Review

Optimizing in Adult Patients With Liver Disease and Liver Transplantation Yoona Rhee, M.D., Sc.M., Beverly E. Sha, M.D., and Carlos A.Q. Santos, M.D., M.P.H.S.

KEY TAKE-HOME POINTS safety profiles. -9 can now be given to adults up to 45 years old. • Travel-related health counseling and vaccination in pa- • Clinicians should actively vaccinate patients with LD and tients with LD and LT recipients is crucial and should be following LT to reduce -preventable illnesses. performed months prior to anticipated travel. • Early vaccination prior to progression of LD and prior to LT provides the best chance of optimal vaccine response. • are safe; however, live vaccines should not Patients with end-stage liver disease (ESLD) and LT re- be provided in immunosuppressed patients with LD or cipients remain at high risk for vaccine-preventable infec- 1-3 after liver transplant (LT) because of risk for secondary tions in the pre- and post-LT period. Despite higher risks, disseminated disease. Transplant candidates should vaccine adherence remains low.4-6 Timing of vaccination not receive live vaccines within 4 weeks of antici­pated remains crucial, because immunological responses are LT. anticipated to be optimal in early liver disease (LD) and • Heplisav-B and Shingrix are new inactivated recombi- prior to LT7; therefore, every effort should be made to im- nant vaccines with improved immunogenicity and better munize prior to transplantation when possible. Guidelines

Abbreviations: ACIP, Advisory Committee on Practices; AST, American Society of Transplantation; CDC, Centers for Disease Control and Prevention; CLD, chronic liver disease; ESLD, end-stage liver disease; FDA, US Food and Drug Administration; HAV, hepatitis A virus; HBV, hepatitis B virus; HPV, human papillomavirus; HZ, herpes zoster; IDSA, Infectious Diseases Society of America; IgG, immunoglobulin G; JEV, Japanese encephalitis virus; LD, liver disease; LT, liver transplantation; MenACWY, meningococcal ACWY; MMR, measles, mumps, and rubella; RZV, recombinant herpes zoster; SOT, solid organ transplantation; Tdap, tetanus, diphtheria, pertussis; VZV, . From the Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, IL. Potential conflict of interest: Nothing to report. Received August 4, 2019; accepted November 2, 2019.

