End-stage liver disease is a concern for people with HIV and hepatitis B or C co-infection

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People with HIV and hepatitis B or C virus co-infection are more likely to progress to end-stage liver disease (ESLD), or liver failure, than those with HIV alone, and individuals triply infected with all three viruses face the greatest risk, according to study findings presented at the recent Conference on Retroviruses and Opportunistic Infections (CROI 2015) in Seattle, USA.

Due to overlapping transmission routes, many people with HIV also have hepatitis B virus (HBV), hepatitis C virus (HCV) or both. Over years or decades, chronic hepatitis B or C can cause serious liver disease including cirrhosis, liver cancer, and potentially liver failure and the need for a liver transplant. In addition to viral hepatitis, other factors such as drug toxicity and heavy alcohol consumption can also contribute to serious liver damage.

Prior research has shown that HBV- and HCV-related liver disease progression is more rapid and possibly more severe in people with HIV. Since the advent of effective antiretroviral treatment (ART), as fewer people with HIV succumbed to opportunistic infections and other AIDS complications, liver disease has become a leading cause of morbidity and mortality in this population.


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.

end-stage disease

Final period or phase in the course of a disease leading to a person's death.

disease progression

The worsening of a disease.

Marina Klein of McGill University in Montreal and fellow investigators with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) estimated ESLD incidence since the introduction of combination ART according to HBV and HCV co-infection status.

This analysis included 34,119 adults with HIV participating in twelve NA-ACCORD cohorts who were followed from January 1996 to December 2010. About 80% were men, just over 40% were white and 35% were black. Nearly half were under 40, about 35% were aged 40 to 49 and about 13% were aged 50 to 59, with a small proportion being aged 60 or older; 14% had a history of injecting drugs.

Only 3% had HBV co-infection, defined as a positive hepatitis B surface or 'e' antigen (HBsAg or HBeAg) test or detectable HBV DNA, while 11% had HCV co-infection, defined as a positive HCV antibody test or detectable HCV RNA.

About one-quarter had a CD4 cell count below 200 cells/mm3 and 21% had received a clinical AIDS diagnosis. Just 40% had used combination ART, reflecting the fact that older US and Canadian guidelines did not recommend treatment initiation until the CD4 count fell below 350 cells/mm3.

The researchers looked at diagnoses of ESLD as indicated by liver failure complications including ascites (abdominal fluid accumulation), bleeding varices (enlarged veins in the oesophagus or stomach), spontaneous bacterial peritonitis (internal infection) and hepatic encephalopathy (brain impairment due to build-up of toxins), as well as liver cancer (hepatoma). ESLD rates were compared across the early (1996-2000), middle (2001-2005) and modern (2006-2010) ART eras. 

A total of 380 new ESLD events occurred over the 129,000 person-years of follow-up. People who developed ESLD were older than those who did not and were more likely to have a history of injecting drugs (29 vs 14%), a CD4 count <200 cells/mm3 (38 vs 26%) and to have HBV co-infection (11 vs 3%) or HCV co-infection (27 vs 11%).

ESLD incidence was similar in the early, middle and modern ART eras (3.08, 2.96 and 2.82 events per 1000 person-years, respectively). No significant changes in ESLD incidence rates were observed across the three time periods for any patient groups.

Overall, ESLD incidence rates were lowest among people with HIV alone, followed by HIV/HCV co-infection, then HIV/HBV co-infection, and highest for those with HIV/HBV/HCV triple infection (with the exception of HIV/HBV exceeding triple infection in the middle ART era. During the early ART era, ESLD rates were 1.18, 6.04, 8.23 and 9.99 per 1000 person-years, respectively. For the middle ART era, the corresponding rates were 1.31, 5.62, 9.75 and 9.28 per 1000 person-years, and for the late ART era, 1.26, 6.86, 7.50 and 16.97 per 1000 person-years.

Comparing the early versus modern ART eras, adjusted incidence rate ratios (IRRs) were 1.6 for people with HIV/HCV co-infection, 1.3 for those with HIV/HBV co-infection and 0.6 for those with HIV/HBV/HCV triple infection. Comparing the middle versus modern ART eras, adjusted IRRs were 1.1, 0.8 and 0.5, respectively.

"Hepatitis virus coinfected adults are at markedly increased risk for ESLD compared those infected with HIV alone, with triply infected patients at greatest risk," the researchers concluded. "No clear reduction in ESLD risk was observed over the three time periods."

They noted that overall death rates due to any cause were high during the early ART era, which may have led to an underestimate of ESLD risk for this period, but death rates were similar during the middle and modern ART eras. 

"The continued high incidence of ESLD despite modern ART underscores the urgent need to specifically address HCV and HBV infections in HIV-infected adults," they recommended.


Klein MB et al. Has modern ART reduced end-stage liver disease risk in HIV-hepatitis coinfection? 2015 Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, abstract 638, 2015.