Viral Hepatitis
Publication Date: April 1, 2019
Last Updated: March 14, 2022
Recommendations
HEPATITIS B AND D VIRUSES
Diagnostic strategies
LT candidates with HBV infection who are at high risk for HDV should be screened for concomitant HDV infection. (Low, Strong)
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Recipients who receive a LT for HBV should be monitored with HBsAg and HBV DNA every 3 months within the first year after LT, and every 6 months thereafter, regardless of prophylactic or therapeutic regimen. (Low, Strong)
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Co‐infected recipients who receive a LT for HBV/HDV should be monitored with HDV DNA every 3 months within the first year after LT, and every 6 months thereafter. (Low, Strong)
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LT recipients with HBV infection who have low or undetectable HBV DNA but have elevated ALT should be evaluated for HDV co‐infection. (Low, Strong)
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Treatment
All LT candidates with HBV infection with any detectable HBV DNA should be treated with an NA (ETV, TDF, or TAF0. (High, Strong)
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Decompensated patients should be closely monitored for adverse effects such as renal dysfunction or lactic acidosis during nucleos(t)ide analogues (NA) therapy. (Low, Strong)
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Recurrent HBV should be managed with a NA (ETV, TDF, or TAF), and a test for drug resistance should be obtained. The choice of NA should be carefully based on the resistance profile. (Low, Strong)
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Recurrent HDV should be managed through long‐term HBV suppression of HBV DNA and cautious use of pegylated interferon alpha with very close monitoring of graft function. (Low, Strong)
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Prevention
Administration of ETV, TDF, or TAF, with or without short‐term HBIg, is recommended after LT for prevention of HBV recurrence in recipients who are HBsAg positive, regardless of HBV DNA level or HBeAg status at time of LT. (Moderate, Strong)
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Recipients who are co‐infected with HIV or HDV may warrant longer‐term HBIg (one year or longer) in addition to indefinite NA therapy to prevent HBV recurrence. (Low, Weak)
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HBsAg‐negative recipients who receive livers from HBcAb‐positive donors are at risk for HBV transmission and should receive long‐term NA prophylaxis. (Moderate, Strong)
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Non‐HBV‐infected LT candidates or recipients who are not immune to HBV, including those with isolated HBcAb positivity, should be vaccinated. Patients with advanced cirrhosis, on immunosuppression, or non‐responders to previous vaccination should be given a double‐dose regimen (40 μg) of hepatitis B vaccine at standard intervals. (Low, Strong)
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Non-hepatic transplantation
Diagnosis
Initial screening for HBV should be done at the time of transplant candidate assessment and include HBsAg, anti‐HBs, and anti‐HBc. (Moderate, Strong)
Non‐immune candidates should be vaccinated.
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HBsAg‐positive non‐hepatic SOT candidates should undergo additional testing, including HBeAg, anti‐HBe, quantitative HBV DNA, liver enzymes, and a baseline abdominal ultrasound according to standard guidelines. (Moderate, Strong)
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HBsAg‐positive non‐hepatic SOT candidates and recipients at risk should undergo surveillance for HCC, according to published guidelines in the non‐transplant population, with an abdominal ultrasound with or without alpha‐fetoprotein every 6 months. (Low, Strong)
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Treatment
Non‐hepatic SOT candidates with chronic HBV should be evaluated for the need for therapy by a specialist with expertise in HBV management prior to transplantation. (Low, Strong)
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If treatment for HBV is indicated, TDF, TAF, or ETV is preferred due to their potency and high barriers to resistance; in those with renal dysfunction, ETV or TAF is preferred. (Moderate, Strong)
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If treatment for HBV is initiated, monitoring on treatment should be in accordance with guidelines in the general population.