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63 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD Review Vaccines: Liver Disease and Transplantation Rhee, Sha, and Santos 9,28 HAV IgG HAV 27 LT should be checked in high-risk should be checked with con - travelers) patients (i.e., doses. of booster sideration suboptimal responses to two two to suboptimal responses may occur vaccine doses of HAV recipients. in transplant contraindicated after LT. Provide Provide LT. after contraindicated (see RZV vaccine inactivated earlier). Yes. Same as for CLD/ESLD. Same as for Yes. CLD/ESLD. Same as for Yes. ESLD/CLD. Same as for Yes. CLD/ESLD. Same as for Yes. CLD/ESLD. Same as for Yes. Yes. Same as for CLD/ESLD. Same as for Yes. Yes. Same as for CLD/ESLD. Same as for Yes. Yes. Same as for CLD/ESLD. However, However, CLD/ESLD. Same as for Yes. No. Live vaccines are generally generally are vaccines Live No. 32 Given as two-dose as two-dose Given † Check HBV surface IgG antibody Check HBV surface CLD/ESLD 29-31 at least 1 month after vaccination; if remains nonresponder, nonresponder, if remains vaccination; at least 1 month after vaccination dose or repeat consider one-time booster vaccine IgG antibody is detected, HBV core If isolated series. reason. depends on suspected consideration Protects and 6 months. 1-2, series at 0, in three-dose Given and 58. 52, 45, 33, 31, 18, 16, 11, 6, against nine serotypes: months. ≥1 year Should be given during childhood primary series. if both PCV13 first give is to so preference PPSV23, after needed (see later). dose old and a final 2 doses at <65 years Up to ≥5 years. optimal PCV13 for after ≥8 weeks Give old. at ≥65 years (see earlier). antibody response is desired, If pertussis protection 10 years. every booster Tdap Td and last between time interval is no minimum there administration. or prior or disease. or prior chickenpox series at 0 and 2-6 months. should be given at 0 and 6-12 months. The CDC does not at 0 and 6-12 months. should be given because serology checking postvaccination recommend standard no current are there good, is generally response may not be sensitive and tests recommendations, booster antibodies. protective low-level detect enough to in the blood. Recommend Heplisav-B at 0 and 1 month. Recommend Heplisav-B at 0 and 1 month. in the blood. 40 μ g/mL Engerix-B/Recombivax-B are Alternatives and 2, 1, (0, and 6) or accelerated 1, (0, at standard 12 months) schedules. immunogenicity. better to Yes. Recommend for adult men and women up to 45 years old. old. 45 years up to adult men and women Recommend for Yes. during the fall-winter once yearly Should be received Yes. if not received once as an adult, Should be received Yes. by doses separated lifetime three up to Can receive Yes. Td by followed once, should be provided Tdap vaccine Yes. Yes. Recommend if ≥50 years old, regardless of VZV serostatus VZV serostatus of regardless old, Recommend if ≥50 years Yes. Yes. If HAV IgG antibody is not detected in the blood, two doses two in the blood, IgG antibody is not detected If HAV Yes. Yes. Indicated if HBV surface IgG antibody is not detected IgG antibody is not detected if HBV surface Indicated Yes. (Shingrix) due vaccine inactivated Recommend the newer No. 8,9,13 T AN D L 23 Clinical Description CC INES IN C L D/ ESL D VA high mutation rates, seasonal vaccine will try to match a will try seasonal vaccine to rates, high mutation strains. circulating combination of the most likely PCV13 disease. and other invasive meningitis, pneumonia, 14, 9V, 7F, 6B, 6A, 5, 4, 3, 1, against 13 serotypes: protects and 23F. 19F, 19A, 18C, 14, 12F, 11A, 10A, 9V, 9N, 8, 7F, 6B, 5, 4, 3, 2, 1, and 33F. serotypes: 23F, 22F, 20, 19A, 19F, 18C, 17F, 15B, Diphtheria is caused by . Clostridium tetani the bacteria diphtheria and causes Corynebacterium the bacteria The bacteria disease. or other invasive respiratory otherwise as known pertussis causes pertussis, Bordetella “whooping cough”. (VZV) . Shingles can cause a painful local (VZV) infection. or disseminate. rash vesicular (genitourinary, anal, oropharyngeal), but it can also cause oropharyngeal), anal, (genitourinary, may be worse after Prognosis warts. common and genital because of . LT cause severe acute LD. acute cause severe or chronic infection. There is a risk for hepatocellular hepatocellular is a risk for There infection. or chronic disease. in chronic carcinoma Both influenza A and B viruses can cause infection. Due to Due to A and B viruses can cause infection. Both influenza that can cause pneumoniae is a bacteria Streptococcus against 23 PPSV23 protects Another . that is caused by infection is a nervous system Tetanus Shingles (HZ) disease is a reactivation of prior chickenpox of prior chickenpox Shingles (HZ) disease is a reactivation The most feared complication of HPV infection is malignancy complication of HPV infection The most feared HAV can be acquired by fecal-oral transmission and can transmission fecal-oral by can be acquired HAV Another vaccine to prevent shingles disease (see earlier). prevent to Another vaccine HBV is a blood-borne pathogen that causes acute and/ HBV is a blood-borne pathogen that causes acute (PPSV23) Boostrix Recombivax-HB, Recombivax-HB, Heplisav-B (HepB-CpG) Brand Name(s) Brand Multiple (PCV-13) Prevnar Pneumovax Adacel, Tenivac, Shingrix Gardasil-9 Havrix, Vaqta Havrix, Zostavax Engerix-B, Engerix-B, re COMM EN D E R OUT INE conjugate polysaccharide pertussis ria, Tdap) (Td, Zoster (ZVL) Zoster ‡ Influenza virus Influenza Pneumococcal Pneumococcal diphthe - Tetanus, RZV HPV HAV* HBV* Herpes Live A B LE 1 . Live Inactivated T Vaccine

