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Liver disease risk attributable to HCV, HIV, and HCV-HIV coinfection: an interaction analysis

William J Mcfarlane1,2, Jennifer A Flemming1,2,3, Jorge L Martinez-Cajas3

  • 1Department of Public Health Sciences, Queen's University.

AIDS (London, England)
|May 26, 2026
PubMed

Insights

Living with HIV significantly increases the risk of liver disease complications, particularly decompensation and hepatocellular carcinoma, when co-infected with hepatitis C virus (HCV). This interaction effect is synergistic, highlighting the need for integrated care for co-infected individuals.

Area of Science:

  • Hepatology and Infectious Diseases
  • Epidemiology and Public Health
  • Clinical Research

Background:

  • Hepatitis C virus (HCV) infection is a major cause of chronic liver disease.
  • Human Immunodeficiency Virus (HIV) infection can impact liver disease progression.
  • The combined effect of HCV and HIV on liver disease risk requires further elucidation in real-world settings.

Purpose of the Study:

  • To quantify the impact of living with HIV on the risk of liver disease outcomes in HCV-infected individuals.
  • To assess the interaction effect between HCV and HIV co-infection on the risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC).

Main Methods:

  • A large population-based cohort of 1,484,587 individuals in Ontario, Canada, was analyzed.
  • Data from 1999 to 2018 were used to track diagnoses of HCV, HIV, cirrhosis, decompensated cirrhosis, and HCC.
  • Time-dependent Cox regression and relative excess risk due to interaction (RERI) were employed to analyze risks and interaction effects.

Main Results:

  • Individuals with both HCV and HIV (HCV+/HIV+) exhibited the highest risk for cirrhosis, decompensation, and HCC compared to those without HCV.
  • A significant synergistic interaction effect was observed for the risk of decompensation (RERI = 1.2) and HCC (RERI = 2.3).
  • No significant interaction effect was found for the risk of cirrhosis (RERI = 0.9).

Conclusions:

  • This study provides the first population-based evidence of a synergistic additive interaction between HCV and HIV on the risk of liver decompensation and HCC.
  • The findings underscore the heightened risk of severe liver disease in individuals co-infected with HCV and HIV.
  • Integrated management strategies are crucial for mitigating liver disease progression in HCV/HIV co-infected populations.
Abstract

Keywords:
HIVcirrhosisdecompensationeffect modificationhepatitis Chepatocellular carcinomainteraction

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