Hepatitis Delta Is a Major Determinant of Liver Decompensation Events and Death in HIV-Infected Patients

Background. Coinfection with hepatitis viruses is common in individuals infected with human immunodefi-ciency virus (HIV) and has become a leadingcause ofcomplications and death in those receiving antiretroviral ther-apy (ART).Methods. We retrospectively examined the effect of coinfection with hepatitis B, C, and/or D viruses (HBV,HCV, HDV, respectively) on liver decompensation events (ascites, variceal bleeding, encephalopathy, and/or hepa-tocellularcarcinoma) and liver-related mortalityin HIV-positivepatients on regular follow-up since theyear 2004 ata reference HIV clinic in Madrid, Spain.Results. A total of 1147 HIV-infected patients (mean age, 42 years; 81% males; 46% intravenous drug users,85.4% on ART) were analyzed. Mean follow-up was 81.2±17.8 months. At baseline, 521 patients (45.4%) wereHCV-antibody positive, 85 (7.4%) were hepatitis B surface antigen positive, and 17 (1.5%) were anti-HDV positive.A total of 233 HIV/HCV-coinfected patients received antiviral therapy for HCV, of whom 106 (45%) achieved sus-tained virologic response (SVR). Overall, 15 patients died of liver-related complications and 26 developed hepaticdecompensation events. Taking as controls the 524 HIV-monoinfected patients, HDV coinfection (adjusted hazardratio [AHR], 7.5; 95% confidence interval [CI], 1.84–30.8; P=.005) and baseline liver stiffness (AHR, 1.1; 95% CI,1.07–1.13; P<.0001) were associated with a higher rate of liver-related morbidity and mortality. In contrast, SVRfollowing hepatitis C therapy in HIV/HCV-coinfected patients was protective (AHR, 0.11; 95% CI, .01–.86; P=.03).Conclusions. Hepatitis delta is associated with a high rate of death and liver decompensation events in HIV-infected patients on ART.Keywords. HIV; hepatitis (HBV, HCV, and HDV); cirrhosis; death.Hepatitisdeltavirus(HDV) wasfirstdiscoveredin1977[1].HDVisthesmallesthumanRNAviruswithasingle-stranded negative sense genome of approximately 1700nucleotides forming a covalently closed circle [2]. TheRNA encodes a protein called the delta antigen,which is subsequently encased in an envelope embed-ded with the hepatitis B surface antigen (HBsAg).HDV replication only takes place in the presence ofHBV infection. Hepatitis delta causes the most severeform of viral hepatitis in humans, including fulminantliver failure, rapid progression to cirrhosis and hepaticdecompensation, and increased risk of hepatocellularcarcinoma (HCC) [3,4].Because shared routes oftransmission, infectionwithhepatitis viruses B, C, and D (HBV, HCV, and HDV,respectively) is common in individuals infected withhumanimmunodeficiencyvirus(HIV)[5].Notsurpris-ingly, the success and wide use of antiretroviral therapyhas unveiled liver disease as a major cause of clinicalcomplications and death in HIV-positive individualscoinfectedwithhepatitisviruses[6].Effortstominimizethe impact of hepatitis B and C using antiviral therapy