Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort

Binu V John; Dustin Bastaich; Mahmoud Manouchehri Amoli; Robert J Wong; Donna M Evon; Shari S Rogal; David B Ross; Timothy R Morgan; Seth A Spector; Gabriel Villada; Hann-Hsiang Chao; Bassam Dahman; Veterans Analysis of Liver Disease (VALID) group of investigators

doi:10.1097/HEP.0000000000001092

Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort

Hepatology. 2024 Sep 10. doi: 10.1097/HEP.0000000000001092. Online ahead of print.

Affiliations

¹ Division of Gastroenterology and Hepatology, Miami VA Medical System, and Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL.
² Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA.
³ Division of Gastroenterology and Hepatology, Palo Alto VA Health System, and Division of Gastroenterology, Stanford University, Palo Alto, CA.
⁴ Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC.
⁵ Center for Health Equity Research and Promotion, Pittsburgh VA Health System, and Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA.
⁶ Division of Infectious Diseases, VA Washington DC Health Care, Washington D.C and George Washington University School of Medicine, Washington D.C.
⁷ Division of Gastroenterology and Hepatology, Long Beach VA Health System, and Division of Gastroenterology, University of California, Irvine, CA.
⁸ Department of Surgery, Miami VA Health System, and University of Miami Miller School of Medicine, Miami, FL.
⁹ Department of Pathology, Miami VA Medical System, Miami, FL.
¹⁰ Division of Radiation Oncology, Richmond VA Medical Center and Virginia Commonwealth University, Richmond, VA.

PMID: 39255517
DOI: 10.1097/HEP.0000000000001092

Abstract

Background: Hepatitis Delta Virus (HDV) infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a United States-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with hepatitis B virus (HBV). infection.

Methods: In a national cohort of 4,817 HBV infected veterans tested for HDV (99.6% US-born, 3.3% HDV positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of hepatocellular carcinoma (HCC), decompensation, and liver-related mortality (LRM), as well as all-cause mortality of patients with HDV compared to HBV mono-infection.

Results: HDV coinfection (vs. HBV monoinfection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p<0.001), and 10 years (19.14 vs. 10.18, p<0.001) respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by non-hepatic malignancies, (15.6 vs. 14.8%),cardiac (11.7 vs. 15.2%), and lung disease (5.2 vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (aHR 2.57, 95% CI 1.87-3.52, p<0.001), and all-cause mortality (aHR 1.52, 95% CI 1.20-1.93, p<0.001).

Conclusion: In a predominantly U.S born cohort of Veterans, HDV co-infection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV.