Antiretroviral therapy - but not treatment for chronic hepatitis C virus (HCV) infection - was associated with significantly improved survival in HIV/HCV co-infected individuals with liver cirrhosis, researchers reported on February 10th at the Sixteenth Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal, Canada.
Maria Luisa Montes from Hospital Universitario La Paz in Madrid, Spain, presented findings from a prospective multicentre study looking at the effect of hepatitis C treatment in HIV/HCV co-infected patients with compensated cirrhosis or advanced fibrosis.
Compensated cirrhosis means that even though the liver has been heavily scarred, it is still able to perform most of its normal functions. Chronic hepatitis C is responsible for more than 90% of cirrhosis cases in HIV-positive people, the researchers noted.
A total of 248 co-infected participants were assessed to determine factors associated with survival and time to a first episode of liver decompensation, and in particular whether hepatitis C treatment improved the prognosis of patients with compensated cirrhosis.
The investigators used an expanded definition of survival that included development of liver cancer and liver transplantation in addition to death.
Liver decompensation included bleeding in the oesophagus or stomach, abdominal fluid accumulation (ascites), brain damage (encephalopathy), spontaneous bacterial infection of the abdominal lining (peritonitis) and kidney failure (hepatorenal syndrome).
The factors the investigators included in their analysis were current and nadir (lowest-ever) CD4 cell count, HIV viral load, type of antiretroviral therapy, HCV genotype, whether patients had received hepatitis C treatment and whether they achieved sustained virological response (continued undetectable HCV viral load 24 weeks after completing treatment), concurrent chronic hepatitis B, and Child-Pugh score (a measure of liver disease prognosis).
More than three-quarters (78%) of the study participants were men and the median age was 42 years. Most had a history of injecting drug use. Overall, they had well-controlled HIV disease, with 88% taking combination antiretroviral therapy at baseline, 60% receiving continuous antiretroviral treatment without interruptions for the duration of the study, and 60% with undetectable HIV viral load; the median CD4 cell count was 437 cells/mm3.
With regard to liver disease, participants had been infected with HCV for 23 years on average and had cirrhosis or advanced bridging fibrosis, diagnosed for one year on average. About three-quarters had the harder to treat HCV genotypes 1 and 4. In addition, 27% were heavy alcohol drinkers and 4% also had chronic hepatitis B.
About three-quarters were currently taking or had received treatment for hepatitis C - mostly using the standard of care regimen of pegylated interferon plus ribavirin - and the sustained virological response rate was 24%, leaving 74% as relapsers or non-responders (1% were still undergoing treatment).
During a median 34 months of follow-up, a total of 30 endpoints were recorded: 25 deaths, 2 cases of liver cancer and 5 liver transplants. In addition, 28 patients experienced a first episode of liver decompensation, most often ascites.
The overall survival rate for co-infected patients with compensated cirrhosis was 85% at three years. In a univariate analysis, participants treated for hepatitis C were significantly more likely than untreated patients to survive during the follow-up period (91% vs 71% at three years), but the difference between sustained responders and non-responders was not significant (95% vs 90% at three years).
Hepatitis C treatment did not increase the time to a first episode of decompensation, nor did sustained response compared with non-response.
In a multivariate analysis controlling for potential confounding factors, only a baseline Child-Pugh score of 'B' or 'C' (indicating 81% and 45% probability of one-year survival, respectively) and non-continuous use of antiretroviral therapy were significantly associated with first liver decompensation and decreased survival, whilst decompensation during follow-up also predicted death, liver cancer or transplantation.
Although treatment of chronic hepatitis C was significantly associated with increased survival over three years in the univariate analysis, the investigators noted, this association disappeared after controlling for other factors.
“Continuous antiretroviral therapy and Child-Pugh scores are more important prognostic factors than anti-hepatitis C treatment”, they concluded.
They added the caveat that this study does not rule out a possible survival benefit of sustained response to hepatitis C treatment due to the low number of participants, and said longer follow-up might be needed to see an effect.
Because the success rate of hepatitis C treatment in co-infected individuals with liver cirrhosis is low, the researchers recommended that "every effort should be made to avoid progression to cirrhosis" in HIV/HCV co-infected patients - an argument for timely HCV screening, regular monitoring of liver health and prompt treatment when indicated.
Montes ML et al. Survival of HIV/HCV-co-infected patients with compensated liver cirrhosis: effect of HCV therapy. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 106, 2009.