64 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD Review Vaccines: Liver Disease and Transplantation Rhee, Sha, and Santos

recommend inactivated vaccines to be given 2 weeks and live vaccines 4 weeks prior to LT to maximize response and safely proceed with immunosuppression.8,9 After LT, rec- ommendations are to wait 3-6 months when immunosup- pression is at maintenance, except inactivated influenza LT vaccine, which can be given effectively 1 month after LT.9,10 Vaccines should not be given during treatment for acute rejection, because increased immunosuppression may contraindicated after LT. Provide Provide LT. after contraindicated (see vaccine influenza inactivated earlier). contraindicated after LT. after contraindicated contraindicated after LT. after contraindicated blunt vaccine response.9 Live vaccines should be avoided No. Live vaccines are generally generally are vaccines Live No. No. Live vaccines are generally generally are vaccines Live No. No. Live vaccines are generally generally are vaccines Live No. in immunosuppressed patients with LD and after LT.8,9 Although there are theoretical risks of rejection with vac- cination after solid organ transplantation (SOT; e.g., non- specific immune activation or induction of T/B-lymphocyte responses against alloantigens), there are no clinical data Recommend

33 to support this concern.11,12 Therefore, vaccination in patients with LD and LT far outweigh any potential risk and should be encouraged.

CLD/ESLD Routine vaccine schedules recommended for patients with LD and LT recipients are noted in Table 1, accord- ing to the Infectious Diseases Society of America (IDSA), American Society of Transplantation (AST) Infectious Note that CDC recommends two doses separated by by doses separated two that CDC recommends Note Do not recheck serology; may be unreliable to detect detect to may be unreliable serology; Do not recheck § ‖ Diseases Community of Practice, and the Centers for for advanced LD. Consider timing if LT Consider timing if LT LD. advanced for vaccine inactivated anticipated. dose. ≥4 weeks with no follow-up serology. Consider timing if LT Consider timing if LT serology. with no follow-up ≥4 weeks anticipated. protection. Consider timing if LT anticipated. Consider timing if LT protection. at serology one dose and recheck provide not detected; second provide undetectable, remains antibody If 4-8 weeks. dose. provide significant benefit over inactivated vaccine, with vaccine, inactivated over benefit significant provide efficacy. comparative possible reduced Disease Control and Prevention (CDC) Advisory Committee Yes. If MMR IgG antibodies are not detected, provide one provide not detected, If MMR IgG antibodies are Yes. Yes. Recommend if ≤50 years old and VZV IgG antibody old and Recommend if ≤50 years Yes. Maybe, for healthy adults ≤50 years old. However, unlikely to to unlikely However, old. adults ≤50 years healthy for Maybe, on Immunization Practices (ACIP).8,9,13 Regardless of prior vaccination, pretransplant serologies should be obtained for hepatitis A virus (HAV), hepatitis B virus (HBV), varicella zoster virus (VZV), and measles. A few vaccines are worth mentioning. Heplisav-B (HepB-CpG/HBsAg-1018; Dynavax Technologies, Berkeley, CA, USA) is a yeast-derived recom- binant vaccine against HBV, which was approved by the US Food and Drug Administration (FDA) in November 2017. The superiority of HepB-CpG/HBsAg-1018 over existing standard dose (20 g/mL) conventional recombinant vac- Clinical Description μ cine was demonstrated in several phase 3 studies, with a seroprotection rate (defined as the proportion of adults with hepatitis B surface antibody titer ≥10 mIU/mL) of 14-16

cause severe disease. The recent resurgence of measles resurgence The recent disease. cause severe immunization. highlights the need for and mumps 90% to 95%, compared to 65% to 81%, respectively. Measles, mumps and rubella are viral illnesses that may viral and rubella are mumps Measles, Primary VZV infection causes chickenpox. VZV infection Primary Another vaccine to prevent influenza infection (see earlier). infection influenza prevent to Another vaccine Shingrix (GlaxoSmithKline, King of Prussia, PA, USA) is an inactivated adjuvanted recombinant against herpes zoster (HZ) infection, which was approved by the FDA in October 2017 for use in adults ≥50 years old. In phase 3 studies, vaccine efficacy rate ranged from Brand Name(s) Brand M-M-R II Varivax FluMist 96.6% to 97.9% for the prevention of HZ infection after a mean of 3.2 years, and high protection rates were sus- tained for adults ≥70 years old with a pooled vaccine effi- CO N T IN U E D cacy rate of 91.3%.17,18 Prior to the approval of Shingrix, ACIP recommendations. when available. Live An equivalent inactivated vaccine is preferred considered. Risks and benefits of live vaccines in patients with advanced LD decompensated cirrhosis should be carefully ACIP recommendations. AST recommendations. g/mL) that should be provided as a three-dose series at 0, 1, and 6 months. as a three-dose the combination vaccine (contains Engerix-B 20 μ g/mL) that should be provided and HBV vaccines may be substituted by Twinrix, *Individual HAV † ‡ § ‖ only a live attenuated HZ vaccine was available that, in the MMR VZV Influenza virus Influenza A B LE 1 . vaccines are contraindicated in immunosuppressed patients with LD. contraindicated in immunosuppressed vaccines are T Vaccine Shingles Prevention Study, was associated with a 37.6%

