Background:  Liver fibrosis progression is slower in hepatitis C virus (HCV) –mono-infected patients with persistently normal alanine aminotransferase (ALT) than in patients with elevated ALT levels. Differences in liver fibrosis staging between HIV⁺ and HIV^– patients with chronic hepatitis C having persistently normal ALT have not been assessed.

Methods:  All patients with detectable serum HCV RNA and persistently normal ALT who underwent liver fibrosis assessment using elastometry (FibroScan) since 2004 at 3 different European clinics were evaluated. None had received HCV treatment. Persistently normal ALT was defined as aspartate aminotransferase (AST)/ALT levels below the upper limit of normality during at least 3 consecutive determinations made within the last 12 months. Liver fibrosis staging was defined as mild (Metavir F0-F2) if ≤9.5, moderate (F3) if 9.5 to 12.5, and severe (F4) if >12.5 kPa.

Results:  We compared 448 HCV-mono-infected patients with 118 HCV/HIV-co-infected patients. HIV^– patients were older (mean age, 52 vs 43 years; p <0.01), more frequently female (63 vs 37%; p <0.01) and admitted less often alcohol intake >40 g/day (18 vs 26%; p = 0.1). Mean serum HCV RNA was similar in both groups (5.9 vs 5.8 log IU/mL). HCV genotype distribution was different in HIV^– (G1, 55%; G2, 23%; G3, 6%; G4, 14%) and HIV⁺ patients (G1, 52%; G2, 4%; G3, 11%; G4, 32%). Of HIV⁺ patients, 78.6% were on HAART and their mean CD4 count was 518 cells/mL. Of HIV^– patients, liver fibrosis was mild in 93%, moderate in 3%, and severe in 3%. These figures were 91%, 4%, and 5% in HIV⁺ patients. In the univariate and multivariate logistic regression analysis, the only factor that was associated with having moderate or severe liver fibrosis was older age (OR 1.04, 95%CI 1.02 to 1.07; p <0.001). After adjusting by age, HCV/HIV-co-infected patients tended to have moderate to severe liver fibrosis more often than HCV-mono-infected patients (OR 2.2, 95%CI 0.9 to 5.2; p = 0.06).

Conclusions:  Nearly 10% of HIV/HCV-co-infected patients with persistently normal ALT have moderate to severe liver fibrosis (Metavir F3 to F4), which is seen in only 7% of HCV-mono-infected patients. After adjusting for age, HIV⁺ patients with persistently normal ALT tend to show more advanced liver fibrosis.