Liver fibrosis progressed faster than expected in more than one quarter of people coinfected with HIV and hepatitis C virus (HCV), despite little or no fibrosis on their initial biopsy, according to results of a 61-person study presented in Boston, Massachusetts at the 12th Conference on Retroviruses and Opportunistic Infections.
Based on these results, principal investigator Mark Sulkowski, MD, of Johns Hopkins University suggested that coinfected individuals with little or no fibrosis may need a liver biopsy at least every 3 years, rather than the 3- to 5-year interval recommended for people infected only with HCV.
HCV treatment guidelines advocate liver biopsy before anti-HCV therapy to gauge fibrosis—mainly to identify people with little or no fibrosis in whom therapy may be deferred. However, it is not clear to what extent these guidelines apply to HIV/HCV-coinfected patients.
To provide prospective data on the rate of fibrosis progression in HCV/HIV-coinfected persons with little or no fibrosis on initial biopsy, Dr. Sulkowski and colleagues undertook a study comparing sequential biopsies done in 61 coinfected people. Ishak fibrosis scores were determined by a single pathologist reading liver samples. Median time between biopsies was 2.84 years (interquartile range, 2.05 to 3.41 years).
Excluding coinfected persons with advanced (F5 or F6) liver disease on the first biopsy, the Hopkins pathologist rated 53% of biopsies F0, 31% F1, 3% F2, and 12% F3 or F4. The second biopsy showed regression, no progression, or less than 1-stage progression in 73%, but 2- or 3-stage progression in the remaining 17%.
Among those with an F0 or F1 score on the first biopsy, 28% had at least a 2-stage jump in fibrosis on their second biopsy.
To determine what characteristics might predict rapid fibrosis progression in coinfected patients, investigators compared 14 people who had more than a 2-stage surge and 37 who had no change in fibrosis score. Patients with a 2-stage change were more likely to have persistently elevated levels of aspartate aminotransferase (AST) between the first and second biopsy (P = .05) than patients with no fibrosis change. Investigators noted other differences suggesting a correlation between faster fibrosis progression and poorer HIV control (eg, frequency of CD4+ cell counts >200 cells/mm3 between first and second biopsies), but none reached statistical significance, possibly due to the small sample size.
Overall, the coinfected cohort studied by the Hopkins group consisted largely of African-Americans (86%) and people with a history of injection drug use (69%). The median duration of HCV infection at first biopsy was 23.8 years; 21% had a CD4+ cell count below 200 cells/mm3, and 57% had an HIV-1 RNA level of less than 400 copies/ml.
Dr. Sulkowski called for more research to identify predictors of fibrosis progression in HCV/HIV-coinfected people. Until such predictors emerge, he advised, coinfected people with mild disease on biopsy should be closely monitored for progression.
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Sulkowski M et al. Unexpected significant liver disease among HIV/HCV-co-infected persons with minimal fibrosis on initial liver biopsy. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 121, 2005.