Background:  Liver fibrosis progression is slower in HCV-infected patients with persistently normal alanine aminotransferase (ALT) (PNALT) than in those with elevated ALT levels. The prevalence and significance of normal ALT in patients with HIV/HCV co-infection is not well established.

Methods:  All HIV⁺ patients with detectable HCV RNA who underwent liver fibrosis assessment using elastometry (FibroScan) at our institution were evaluated. Co-infected patients with PNALT were identified and were compared with a matched control group of patients with elevated ALT. PNALT was defined as AST/ALT levels below the normal upper limit during at least three consecutive determinations made within the last 12 months.

Results:  We compared 87 patients with PNALT with 133 patients with elevated ALT. Mean age was similar in both groups (43 and 42 years); 17% of PNALT patients and 23% of those with elevated ALT had previously being exposed and failed interferon-based therapies. Liver fibrosis staging significantly differed in both groups of patients (see the table). PNALT was significantly associated with female gender (42% vs 26%; p = 0.012) and HCV genotype 4 or 1 (33% vs 6%, p = 0.001 and 67% vs 53%; p = 0.04; respectively). In contrast, patients with elevated ALT were more often on HAART (90% vs 75%, p = 0.006) and were infected with HCV genotype 3 (24% vs 10%, p = 0.01).

PNALT patients had more platelets (mean 214 vs 160x1000/µL, p <0.001) and CD4 counts (mean 567 vs 475 cells/µL, p = 0.09) than patients with elevated ALT. Finally, PNALT patients had significantly lower serum HCV RNA than patients with elevated ALT (5.8 vs 6.16 log, p = 0.004). Advanced liver fibrosis (F3-F4) did not differ significantly in PNALT patients infected with distinct HCV genotypes (HCV-1, 13%; HCV-2, 33%; HCV-3, 11% and HCV-4, 14%) and no significant differences were observed between previously HCV-treated and untreated patients (20% and 13%, respectively, p = 0.21).

Conclusions:  Nearly 15% of HIV/HCV-co-infected patients with PNALT have advanced liver fibrosis (F3-F4). PNALT is significantly more frequent in women and HCV genotype 4.