65 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD Review Vaccines: Liver Disease and Transplantation Rhee, Sha, and Santos LT immunocompromised hosts, a fifth a fifth hosts, immunocompromised is vaccination dose of postexposure at day 28. recommended contraindicated after LT. Travel to to Travel LT. after contraindicated fever with yellow endemic regions should be avoided. tenuated vaccine used in Asia (SA used in vaccine tenuated 14-14-2) is contraindicated. contraindicated after LT. after contraindicated contraindicated after LT. Provide Provide LT. after contraindicated (see inactivated earlier). Yes. Same as for CLD/ESLD. Same as for Yes. Yes. Same as for CLD/ESLD. In CLD/ESLD. Same as for Yes. No. Live vaccines are generally generally are vaccines Live No. Yes. Same as for CLD/ESLD. Same as for Yes. Yes. Same as for CLD/ESLD. A live at - A live CLD/ESLD. Same as for Yes. No. Live vaccines are generally generally are vaccines Live No. No. Live vaccines are generally generally are vaccines Live No. Yes. Same as for CLD/ESLD. Same as for Yes. Four oral capsule doses on days oral Four 34 CLD/ESLD , at least 2 weeks prior to travel to develop immunity. immunity. develop to travel prior to at least 2 weeks injection, if ongoing risk. 2 years dose every Booster are given as a three-dose (0, 7, and 21-28 days) 7, (0, as a three-dose given are vaccinations respectively. and 14 days) series, 7, 3, (0, or a four-dose travelers long-term for is indicated vaccination Pre-exposure from and/or remote planned animal contact, (≥1 month), may be 2 years 6 months to doses every Booster medical care. high-risk individuals at ongoing risk to in certain recommended serum titers. appropriate maintain inactivated vaccine if advanced LD, due to better safety profile profile safety better due to LD, if advanced vaccine inactivated efficacy. and comparable immunity. Potential rare but serious adverse events include but serious adverse events rare Potential immunity. and disease (YEL-AVD) viscerotropic vaccine-associated is Consider timing if LT disease (YEL-AND). neurological anticipated. ceived, three doses total at 0 and 1-2 months, followed by by followed at 0 and 1-2 months, doses total three ceived, candi - adults are Vaccinated second dose. 6-12 months after high-risk region. to if traveling booster one lifetime for dates is recommended for long-term travelers (≥1 month) or those travelers long-term for is recommended Consider travel. rural or extensive frequent with short-term risk and primary dose if at continued series received booster prior. ≥1 year dose should be received ≤10 days prior to potential exposure. potential ≤10 days prior to dose should be received 1, 3, 5, and 7. Last dose should be ≥1 week prior to travel to to travel prior to Last dose should be ≥1 week and 7. 5, 3, 1, if ongoing risk. 5 years dose every Booster immunity. develop anticipated. Consider timing if LT belt of sub-Saharan African and prior to Saudi Arabia travel for for travel Arabia Saudi African and prior to belt of sub-Saharan doses at 0 two If primary series not received, . Hajj or Umrah risk for if continued 5 years every and ≥2 months with booster exposure. Yes, for travel to rural areas of tropical countries. One-dose countries. of tropical areas rural to travel for Yes, Yes, if potential risk for exposure. Pre-exposure and postexposure and postexposure Pre-exposure exposure. risk for if potential Yes, Maybe, for travel to rural areas of tropical countries. Recommend countries. of tropical areas rural to travel for Maybe, Yes, if traveling to endemic areas. One dose provides