Improved HIV Treatment Has Not Reduced End-Stage Liver Disease in HIV/HCV Coinfected People


Incidence of end-stage liver disease (ESLD) among HIV-positive people with viral hepatitis changed little between 1996 and 2010, despite major improvements in HIV treatment and care, investigators from Canada and the U.S. report in the November 1 edition of Clinical Infectious Diseases

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"This study is the largest and longest prospective evaluation of validated ESLD outcomes conducted in an HIV-infected population," Marina Klein from McGill University and colleagues wrote. "ESLD events were common in all time periods studied and occurred more frequently among those with viral hepatitis coinfection."

Over 36,000 people were included in this analysis. There was little evidence that the major advances in HIV therapy that occurred during the study period had a meaningful impact on incidence of ESLD, which remained high among people with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) coinfection. Even in the modern antiretroviral era (2006-2010), over a third of people with HBV infection were not taking tenofovir -- a drug active against both HIV and HBV -- and just 1% of individuals with HCV received therapy for this infection.

End-stage liver disease in this study refers to liver failure leading to liver transplantation, or laboratory and clinical evidence of severe fibrosis, or a clinical event indicating decompensated cirrhosis such as ascites, bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, or hepatocellular carcinoma.

Around 1 in 5 people living with HIV have HCV coinfection and between 5% and 15% have HBV coinfection. Liver disease is a leading cause of serious illness and death in these people.

Antiretroviral therapy (ART) for HIV has improved dramatically since it was first introduced in 1996, resulting in higher life expectancy and a steep reduction in illness and death, but it is unclear if these gains in HIV treatment have been accompanied by a fall in rates of ESLD, especially among people with viral hepatitis coinfection.

Investigators from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) therefore designed a prospective observational study to see if incidence of ESLD as validated by physicians changed according to antiretroviral era -- early (1996-2000), middle (2001-2005), and modern (2006-2010) -- and by viral hepatitis coinfection status. Results were adjusted to take into account hepatitis status, age, sex, race, cohort, CD4 count, and HIV viral load.

Adults in 12 cohorts were included in the analysis, the study population comprising a total of 34,119 individuals. Overall, 19% had HCV coinfection, 5% had HBV coinfection, and 2% had triple infection (HIV/HBV/HCV). Individuals were followed for a median of 2.9 years and contributed 129,818 person-years of follow-up.

During this time there were 380 incident ESLD events, for an incidence ratio of 2.9 per 1000 person-years.

People developing ESLD were older, more likely to be male, more often white, had a history of injection drug use, had HBV and/or HCV coinfection, had evidence of liver dysfunction or fibrosis at baseline, and had a low CD4 count and detectable viral load.

Overall, the proportion of people developing ESLD did not vary by calendar period or hepatitis status.

The highest incidence of ESLD was observed among people with triple infection (11.57 per 1000 person-years), followed by HIV/HBV coinfection (9.72 per 1000 person-years), HIV/HCV coinfection (6.10 per 1000 person-years), and HIV monoinfection (1.27 per 1000 person-years). The authors suggest that ESLD in people with HIV monoinfection was probably due to heavy alcohol use or the side effects of older antiretroviral drugs.

Comparison between the early and modern antiretroviral eras showed that there was little if any evidence of a change in adjusted incidence rate ratios (IRR) of ESLD among people with viral hepatitis: HCV 0.95, HBV 0.95, and triple infection  1.52.

Increasing rates of HIV suppression were observed over the study period, reaching 85% in the modern treatment era, with no difference in suppression rates according to viral hepatitis status.

Could the continuing high rates of ESLD be explained by sub-optimal hepatitis care? There was some evidence to suggest this could be the case. Only 1% of people with HCV infection received treatment for this infection, and in the modern antiretroviral era, 35% of people with HBV infection were not receiving tenofovir.

"HIV infected patients coinfected with HBV or HCV are at markedly increased risk of ESLD compared with those infected with HIV alone," concluded the investigators. "The continued high incidence of ESLD despite modern ART underscores the urgent need to specifically address HCV and HBV infections in HIV-infected adults. Improved identification, staging, monitoring and treatment of co-infected persons should be prioritized."

In an accompanying editorial Linda Wittkop from the University of Bordeaux called for further studies to investigate the impact of new HCV therapies on ESLD events in people with HIV/HCV coinfection, adding "a close follow-up on the effect of combination ART including drugs active against both HIV and HBV in HBV/HIV coinfected patients is needed to confirm a reduced risk of hepatic decompensation in these patients."



MB Klein, KN Althoff, Y Jing, et al. Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras. Clinical Infectious Diseases 63(9):1160-1167. November 1, 2016.

L Wittkop. End-Stage Liver Disease in HIV Infection: An Avoidable Burden? (Editorial Commentary). Clinical Infectious Diseases 63(9):1168-1170. November 1, 2016.