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Once therapy is started, it should be continued indefinitely pre‐ and post‐transplant. (Moderate, Strong)
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Prevention/Prophylaxis
All HBV‐uninfected, non‐immune, SOT candidates should be vaccinated for HBV as early in the course of their disease as possible. (Moderate, Strong)
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HBIg is not recommended in the prevention of HBV peri‐transplant in non‐hepatic recipients. (Moderate, Strong)
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Due to the high risk of reactivation, non‐hepatic SOT recipients with chronic HBV (ie, HBsAg positive) who did not require antiviral therapy prior to transplant should be initiated on potent NA therapy at the time of transplant and be continued indefinitely post‐transplant. This is independent of the HBV DNA levels. (High, Strong)
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ETV or TDF is recommended as first‐line therapy. (Moderate, Strong)
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Follow‐up monitoring should follow guidelines in the general population and include liver enzymes and HBV DNA every 3‐6 months as well as hepatocellular carcinoma surveillance, in those meeting criteria, with ultrasound every 6 months. (Low, Strong)
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In those with markers of past HBV infection (HBsAg negative, anti‐HBc positive ± anti‐HBs positive), routine antiviral prophylaxis is not recommended, but may be considered in those felt to be at increased risk of reactivation (eg, anti‐HBc + alone, detectable HBV DNA, or intense immunosuppression). (Low, Weak)
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For those not receiving prophylaxis, monitoring should be considered with HBV DNA and HBsAg every 3‐6 months for at least the first year after transplant and later during periods of more intense immunosuppression. (Low, Weak)
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Organs from HBsAg‐positive donors may be considered with use of HBIg/antiviral prophylaxis on individual case basis, weighing the risks and benefits, and informed consent. (Low, Weak)
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In HBV immune (anti‐HBs positive) recipients of an anti‐HBc‐positive non‐hepatic organ, no prophylaxis is needed. (Moderate, Strong)
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For HBV non‐immune recipients of an anti‐HBc‐positive non‐hepatic organ antiviral prophylaxis with LAM should be considered for up to 1 year post‐transplant. (Low, Weak)
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Recipients of organs from HBsAg‐ or anti‐HBc‐positive donors should undergo monitoring with liver enzymes, HBsAg, and HBV DNA at least every 3 months for at least 12 months post‐transplant, (Low, Weak)
with subsequent management based on evolution of test results over the first year.
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HEPATITIS C VIRUS
Diagnostic strategies
HCV RNA is the marker of HCV viremia from HCV recurrence or de novo HCV infection from LT and is detectable within a week from LT. (Moderate, Strong)
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Liver biopsies remain the gold standard for diagnosing histologic HCV recurrence. (Moderate, Strong)
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Non‐invasive assessments for fibrosis such as transient elastography can be used to monitor fibrosis progression when indicated, particularly in those who do not respond to therapy or have advanced fibrosis at the time of viral eradication. (Moderate, Strong)
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Treatment
LT candidates with decompensated cirrhosis with MELD scores ≤20 with no other indication for LT should be considered for therapy, as they have a higher chance for clinical improvement that could result in delisting. (Moderate, Weak)
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LT candidates with decompensated cirrhosis with MELD scores 21‐27 should be considered for therapy, with the decision to treat individualized to the potential reversibility of the candidate's indication for LT, anticipated wait time, access to a donor organ (including HCV‐infected donors), and comorbidities that may impact treatment tolerability or efficacy. (Low, Weak)
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Patients with a non‐MELD score indication for LT such as HCC, or have a MELD score >27, may be considered for treatment before LT or treatment may be deferred after LT to keep the donor pool open to HCV NAT‐positive donors and to achieve better SVR rates after LT. (Low, Weak)
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Recurrent HCV should be treated once the patient is clinically stable (usually after the first few weeks following LT), even before any laboratory or histologic evidence of hepatitis emerges. (High, Strong)
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The choice of DAA therapy must include consideration of drugdrug interactions with immunosuppressive agents. (High, Strong)
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Unexplained elevations in liver enzymes during or after DAA therapy should prompt for an investigation for possible immune‐ mediated graft dysfunction. (Low, Strong)
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Candidates and recipients should be screened for current or past HBV infection before DAA therapy is started. Monitoring for HBV reactivation should be done during therapy until SVR12 is achieved. (Moderate, Strong)
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Prevention
The most effective prevention for hepatitis C recurrence is viral eradication before LT. However, the decision to treat LT candidates should be individualized to the candidate's indication for LT (whether HCC is an indication or not), access to a donor organ (including HCV‐infected donors), and comorbidities that may impact treatment safety and efficacy. (High, Strong)
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Candidates who receive a LT while in the midst of DAA therapy should continue treatment for four weeks following LT to prevent HCV recurrence. (Low, Weak)
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Prevention of transmission from infected liver transplant candidates or recipients is best achieved with viral eradication in the infected individual. (High, Strong)
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Non-hepatic transplantation
Diagnosis
Screening for antibody to HCV should be done at the time of transplant candidacy assessment, with HCV RNA used to confirm current infection. (Low, Strong)
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Hepatic fibrosis assessment by liver biopsy or non‐invasive methods is recommended in the assessment of all non‐hepatic SOT candidates with chronic HCV to guide optimal management and timing of therapy. (Moderate, Strong)
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Treatment
All non‐hepatic transplant recipients with chronic HCV should be considered for treatment. (Moderate, Strong)
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For those with genotype 1 or 4 infection, options for therapy include glecaprevir/pibrentasvir for 12 weeks or sofosbuvir/ledipasvir for 12 weeks. (Moderate, Strong)
In those with eGFR <30, SOF‐based regimens are currently not indicated.