lifelong lifelong One dose provides endemic areas. to if traveling Yes, - If primary series not re high-risk areas. to travel for Yes, Yes, for travel to endemic areas. Two-dose series at 0 and 28 days Two-dose endemic areas. to travel for Yes, Yes, for travel to areas of active cholera transmission. One oral One oral transmission. cholera of active areas to travel for Yes, Yes, for travel to high endemicity areas such as the meningitis high endemicity areas to travel for Yes, T AN D L Clinical Description CC INES IN C L D/ ESL D VA and is transmitted by the fecal-oral route. Fever Fever route. the fecal-oral by typhi and is transmitted but most common, disease/diarrhea are and intestinal Endemic worldwide disease can occur. extraintestinal with poor areas in low-resource but most prominent sanitation. neurotropic lyssaviruses. Prevalent in all continents, except except in all continents, Prevalent lyssaviruses. neurotropic dogs and wild animals. by transmitted Antarctica; to Africa and South America. It causes viral hemorrhagic It causes viral America. Africa and South to failure. multiorgan and can lead to fever by fecal-oral and pharyngeal route. Endemic in certain Endemic in certain and pharyngeal route. fecal-oral by parts of Africa and Asia. the Western Pacific. It causes neuroinvasive disease. It causes neuroinvasive Pacific. Western the watery diarrhea and dehydration with electrolyte wasting. with electrolyte diarrhea and dehydration watery can lead to meningitis and disseminated infection infection meningitis and disseminated can lead to protects MenACWY (meningococcemia) with shock. Y. and W, C, A, serogroups: against four Typhoid (enteric) fever is caused by the bacteria the bacteria is caused by fever (enteric) Typhoid Rabies is a neuroinvasive infection caused by several several caused by infection Rabies is a neuroinvasive Another vaccine to prevent typhoid fever (see earlier). typhoid fever prevent to Another vaccine Yellow fever virus is transmitted by mosquitos and is endemic is and mosquitos by transmitted is virus fever Yellow Poliovirus causes neuroinvasive disease and is transmitted disease and is transmitted causes neuroinvasive Poliovirus JEV is transmitted by mosquitos and is endemic to Asia and and is endemic to mosquitos by JEV is transmitted can lead to severe severe can lead to Vibrio cholerae with the bacteria Infection Infection with the bacteria Neisseria meningitides with the bacteria Infection (intramuscular) combination vaccines Brand Name(s) Brand Typhim Vi Typhim Imovax, RabAvert Imovax, Vivotif (oral) Vivotif YF-Vax Ipol, multiple multiple Ipol, Ixiaro Vaxchora (oral) Vaxchora Menactra, Menveo Menactra, † T RAVEL re COMM EN D E Additional indication for includes asplenic patients, who should receive both MenACWY and MenB (Bexsero, Trumenba). both MenACWY and MenB (Bexsero, Additional indication for meningococcal vaccine includes asplenic patients, who should receive when available. Live An equivalent inactivated vaccine is preferred considered. Risks and benefits of live vaccines in patients with advanced LD decompensated cirrhosis should be carefully typhoid poliovirus (IPV) poliovirus *Anthrax, oral poliovirus, and smallpox vaccines are not readily available in United States. not readily *Anthrax, oral poliovirus, and smallpox vaccines are † ‡ ‡ Inactivated Inactivated Rabies MenACWY Live typhoid Live Yellow fever virus fever Yellow Inactivated Inactivated JEV Cholera A B LE 2 . Live vaccines are contraindicated in immunosuppressed patients with LD. contraindicated in immunosuppressed vaccines are Inactivated T Vaccine*

