Decreased Prevalence of Steatosis after Treatment for Chronic Hepatitis C in HIV-HCV Coinfected Subjects

By Marina Nunez, MD

Factors associated with hepatic steatosis in HIV/HCV-coinfected patients concerning its influence on response to treatment are not clear. Using the database of a large trial of anti-HCV therapy performed in HIV/HCV-coinfected patients (APRICOT), the factors associated with steatosis, the impact of steatosis on response to therapy, as well as its outcome after treatment were evaluated [1,2].

In that study, pegylated interferon (pegIFN)-a-2a (Pegasys) combined with ribavirin (RBV) was compared to pegIFN-a-2a monotherapy and to standard IFN with RBV. Steatosis was diagnosed by biopsy, and defined as >5% of hepatocytes with fatty changes per low power field. The patients included in this analysis had both pre- and post-treatment biopsies.

Out of the 283 patients included in the analysis, 65 (23%) had steatosis at baseline, with similar prevalence across groups. There were no differences regarding the use of antiretroviral therapy either.

Factors found to be independently associated with steatosis in the multivariate analysis include HCV genotype 3 (OR 5.54, 95% CI 2.76-11.09; p<0.0001), advanced stages of liver fibrosis (OR 2.31, 95% CI 1.06-5.06; p=0.036), and increased serum levels of glucose (OR 1.28, 95% CI 1.00-1.63; p=0.018), triglycerides (OR 1.44, 95% CI 1.14-1.182; p=0.003), and cholesterol (OR 0.69, 95% CI 0.50-0.94; p=0.018).

In HCV genotype 3-infected patients, cholesterol levels, higher histological activity index (HAI) score, higher systolic blood pressure, and HCV RNA levels were factors predictive of steatosis. I

In genotype non-3 patients, trygliceride levels, HAI score, body mass index, and use of zidovudine (Retrovir), and of stavudine (Zerit), didanosine (Videx) or zalcitabine (Hivid) were independently associated with liver steatosis.

The probability of attaining SVR was not reduced by steatosis. Thus, sustained virological response (SVR) following treatment was achieved in comparable proportions of patients according to presence or absence of steatosis in the three arms of the study.

SVR significantly reduced the prevalence of steatosis in patients infected with HCV genotype 3 (41% at baseline vs. 7% after attaining SVR; p=0.0003), but not in those infected with other HCV genotypes (15% at baseline vs. 17% after achieving SVR; p=0.76).

Conclusions

The presence of hepatic steatosis was associated with HCV genotype 3, advanced stages of liver fibrosis and increased serum levels of, triglycerides, cholesterol and random elevated fasting blood glucose.

Liver steatosis was not related to the use of antiretroviral therapy, but in patients with HCV genotype non-3 the use of some nucleoside analogues was an  independent predictor of steatosis.

The probability of attaining SVR was not reduced by steatosis.

The achievement of SVR greatly reduced the prevalence of steatosis in patients infected with HCV-3, but not in those infected with other HCV genotypes, suggesting that other factors are involved in patients with HIV/HCV-coinfected patients.

11/28/05

References

1. FJ Torriani and others. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351:438-50.

2. M Rodríguez-Torres and others. Abstract 1197. Hepatic steatosis in patients with HIV-HCV coinfection enrolled in the AIDS PEGASYS Ribavirin International Coinfection Trial (APRICOT): clinical characteristics and response to treatment. 56th annual meeting of the American Association for the Study of Liver Diseases (56th AASLD). November 11-15, 2005. San Francisco, CA.