Coinfection

AIDS 2012: HIV/HCV Coinfected People at Greater Risk for Liver Decompensation

Despite effective antiretroviral therapy (ART), people coinfected with HIV and hepatitis C remain at higher risk for decompensated liver disease and other liver-related complications than those with hepatitis C alone, according to findings presented this week at the XIX International AIDS Conference (AIDS 2012) in Washington, DC.

Prior studies have shown that HIV positive people with hepatitis C virus (HCV) coinfection have more rapid liver disease progression than HCV monoinfected individuals. Combination ART appears to slow liver disease progression, but late-stage clinical outcomes in the combination ART era are not fully understood.

Vincent Lo Re from the University of Pennsylvania and colleagues conducted a retrospective cohort study comparing 4280 ART-treated HIV/HCV coinfected patients and 6079 HCV monoinfected patients matched for age and race/ethnicity in the Veterans Aging Cohort Study Virtual Cohort during 1997-2010.

Almost all participants were men and about two-thirds were black. All had detectable HCV viral load and had not previously been treated for hepatitis C. Just over one-quarter were heavy alcohol drinkers. Co-infected people had been on combination ART for at least 1 year. About 45% had pre-ART CD4 T-cell counts of 200 cells/mm3 or less.

The researchers analyzed occurrence of clinical conditions related to liver decompensation including ascites (fluid accumulation in the abdomen), bacterial peritonitis (inflammation of the abdominal lining), and bleeding varices (swollen veins in the oesophagus). Hepatic encephalopathy and jaundice were not included.

They also looked at hepatocellular carcinoma and death from any cause. Follow-up continued for a median of 7 years for the coinfected group and 10 years for the monoinfected group.

Results

  • Coinfected people on combination ART had a significantly higher rate of liver decompensation than those with hepatitis C alone (6.3 vs 5.0%, respectively), for an adjusted hazard ratio (HR) of 1.83, or nearly twice the risk.
  • The median age at which decompensation occurred was similar for both groups.
  • At the time of the first decompensation episode, frequencies of both ascites and peritonitis were similar in the coinfected and monoinfected groups.
  • Bleeding varices, however, were about twice as common in the monoinfected group.
  • The 2 groups had similar rates of hepatocellular carcinoma (1.2% vs 0.9%, respectively), for an adjusted HR of 1.69.
  • Coinfected people had a small but statistically significant increase in risk for all severe liver events taken together.
  • Coinfected patients had significantly higher mortality than people with hepatitis C alone (32.9% vs 15.4%, respectively).
  • The coinfected group was less likely to have liver-related causes of death (7.8% vs 20.1% of all deaths, respectively), due to competing causes of death in the coinfected group.
  • Looking at coinfected people with low or undetectable HIV viral load, hazard ratios fell slightly (to 1.71 for < 1000 copies/mL and 1.73 for < 400 copies/mL), but rates of liver decompensation still remained higher in the coinfected group.
  • When stratifying by pre-ART CD4 cell count, hazard ratios were lower for people with 350-499 or 200-349 cells/mm3 than for those with < 200 cells/mm3.

"Despite ART, HIV/HCV [coinfected] patients had higher risk of hepatic decompensation that HCV mono-infected patients," the researchers concluded.

Lo Re suggested that poorer outcomes among HIV/HCV coinfected people may be related to greater immune activation, steatosis (fatty liver), or apoptosis (programmed cell death), with more study needed to determine the precise underlying mechanisms.

It is incumbent upon providers to assess risk factors, develop ways to detect the subgroups of patients at highest risk for rapid progression, and prioritize such individuals for hepatitis C treatment and trials of new agents, he added.

7/26/12

Reference

V Lo Re, J Tate, M Kallan, et al. Increased risk of hepatic decompensation and hepatocellular carcinoma in HIV/HCV-co-infected patients compared to HCV-mono-infected patients despite combination antiretroviral therapy. XIX International AIDS Conference. Washington, DC, July 22-27, 2012. Abstract WEAB0102.