Prediction of Hepatocellular Carcinoma and Liver-related Events in Anti-hepatitis D Virus-positive Individuals

Clin Gastroenterol Hepatol. 2025 Oct;23(11):1964-1972.e4. doi: 10.1016/j.cgh.2024.08.036. Epub 2024 Oct 9.

Abstract

Background & aims: Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis, with a high risk of developing hepatocellular carcinoma (HCC) and liver-related mortality. Risk stratification is needed to guide HCC surveillance strategies and to prioritize treatment with antiviral agents.

Methods: We conducted a multicenter retrospective cohort of anti-hepatitis D virus (HDV)-positive individuals managed at sites in the Netherlands and the United Kingdom. We studied the 5-year cumulative incidences of HCC and liver-related events (first of HCC, liver transplantation, and liver-related mortality), in the overall cohort and among relevant subgroups.

Results: We analyzed 269 anti-HDV-positive individuals with a median follow-up of 4.3 years in which 47 first events occurred. The 5-year cumulative incidences of HCC and liver-related events were 3.8% and 15.6% in the overall cohort. The 5-year cumulative incidence of HCC and liver-related events for individuals without cirrhosis was 0% and 0.9% compared with 12% and 41.3% for individuals with cirrhosis (P < .001). The 5-year cumulative incidence of HCC and liver-related events was 0% and 2.1% among individuals with low PAGE-B scores, compared to 3.2% and 21.1% with intermediate and 25.4% and 45.5% with high-risk scores (P < .001). We found comparable results for the Fibrosis-4 score. Findings were consistent regardless of cirrhosis or detectable HDV RNA (P < .001).

Conclusions: Anti-HDV-positive individuals are at high risk of adverse liver-related outcomes. The incidence of HCC was negligible among individuals without cirrhosis and among individuals with low baseline PAGE-B and/or Fibrosis-4 scores. Therefore, these scores can be used to guide HCC surveillance strategies and potentially also for treatment prioritization.

Keywords: FIB-4; Hepatitis Delta; Hepatocellular Carcinoma; Liver-related Mortality; PAGE-B.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / epidemiology
  • Female
  • Hepatitis D, Chronic* / complications
  • Hepatitis Delta Virus
  • Humans
  • Incidence
  • Liver Cirrhosis / epidemiology
  • Liver Neoplasms* / epidemiology
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Retrospective Studies
  • Risk Assessment
  • United Kingdom / epidemiology