of alcoholism and impaired liver function. 39. Salerno F, Badalamenti S, Incerti P, et al. Repeated paracentesis Scand J Gastroenterol. 1999;34:520-523. and i.v. albumin infusion to treat ‘tense’ ascites in cirrhotic pa- 14. Cavanaugh J. Gynecomastia and cirrhosis of the liver. Arch Intern tients. A safe alternative therapy. J Hepatol. 1987;5:102-108. Med. 1990;150:563-565. 40. Sola R, Vila MC, Andreu M, et al. Total paracentesis with dextran 15. Karnath B. Stigmata of chronic liver disease. Hosp Phys. 40 vs diuretics in the treatment of ascites in cirrhosis: a random- 2003;7:14-16,28. ized controlled study. J Hepatol. 1994;20:282-288. 16. Schipper HG, Godfried MH. [Physical diagnosis--ascites]. Ned 41. Bernardi M, Caraceni P, Navickis RJ, et al. Albumin infusion in pa- Tijdschr Geneeskd. 2001;145:260-264. tients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012;55:1172-1181. 17. Cattau EL, Jr., Benjamin SB, Knuff TE, et al. The accuracy of the in the diagnosis of suspected ascites. 42. Bureau C, Thabut D, Oberti F, et al. Transjugular intrahepatic JAMA. 1982;247:1164-1166. portosystemic shunts with covered stents increase transplant- 18. EASL clinical practice guidelines for the management of patients free survival of patients with cirrhosis and recurrent ascites. Gas- troenterology. 2017;152:157-163. with decompensated cirrhosis. J Hepatol. 2018;69:406-460. 19. Runyon BA, AASLD Practice Guidelines Committee. Manage- 43. Fagiuoli S, Bruno R, Debernardi Venon W, et al. Consensus con- ment of adult patients with ascites due to cirrhosis: an update. ference on TIPS management: techniques, indications, contrain- Hepatology 2009;49:2087-2107. dications. Dig Liver Dis. 2017;49:121-137. 20. EASL Clinical practice guidelines: management of hepatocellular 44. Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopa- NSAIDs are carcinoma. J Hepatol. 2018;69:182-236. thy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congress- relatively 21. Runyon BA. Care of patients with ascites. New Engl J Med. es of Gastroenterology, Vienna, 1998. Hepatology. 2002;35: contraindicated 1994;330:337-342. 716-721. 22. Sakai H, Sheer TA, Mendler MH, et al. Choosing the loca- 45. Salerno F, Guevara M, Bernardi M, et al. Refractory ascites: in cirrhosis as tion for non-image guided abdominal paracentesis. Liver Int. pathogenesis, definition and therapy of a severe complication in they can affect 2005;25:984-986. patients with cirrhosis. Liver Int. 2010;30:937-947. 23. Mercaldi CJ, Lanes SF. Ultrasound guidance decreases complica- 46. Caraceni P, Riggio O, Angeli P, et al. Long-term albumin admin- kidney function, tions and improves the cost of care among patients undergoing istration in decompensated cirrhosis (ANSWER): an open-label induce azotemia, thoracentesis and paracentesis. Chest. 2013;143:532-538. randomised trial. Lancet. 2018;391:2417-2429. 24. Ennis J, Schultz G, Perera P, et al. Ultrasound for detection of as- 47. Solà E, Solé C, Simón-Talero M, et al. Midodrine and albumin and reduce cites and for guidance of the paracentesis procedure: technique for prevention of complications in patients with cirrhosis await- kidney sodium and review of the literature. Int J Clin Med. 2014;5:1277-1293. ing liver transplantation. A randomized placebo-controlled trial. 25. Runyon BA, Canawati HN, Akriviadis EA. Optimization of ascitic J Hepatol. 2018;69:1250-1259. excretion. fluid culture technique. Gastroenterology. 1988;95:1351-1355. 48. Fasolato S, Angeli P, Dallagnese L, et al. Renal failure and bacte- 26. Akriviadis EA, Runyon BA. Utility of an algorithm in differentiat- rial infections in patients with cirrhosis: epidemiology and clini- ing spontaneous from secondary bacterial peritonitis. Gastroen- cal features. Hepatology. 