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- with daclatasvir plus sofosbuvir plus ribavirin considered and alternative.
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For those with genotype 2, 3, 5, or 6 infection, glecaprevir/pibrentasvir for 12 weeks is recommended, (Moderate, Strong)
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Prevention/Prophylaxis
Recommendations on the timing of therapy, before or after transplant, need to be individualized and consider the expected wait time, availability of HCV viremic donor as well as the severity of liver disease in the individual candidate. (Low, Strong)
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HCV positive Donors
HCV Ab‐positive, RNA‐negative donors can be safely utilized. (Moderate, Strong)
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Given the possibility of eclipse phase reinfection or false negative HCV RNA, recipients of HCV Ab‐positive RNA‐negative organs should undergo follow‐up testing with HCV RNA at 1‐3 months post‐transplant. (Low, Strong)
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HCV viremic donors may be considered for HCV‐negative recipients in the setting of a clinical trial or structured clinical protocol, with informed consent and an established plan to treat post-transplant, including knowledge of DAA reimbursement policies of recipient's insurance. HCV antiviral therapy may either be preemptive at transplant or early post‐transplant at the detection of HCV viremia in the recipient. (Moderate, Strong)
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HEPATITIS E VIRUS
Diagnostic strategies
The diagnosis of hepatitis E infection in transplant recipients should be made with HEV RNA testing of the serum and/or stool, as serologic assays can be unreliable in this population. (High, Strong)
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While a liver biopsy may be supportive of the diagnosis, the histologic findings are often nonspecific. (Low, Strong)
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Liver biopsies, however, would be useful in assessing the severity of fibrosis and for progression of the disease. (Moderate, Strong)
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Unexplained chronic hepatitis on liver biopsies should prompt a search for HEV infection in transplant recipients. (Moderate, Strong)
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Treatment
Reduction of immunosuppression is the first‐line intervention for chronic HEV infection. (Moderate, Strong)
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If reduction in immunosuppression does not clear the HEV virus, RBV monotherapy for at least 3 months is the treatment of choice. (Low, Strong)
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Patients who relapse after a 3‐month course of RBV should be treated for a longer duration of 6‐9 months. (Low, Weak)
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Pegylated interferon alpha can be considered as an alternative therapy for chronic HEV if RBV is not tolerated or a prolonged RBV course fails to eradicate the virus. (Low, Weak)
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Prevention
Prevention of chronic HEV requires following good food and general hygiene practices. (Moderate, Strong)
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Recommendation Grading
Overview
Title
Viral Hepatitis
Authoring Organization
American Society of Transplantation
Publication Month/Year
April 1, 2019
Last Updated Month/Year
March 16, 2023
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of viral hepatitis in the pre‐ and post‐transplant period.
Target Patient Population
Pre-/Post-transplant recipients
Inclusion Criteria
Female, Male, Adolescent, Adult, Older adult
Health Care Settings
Ambulatory, Hospital, Operating and recovery room, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Prevention, Management
Diseases/Conditions (MeSH)
D014180 - Transplantation, D019737 - Transplants, D000998 - Antiviral Agents, D006505 - Hepatitis, D006518 - Hepatitis Viruses
Keywords
antiviral, infection, transplant, solid organ transplant, hepatitis
Source Citation
Te, H, Doucette, K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant. 2019; 33:e13514.