Hepatitis B: Update 2024 and Beyond

Hepatitis B: Update 2024 and Beyond — Comprehensive Lecture Summary

Speaker: Expert Speaker (Robert Gish, MD)

Format: CME/Medical Education Lecture

1. Main Clinical Topics Discussed

• Global epidemiology and burden of chronic hepatitis B (CHB)
• Diagnostic testing panels and correct interpretation of serological markers
• Disease phase classification and staging
• Barriers to treatment and linkage to care
• Emerging therapeutic pipeline targeting functional cure
• Patient-centered care, stigma, and quality of life
• Special populations: pregnancy, liver transplant, occult hepatitis B

2. Key Learning Points, Guidelines, and Recommendations

Epidemiology & Global Burden

• 257 million people globally are HBsAg-positive (Polaris Institute data)
• 2.4 million individuals estimated infected in the United States (Wong & Gish publication)
• >70% of global hepatitis B burden concentrated in Asia-Pacific and Africa
• ~1 million deaths per year attributable to hepatitis B; death rate unchanged over 20 years despite evolving guidelines

Testing Recommendations

• CDC recommends universal triple-panel testing for all adults in the United States
• WHO guidelines update anticipated imminently (to be announced at APASL meeting in Kyoto)
• Triple panel includes:

- HBsAg — if positive, indicates active infection

- HBcAb (core antibody) — indicates prior exposure; equates to presence of cccDNA

- HBsAb (surface antibody) — if positive with HBcAb negative, indicates vaccine-induced immunity

• Risk-based testing has failed across HIV, hepatitis C, and hepatitis B — universal testing is cost-effective (Tran & So, Stanford Liver Center)
• Every HBsAg-positive patient should receive hepatitis D (delta) antibody testing; estimated 15 million individuals with HDV globally, <5% diagnosed

Serological Interpretation Pearls

• HBcAb false positivity rate: 1 in 500 — core antibody positivity should be believed and acted upon, not dismissed
• HBsAg false positive possible in patients recently vaccinated (within days); test before vaccination when possible
• HBcAb-positive + HBsAg-negative = occult hepatitis B (OBI) — clinically significant, underdiagnosed
• "Immune tolerant" terminology is outdated — these patients are not immunologically tolerant (supported by viral immunology research)
• "Healthy carrier" is an oxymoron — no such entity in hepatitis B
• HBcAb positive + HBsAb positive = preferred term: "immune control"

Disease Classification (EASL-aligned terminology)

• Chronic infection (HBeAg-positive and HBeAg-negative subtypes)
• Chronic hepatitis (HBeAg-positive and HBeAg-negative subtypes)
• Reactivation
• Occult hepatitis B
• Phases defined by HBV DNA levels and ALT

Treatment Approach

• Currently <5% of individuals with hepatitis B have been treated globally
• Global trend moving toward treat-all strategies (Chinese guidelines cited as model)
• Eight documented clinical reasons to initiate treatment beyond DNA level and ALT alone
• HBV DNA remains a foundational test for risk stratification:

- Elevated DNA correlates with increased risk of cirrhosis and hepatocellular carcinoma (HCC)

• Guidelines historically have been overly complex (36-page documents) — cited as a primary barrier to care
• Speaker advocates for the "EASL Feline Guideline" — a simplified framework published in peer-reviewed literature

Liver Cancer Risk & Comorbidity Assessment

• HBV + metabolic dysfunction-associated steatotic liver disease (MASLD/NASH) markedly amplifies HCC risk
• Recommended one-time GAD score triple panel for HCC risk stratification
• Exact Sciences HCC risk assessment test available
• Family history of HCC and cirrhosis, alcohol use, and HbA1c should be routinely assessed
• Non-invasive staging preferred; liver biop