Decompensated liver disease more frequent in HIV/HCV co-infected people

Vincent Lo Re of the University of Pennsylvania. Image ©Liz Highleyman / hivandhepatitis.com
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Despite effective antiretroviral therapy, people co-infected 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 on Wednesday at the 19th International AIDS Conference (AIDS 2012) in Washington DC.

Prior studies have indicated that HIV positive people with hepatitis C virus (HCV) have more rapid liver disease progression than HCV-monoinfected individuals. Combination antiretroviral therapy (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 HIV/HCV ART-treated co-infected patients and 6079 HCV-monoinfected patients matched for age and race/ethnicity in the Veterans Aging Cohort Study Virtual Cohort between 1997 and 2010.

Glossary

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

disease progression

The worsening of a disease.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

abdomen

The part of the body below the chest, including the stomach, liver, intestines, kidneys, bladder, ovaries and uterus. The word ‘abdominal’ relates to pain or other problems in that area.

hepatic

To do with the liver.

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 one year. About 45% had pre-ART CD4 cell counts of 200 cells/mm3 or less.

The researchers analysed 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 seven years for the co-infected group and ten years for the monoinfected group.

Co-infected 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, however.

At the time of the first decompensation episode, frequencies of both ascites and peritonitis were similar in the co-infected and monoinfected groups, but bleeding varices were about twice as common in the monoinfected group.

The two groups had similar rates of hepatocellular carcinoma (1.2 vs 0.9%, respectively), for an adjusted HR of 1.69. Co-infected people had a small but statistically significant increase in risk for all severe liver events taken together.

Co-infected people had significantly higher mortality than people with hepatitis C alone (32.9 vs 15.4%, respectively). The co-infected 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 co-infected group.

Looking at co-infected people with low or undetectable HIV viral load, hazard ratios fell slightly (to 1.71 for <1,000 copies/mL and 1.73 for <400 copies/mL), but rates of liver decompensation still remained higher in co-infected compared with mono-infected patients.

Lo Re explained that when stratifying according to pre-ART CD4 cell count, hazard ratios were lower for people with 350-499 or 200-349 cells/mm3 than for those with less than 200 cells/mm3.

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

Lo Re suggested that poorer outcomes among HIV/HCV co-infected people may be related to greater immune activation, steatosis (fatty liver) or apoptosis (programmed cell death), with more study needed to determine the precise 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 to prioritise such individuals for hepatitis C treatment and trials of new agents, he added.

References

Lo Re V 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. 19th International AIDS Conference, abstract WEAB0102, Washington, DC, 2012.

View the abstract on the conference website.

View the slides from the presentation on the conference website.