HIV/HCV coinfected patients more prone to end-stage liver disease without treatment

Individuals coinfected with HIV and hepatitis C virus are more likely to develop end-stage liver disease (ESLD) compared to patients with hepatitis C virus, alone, according to a study presented at the Sixteenth International AIDS Conference in Toronto on August 15^th. However, the investigators found that coinfected patients who achieved a sustained response to hepatitis C therapy were no more likely to progress to end-stage liver disease than their hepatitis C monoinfected peers.

Most studies show that coinfected individuals experience more rapid liver fibrosis progression than those with hepatitis C alone, although this may be less likely if they have well-controlled HIV. Coinfected patients are also less likely to respond to interferon-based therapy.

Firouzé Bani-Sadr from INSERM presented data from a study of liver disease progression among co-infected patients in France. The researchers prospectively followed 248 HIV and hepatitis C coinfected participants who received pegylated or conventional interferon, both with ribavirin, for 48 weeks in the RIBAVIC trial. Overall, 29% achieved sustained virological response, or continued undetectable hepatitis C viral load, 24 weeks after the completion of therapy.

The average age of the patients was 42 years, 75% were men, and 59% had hard-to-treat hepatitis C genotypes 1 or 4. Most (81%) were taking potent anti-HIV therapy, about half had HIV viral loads below 200 copies/mL, and the average CD4 cell count was 567 cells/mm³. At the start of the study, 35% already had severe liver fibrosis or cirrhosis.

After an average follow-up period of 33 months, 17 events indicative of end-stage liver disease occurred in nine patients (4%). These events included liver decompensation (with symptoms such as severely elevated bilirubin, ascites, hepatic encephalopathy, or bleeding esophageal varices), hepatocellular carcinoma, need for liver transplant, and liver-related death. Six patients died of liver-related causes and two of other causes.

All cases of end-stage liver disease occurred in patients who did not achieve sustained response to hepatitis C treatment, and all but one occurred in individuals who had advanced fibrosis at the start of the study. End-stage liver disease did not occur in patients with severe fibrosis who permanently cleared hepatitis C with treatment. Among non-responders, end-stage liver disease was more common among patients with advanced fibrosis who also had lower CD4 cell counts.

In a stratified analysis, the only independent risk factors for end-stage liver disease were cirrhosis or severe fibrosis at the start of the study (p3 (p=0.022), and lack of sustained virological response to anti-hepatitis C therapy (p=0.068).

In conclusion, the researchers stated, “Our study confirms that the rate of spontaneous hepatic decompensation in coinfected patients with asymptomatic cirrhosis is higher (7.4% per year) than in hepatitis C monoinfected patients (3-4% per year).”

They recommended that, “clinicians should consider the evidence that sustained virological response seems associated with a reduction in long-term morbidity and mortality related to hepatitis C” when discussing treatment options with patients.