2007;45:223-229. terology 1990;98:127-133. 49. Hoefs JC, Canawati HN, Sapico FL, et al. Spontaneous bacterial 27. Hoefs JC. Serum protein concentration and portal pressure de- peritonitis. Hepatology. 2007;2:399-407. termine the ascitic fluid protein concentration in patients with 50. Felisart J, Rimola A, Arroyo V, et al. Cefotaxime is more effective chronic liver disease. J Lab Clin Med. 1983;102:260-273. than is ampicillin-tobramycin in cirrhotics with severe infections. 28. Farias AQ, Silvestre OM, Garcia-Tsao G, et al. Serum B-type na- Hepatology. 1985;5:457-462. triuretic peptide in the initial workup of patients with new on- 51. Lenz K, Kapral C, Gegenhuber A, et al. Systemic, renal, and set ascites: a diagnostic accuracy study. Hepatology. 2014;59: hepatic hemodynamic derangement in cirrhotic patients 1043-1051. with spontaneous bacterial peritonitis. Hepatology. 2004;39: 29. Gupta R, Misra SP, Dwivedi M, et al. Diagnosing ascites: value 865-866. of ascitic fluid total protein, albumin, cholesterol, their ratios, 52. Sigal SH, Stanca CM, Fernandez J, et al. Restricted use of albumin serum-ascites albumin and cholesterol gradient. J Gastroenterol for spontaneous bacterial peritonitis. Gut. 2007;56:597-599. Hepatol. 1995;10:295-299. 30. Runyon BA. Management of adult patients with ascites due to 53. Fernández J, Navasa M, Planas R, et al. Primary prophylaxis cirrhosis: update 2012. AASLD Practice Guideline. Accessed of spontaneous bacterial peritonitis delays hepatorenal syn- April 28, 2021. www.aasld.org/sites/default/files/2019-06/ drome and improves survival in cirrhosis. Gastroenterology. AASLDPracticeGuidelineAsciteDuetoCirrhosisUpdate2012 2007;133:818-824. Edition4_.pdf 54. Boyer TD, Zia P, Reynolds TB. Effect of indomethacin and pros- 31. Morando F, Rosi S, Gola E, et al. Adherence to a moderate sodium taglandin A1 on renal function and plasma renin activity in alco- restriction diet in outpatients with cirrhosis and ascites: a real-life holic liver disease. Gastroenterology. 1979;77:215-222. cross-sectional study. Liver Int. 2015;35:1508-1515. 55. Grattagliano I, Ubaldi E, Portincasa P, et al. Liver disease: early 32. Bernardi M, Laffi G, Salvagnini M, et al. Efficacy and safety of signs you may be missing. J Fam Pract. 2009;58:514-521. the stepped care medical treatment of ascites in liver cirrhosis: 56. Bini EJ, Weinshel EH, Generoso R, et al. Impact of gastroenter- a randomized controlled clinical trial comparing two diets with ology consultation on the outcomes of patients admitted to the different sodium content. Liver. 1993;13:156-162. hospital with decompensated cirrhosis. Hepatology. 2001;34: 33. Angeli P, Fasolato S, Mazza E, et al. Combined versus sequen- 1089-1095. tial diuretic treatment of ascites in non-azotaemic patients 57. Volk ML, Tocco RS, Bazick J, et al. Hospital readmissions among with cirrhosis: results of an open randomised clinical trial. Gut. patients with decompensated cirrhosis. Am J Gastroenterol. 2010;59:98-104. 2012;107:247-252. 34. Santos J, Planas R, Pardo A, et al. alone or in com- 58. Morando F, Maresio G, Piano S, et al. How to improve care in bination with furosemide in the treatment of moderate ascites in outpatients with cirrhosis and ascites: a new model of care nonazotemic cirrhosis. A randomized comparative study of effi- coordination by consultant hepatologists. J Hepatol. 2013;59: cacy and safety. J Hepatol. 2003;39:187–192. 257-264.

MDEDGE.COM/FAMILYMEDICINE VOL 70, NO 4 | MAY 2021 | THE JOURNAL OF FAMILY PRACTICE 181

Top View