66 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD Review Vaccines: Liver Disease and Transplantation Rhee, Sha, and Santos reduction in the of HZ infection in subjects who 600 South Paulina Street, Suite 143, Chicago, IL 60612. E-mail: were ≥70 years old.19 Although immunosuppressed pa- [email protected] tients were excluded from all of the aforementioned phase REFERENCES 3 studies, demonstrated efficacy of the new HBV and HZ 1) Pagliano P, Boccia G, De Caro F, et al. Bacterial meningitis complicat- vaccines in patients with expected decreased immuniza- ing the course of liver cirrhosis. Infection 2017;45:795-800. tion response (e.g., diabetes mellitus, stem cell transplan- tation16,20) shows promise for improved immunogenicity in 2) Keeffe EB. Acute hepatitis A and B in patients with chronic liver disease: Prevention through vaccination. Am J Medi 2005;118 patients with LD and LT recipients, as compared with older (Suppl. 10A):21S-27S. vaccine preparations. Lastly, in October 2018, the FDA ap- proved the expanded use of Gardasil-9 (Merck & Co., Inc., 3) Martin ST, Torabi MJ, Gabardi S. Influenza in solid organ transplant recipients. Ann Pharmacother 2012;46:255-264. Kenilworth, NJ, USA), a recombinant vaccine against nine serotypes of human papillomavirus (HPV), to include men 4) Williams WW, Lu PJ, O’Halloran A, et al. Surveillance of vaccination and women up to 45 years old.21 Studies on use of HPV coverage among adult populations—United States, 2015. MMWR Surveill Summ 2017;66:1-28. vaccine in patients with LD or LT recipients are limited and suggest suboptimal serological response, with one study 5) Tajammal R, Ali IA, Syed T, Nusrat S. Immunization against hepatitis of 50 SOT recipients who received the quadrivalent HPV a virus and hepatitis b virus in patients with chronic liver disease: Are we doing a good job? Cureus 2018;10:e2528. vaccine resulting in 52.6% to 68.4% serological response against the four serotypes.22 Nonetheless, SOT recip- 6) Weltermann B, Herwig A, Dehnen D, Herzer K. Vaccination status ients remain at high risk for HPV-associated malignancy, of pneumococcal and other vaccines in 444 liver transplant pa- tients compared to a representative population sample. Ann Trans and all eligible adults up to 45 years old should undergo 2016;21:200-207. vaccination.23 7) Andersson D, Castedal M, Friman V. Are liver transplant recipients Patients with LD and LT recipients who wish to travel protected against hepatitis A and B? Trans Proc 2013;45:1193-1197. should be evaluated months in advance by a travel clinic. 8) Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice In addition to vaccination, extensive counseling should guideline for vaccination of the immunocompromised host. Clin be provided on destination-specific safe travel behaviors, Infect Dis 2014;58:e44-e100. food safety, minimizing exposure to endemic , 9) Danziger-Isakov L, Kumar D;AST ID Community of Practice. prophylaxis for traveler’s diarrhea and malaria (and inter- Vaccination of solid organ transplant candidates and recipients: actions with transplant rejection medications), insect pro- Guidelines from the American society of transplantation infectious tection, and posttravel care.24,25 Routine vaccines should diseases community of practice. Clin Transplant 2019;33:e13563. be updated, with particular focus on HAV, HBV, tetanus, 10) Perez-Romero P, Bulnes-Ramos A, Torre-Cisneros J, et al. Influenza diphtheria, pertussis (Tdap), and measles, mumps, and ru- vaccination during the first 6 months after solid organ transplan- bella (MMR) vaccines. Table 2 lists the most common travel tation is efficacious and safe. Clin Microbiol Infect 2015;21:1040. e11-1040.e18. vaccines that may be indicated in patients with LD and LT recipients, as recommended by the AST and ACIP.24 The 11) Lawal A, Basler C, Branch A, et al. Influenza vaccination in orthot- CDC Yellow Book provides additional in-depth information opic liver transplant recipients: Absence of post administration ALT elevation. Am J Transplant 2004;4:1805-1809. about travel health and infection prevention.26 12) Mulley WR, Dendle C, Ling JEH, et al. Does vaccination in solid- In conclusion, vaccine optimization in patients with organ transplant recipients result in adverse immunologic sequelae? LD and LT recipients is integral to the prevention of many A systematic review and meta-analysis. J Heart Lung Transplant 2018;37:844-852. https​://doi.org/10.1016/j.healun.2018.03.001. communicable diseases. Vaccination should ideally occur in early LD and prior to LT, especially for live vaccines that 13) Kim DK, Hunter P. Advisory Committee on Immunization Practices are contraindicated after LT. Comprehensive counseling on recommended immunization schedule for adults aged 19 years or older—United States, 2019. MMWR Morb Mortal Wkly Rep travel health and vaccinations should be provided for trav- 2019;68:115-118. elers who are LT candidates and recipients. 14) Heyward WL, Kyle M, Blumenau J, et al. Immunogenicity and CORRESPONDENCE safety of an investigational with a Toll-like re- ceptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed Yoona Rhee, M.D., Sc.M., Division of Infectious Diseases, hepatitis B vaccine in healthy adults 40-70 years of age. Vaccine Department of Internal Medicine, Rush University Medical Center, 2013;31:5300-5305.

