CROI 2015: End-Stage Liver Disease Among HIV+ People with Hepatitis B or C


People coinfected with HIV and hepatitis B or C virus are more likely to progress to end-stage liver disease, or liver failure, compared to those with HIV alone, and individuals triply infected with all 3 viruses are at greatest risk, according to study findings presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

Due to overlapping transmission routes, many people with HIV are also infected with 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 needing 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 therapy (ART), as fewer HIV-positive people are succumbing to opportunistic infections and other AIDS complications, liver disease has become a leading cause of morbidity and mortality for this population.

Marina Klein from McGill University 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 coinfection status.

This analysis included 34,119 HIV-positive adults participating in the 12 NA-ACCORD cohorts who were followed from January 1996 through December 2010. About 80% were men, just over 40% were white, and 35% were black. Nearly half were under age 40, about 35% were age 40-49, and about 13% were 50-59, with a small proportion being 60 or older. 14% had a history of injection drug use.

While only 3% had HBV coinfection, defined as a positive hepatitis B surface or e antigen (HBsAg or HBeAg) test or detectable HBV DNA, 11% had with HCV coinfection, defined as a positive antibody test or detectable HCV RNA.

About one-quarter had a CD4 T-cell count below 200 cells/mm3 and 21% had received a clinical AIDS diagnosis. Only 40% had used combination ART, reflecting the fact that older U.S. guidelines did not recommend treatment initiation until CD4 cells 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 esophagus or stomach), spontaneous bacterial peritonitis (internal infection) and hepatic encephalopathy (brain impairment due to buildup 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 129,000 person-years.
  • People who developed ESLD were older than those who did not and were more likely to have a history of injection drug use (29% vs 14%), a CD4 count <200 cells/mm3 (38%vs 26), and coinfection with HBV (11% vs 3%) or HCV (27% vs 11%).
  • Overall 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 3 time periods for any patient groups.
  • Overall, ESLD incidence rates were lowest among people with HIV alone, followed by HIV/HCV coinfection, then HIV/HBV coinfection, and highest for those with HIV/HBV/HCV triple infection (with the exception of HIV/HBV exceeding triple infection in the middle ART era):

o   Early ART era: 1.18, 6.04, 8.23, and 9.99 per 1000 person-years;

o   Middle ART era: 1.31, 5.62, 9.75, and 9.28 per 1000 person-years;

o   Late ART era: 1.26, 6.86, 7.50, and 16.97 per 1000 person-years.

  • Comparing the early vs modern ART eras, adjusted incidence rate ratios (IRRs) were 1.6 for people with HIV/HCV coinfection, 1.3 for those with HIV/HBV coinfection, and 0.6 for those with HIV/HBV/HCV.
  • Comparing the middle vs 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 3 time periods."

They noted that overall death rates were high during the early ART era, which may have lead 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.



MB Klein, KN Althoff, Y Jing, et al. Has Modern ART Reduced End-stage Liver Disease Risk in HIV-Hepatitis Coinfection? 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 638.