Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA

A significant proportion of patients with detectable antibodies to hepatiti s C virus have normal serum alanine transaminase levels. Our aim was to stu dy the outcome of this group. Between 1992 and 1999, 135 consecutive anti-H CV-positive patients with persistently normal ALT were followed for 3.6 +/- 2.3 years (0.5 to 8.5 years), 108 had a liver biopsy at inclusion, and 24 had a second liver biopsy 3.5 +/- 1.0 years later. Serum HCV RNA was detect able with PCR in 94 patients (69%) and not detectable in 41 patients (31%). Patients with and without detectable serum HCV RNA had similar epidemiolog ical characteristics. Serum ALT levels and anti-HCV ratio were lower (P = . 001), and histological lesions had lower grade and stage in patients withou t detectable serum HCV RNA (P = .001). Liver HCV RNA was not detectable wit h PCR in the 12-serum HCV RNA-negative patients tested. During follow-up, a ll patients without detectable serum HCV RNA remained HCV RNA-negative and kept normal serum ALT; all patients with detectable serum HCV RNA remained HCV RNA-positive, 20 (21%) had a slight fluctuation of serum ALT above the upper limit of normal. No significant changes were observed in the liver le sions of the 24 patients who underwent a second liver biopsy. In anti-HCV-p ositive patients with persistently normal serum ALT, histological lesions a re significantly lower in HCV RNA-negative than in HCV RNA-positive patient s. During follow-up, the HCV RNA status of patients remained unchanged; 21% of the patients with detectable serum HCV RNA had slight increase in serum ALT levels, but histological lesions remained stable.