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Fibrosis Progression in HIV/HCV Coinfected Patients with Paired Liver Biopsies: evaluation of risk factors
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Reported by Jules Levin
An Italian research group (M Schiavini, Luigi Sacco Hospital, Il dept Infectious Diseases, Milano, Italy, et al) reported one of two studies of paired liver biopsies in coinfected patients. The second study was from a French group & a link to this study report on the NATAP website is at the end of this report. Together, this makes three such studies, the third reported by Mark Sulkowski (Johns Hopkins) at CROI 2005, all showing the accelerated progression of HCV in HIV+ patients, supporting the idea that HIV can accelerate HCV in a significant proportion of patients. Perhaps HAART may slow HCV in some patients, PERHAPS, but it appears that for many patients despite HAART HCV is accelerated. It is very difficult to sort out in whom HCV is accelerated without serial liver biopsies, however this is not feasible and as is found in these 3 studies over the course of 3-4 years liver disease progessed quickly in a significant proportion of patients, suggesting the justification for initiating HCV therapy at an early stage of liver disease in coinfection.
Schiavini said the aim of the study was to analyze fibrosis progression in HCV/HIV coinfected patients undergoing a subsequent liver biopsy and to find out possible associated risk factors. Since Jan 1985 to Jan 2002 HIV/HCV coinfected patients followed at the Il Dept of Infectious Diseases of L. Sacco Hospital in Milan, Italy, with paired biopsies have been respectively evaluated. All specimens were read double-blinded by two pathologists, who were not aware of the clinical or biological data of the patients. The stage of fibrosis was considered progressed when an increase of at least one stage in the second biopsy occurred. The fibrosis progression rate (FPR) was defined as the difference between the scores at 2 consecutive biopsies divided by the time in years elapsed between these two biopsies. Correlation with epidemiological, clinical, biochemical, and immunological data was applied.
Paired liver biopsies were available for 36 patients. The median time between two consecutive biopsies was 54 months (IQR 50-86). 56% of patients received a monotherapy or a combination of 2 NRTIs for HIV; 44% did not receive any antiretroviral therapy. 33 of 36 patients have been treated with interferon monotherapy after the first biopsy: two patients achieved SVR after treatment. Fibrosis progression occurred in 18 of 36 patients (50%). The median FPR was 0.23 (95% CI 0.19-0.43). The study authors said, at this rate of fibrosis progression, the median expected time to cirrhosis was 21 years (95% CI 11.6-26.3), but we know that liver disease progression is not linear so progression may accelerate for some patients. The mean staging score at the second biopsy was significantly higher than at the first one (2.1 vs 1.2, p=0.04). In an univariate analysis, heavy alcohol intake, HBV coinfection, and lack of antiretroviral treatment, were associated with an increased risk of fibrosis, but they did not reach statistical significance. either in a univariate or multivariate analysis a decrease of CD4 cell count more than 10% between the two biopsies (OR 6.85 p=0.002) was significantly associated with liver fibrosis progression. The authors said, the 2 patients who achieved SVR to interferon did not show a progression of liver fibrosis.
The authors summarized that it is mandatory to evaluate HIV/HCV coinfected patients for anti-HCV therapy and to increase CD4 counts through HAART in order to reduce the risk of fibrosis progression and to slow liver disease.
Link to report of French study at Workshop, in this study 85% received HAART.
Accelerated HCV Progression in HIV: paired liver biopsies (01/25/06)
Link to report of Sulkowski study reported at CROI, 82% of patients received ART:
Accelerated Liver Disease Progression in HCV/HIV Coinfection
- (03/07/04)
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