Hepatitis delta-associated mortality in HIV/HBV-coinfected patients

Abstract

BACKGROUND AND AIMS Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. METHODS All HIV-infected patients with a positive HBsAg test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). RESULTS Of 818 patients with a positive HBsAg, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% confidence interval (CI): 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (PWID) (60.6% vs. 9.1%) and to have a positive HCV serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when PWID or HCV-coinfected patients were excluded from the analyses. CONCLUSIONS The prevalence of HDV in HBsAg-positive patients in the SHCS is high and HDV infection is independently associated with mortality and liver-related events, including HCC. LAY SUMMARY Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, 8 times more likely to die from a liver-related cause and 9 times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection