Improvements in HIV treatment and care have had no impact on rates of endstage liver disease among HIV-positive people with viral hepatitis

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Incidence of endstage 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 United States report in the online edition of Clinical Infectious Diseases

Over 36,000 people were included in the 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) co-infection. Even in the modern antiretroviral era (2006-2010), over a third of people with HBV infection were not taking tenofovir – a drug potent against both HIV and HBV – and just 1% of individuals with HCV infection received therapy against this infection.

“This study is the largest and longest prospective evaluation of validated ESLD outcomes conducted in an HIV-infected population,” write the investigators. “ESLD events were common in all time periods studied and occurred more frequently among those with viral hepatitis co-infection.”


hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

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

Around one in five people living with HIV have HCV co-infection and between 5 and 15% have HBV co-infection. Liver disease is a leading cause of serious illness and death in these people.

HIV therapy has improved dramatically since it was first introduced in 1996, resulting in greatly improved life expectancy and a steep reduction in illness and death, but it is unclear if these gains in antiretroviral treatment have been accompanied by a fall in rates of ESLD, especially among people with viral hepatitis co-infection.

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 co-infection status. Results were adjusted to take account of 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 34,119 individuals. Overall, 19% had HCV co-infection, 5% had HBV 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, an incidence ratio of 2.9 per 1000 person-years.

People developing ESLD were older, more likely to be male, white, had a history of injecting drug use, had co-infection with HCV and/or HBV, had evidence of liver dysfunction or fibrosis at baseline, a low CD4 count and a 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 HBV (9.72 per 1000 person-years), HCV (6.10 per 1000 person-years) and HIV mono-infection (1.27 per 1000 person-years). The authors suggest that ESLD in people with mono-infection was probably due to alcohol abuse and/or the side-effects of older anti-HIV drugs.

Comparison between the early and modern antiretroviral eras showed there was little if any evidence in a change of adjusted incidence rate ratios (aIRR) of ESLD among people with viral hepatitis: HCV = 0.95, 95% CI, 0.61-1.47; HBV = 0.95, 95% CI, 0.40-2.26; triple infection = 1.52, 95% CI, 0.46-5.02.

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 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 against this infection, and in the modern antiretroviral era, 35% of people with HBV infection were not receiving tenofovir.

“HIV infected patients co-infected with HBV or HCV are at markedly increased risk of ESLD compared with those infected with HIV alone,” conclude 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.”

The author of an accompanying editorial calls for further studies to investigate the impact of new HCV therapies on ESLD events in people with HIV/HCV co-infection, adding “a close follow-up on the effect of cART including drugs active against both HIV and HBV in HBV/HIV co-infected patients is needed to confirm a reduced risk of hepatic decompensation in these patients.”


Klein MB et al. Risk of endstage liver disease in HIV-viral hepatitis co-infected persons in North America from the early to modern antiretroviral therapy eras. Clin Infect Dis, online edition, 2016.

Wittkop L. Endstage liver disease in HIV infection: an avoidable burden? Clin Infect Dis, online edition, 2016.