Hepatitis B and Liver Transplantation

Overview

This lecture by Prof. Nancy Reau addresses the full spectrum of hepatitis B management — from screening and treatment indications to liver transplantation controversies and emerging curative therapies — with emphasis on closing the treatment gap and redefining cure.

Key Clinical Topics

• Hepatitis B care cascade: screening, diagnosis, and treatment gaps
• Serologic interpretation and phase classification of chronic hepatitis B
• Current treatment indications and guideline comparisons across major societies
• The "gray zone" and indeterminate phenotypes in hepatitis B
• Liver cancer surveillance updates and special populations
• Hepatitis B in the context of transplantation and reactivation risk
• Pipeline therapies and the quest for functional cure

Key Learning Points

• Elimination vs. cure: While hepatitis B is not classically curable, elimination — reducing transmission to negligible levels — is achievable through diagnostics, vaccination, and therapeutics
• Universal screening: CDC recommends the triple panel (surface antigen, surface antibody, core antibody total) for all individuals ≥18 years; vaccination recommended if all three are negative
• Pregnancy screening: Surface antigen-positive mothers require infant immunoglobulin and vaccine within 12 hours of birth; maternal treatment indicated for high viral load
• Serologic interpretation: Surface antigen positive = chronic infection; surface antibody = protection; isolated core antibody = resolved infection with reactivation risk under immunosuppression
• Treatment thresholds: Most guidelines align on treating when HBV DNA ≥2,000 IU/mL (AASLD: ≥20,000 IU/mL), elevated ALT, and surface antigen positivity; all guidelines recommend treatment in cirrhosis regardless of replication level
• Optimal treatment endpoint: Surface antigen loss is the ideal endpoint, associated with best long-term outcomes; current first-line agents (entecavir, tenofovir alafenamide [TAF], tenofovir disoproxil fumarate [TDF]) achieve surface antigen loss in <5% of patients
• Pegylated interferon: Finite course therapy; surface antigen loss achieved in only a minority of patients
• Gray zone indeterminate phenotype: Includes patients with elevated replication but near-normal ALT, or elevated ALT with low replication; shared decision-making and age-based thresholds guide treatment consideration
• Age-based treatment thresholds: SABA/APASL: age 30; EASL: age 35; AASLD: age 40 — treatment considered even without meeting traditional replication/ALT criteria
• Liver cancer surveillance post surface antigen loss: Men who lose surface antigen after age 40, and women after age 50, should continue surveillance
• HBV/HDV coinfection: Surveillance initiated at time of confirmed coinfection
• HBV/HIV coinfection: Liver cancer surveillance begins at age 18 in men and age 40 in women
• Terminology harmonization: Major societies including AASLD, EASL, APASL, and others are working to unify hepatitis B phase classification

Clinical Data & Study Results

• Global Hepatitis Report 2024: Of the millions infected with hepatitis B globally, very few are initiated on antiviral therapy, confirming a significant treatment gap
• HBV Research Network cohort: The most common gray zone phenotype is low replication with elevated ALT
• Fibrosis and age study: In patients with persistently normal ALT, those under age 35 had very low rates of significant fibrosis on histology; those aged ≥50 had >50% prevalence of concerning fibrosis, despite normal ALT throughout

Practical Takeaways

• Screen all adults ≥18 years with the full triple serologic panel; vaccinate those negative for all three markers
• Do not rely solely on ALT as a surrogate for hepatic inflammation in older patients with chronic hepatitis B — fibrosis risk is substantial even with normal enzymes
• Apply age-based thresholds (30–40 years) to initiate treatment conversations in gray zone patients, particularly those with developing fibrosis
• Engage in