67 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD Review Vaccines: Liver Disease and Transplantation Rhee, Sha, and Santos

15) Halperin SA, Ward B, Cooper C, et al. Comparison of safety and Transplantation Infectious Diseases Community of Practice. Clin immunogenicity of two doses of investigational hepatitis B virus sur- Transplant 2019;33:e13529. face antigen co-administered with an immunostimulatory phospho- rothioate oligodeoxyribonucleotide and three doses of a licensed 25) Clemente WT, Pierrotti LC, E, et al. Recommendations for hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine management of endemic diseases and travel medicine in solid- 2012;30:2556-2563. organ transplant recipients and donors: Latin America. Transplantation 2018;102:193-208. 16) Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like 26) Centers for Disease Control and Prevention. CDC Yellow Book receptor 9 agonist adjuvant compared with a licensed hepatitis B 2018: Health Information for International Travel. New York: Oxford vaccine in adults. Vaccine 2018;36:668-674. University Press; 2017.

17) Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adju- 27) Jeon HJ, Ro H, Jeong JC, et al. Efficacy and safety of hepatitis A vanted herpes zoster subunit vaccine in older adults. N Eng J Med vaccination in kidney transplant recipients. Transpl Infect Dis 2015;372:2087-2096. 2014;16:511-515.

18) Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster 28) Zuckerman JN, Connor BA, von Sonnenburg F. Hepatitis A and B subunit vaccine in adults 70 years of age or older. N Engl J Med booster recommendations: Implications for travelers. Clin Infect Dis 2016;375:1019-1032. 2005;41:1020-1026.

19) Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent her- 29) Minakari M, Tahmasebi A, Motlagh MH, et al. Efficacy of double pes zoster and in older adults. N Engl J Med dose recombinant hepatitis B vaccination in chronic hepatitis C 2005;352:2271-2284. patients, compared to standard dose vaccination. Int J Prev Med 2014;5:145-151. 20) Bastidas A, de la Serna J, El Idrissi M, et al. Effect of recombi- nant zoster vaccine on incidence of herpes zoster after autolo- 30) Dominguez M, Barcena R, Garcia M, et al. Vaccination against hep- gous stem cell transplantation: A randomized . JAMA atitis B virus in cirrhotic patients on liver transplant waiting list. Liver 2019;322:123-133. Transplant 2000;6:440-442.

21) US Food and Drug Administration. Gardasil 9. Available at: https​ 31) Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B ://www.fda.gov/vacci​nes-blood-biolo​gics/vacci​nes/garda​sil-9. virus infection in the United States: Recommendations of the ad- Published October 5, 2018. Accessed July 14, 2019. visory committee on immunization practices. MMWR Recomm Rep 2018;67:1-31. 22) Kumar D, Unger ER, Panicker G, et al. Immunogenicity of quadri- valent human papillomavirus vaccine in organ transplant recipients. 32) Piroth L, Launay O, Miailhes P, et al. Patients with isolated hepatitis Am J Transplant 2013;13:2411-2477. B core antibody: Has the time come to vaccinate? Clin Infect Dis 2018;66:317-318. 23) Madeleine MM, Finch JL, Lynch CF, et al. HPV-related cancers after solid organ transplantation in the United States. Am J Transplant 33) Monto AS, Ohmit SE, Petrie JG, et al. Comparative efficacy of in- 2013;13:3202–3209. activated and live attenuated influenza vaccines. N Engl J Med 2009;361:1260-1267. 24) Buchan CA, Kotton CN;AST Infectious Diseases Community of Practice. Travel medicine, transplant tourism, and the solid organ 34) Milligan R, Paul M, Richardson M, et al. Vaccines for preventing ty- transplant recipient—Guidelines from the American Society of phoid fever. Database Syst Rev 2018;5:CD001261.

68 | Clinical Liver Disease, VOL 15, NO 2, FEBRUARY 2020 An Official Learning Resource of AASLD