HCV-Positive Patients with Normal Aminotransferase Levels

How does one manage patients with HCV infections who have normal aminotransferase levels?

How does one manage patients with hepatitis C virus (HCV) infections who have normal aminotransferase levels: observe, ignore, or treat? Some earlier studies have suggested that HCV-positive patients with persistently normal alanine aminotransferase (ALT) levels tend to have slower progression of liver disease than do patients with elevated ALT levels. In two new studies, researchers evaluated epidemiologic and histologic differences between HCV-positive patients with and without abnormal liver-enzyme levels.

Italian investigators assessed epidemiologic, immunologic, and histologic differences between 40 patients with elevated ALT levels and 24 patients with normal levels. Liver biopsies were obtained at baseline and at 10 years in the normal-ALT group. Immunologic differences between the two groups were evaluated at 0, 5, and 10 years by assessing proliferating cellular nuclear antigen (PCNA) levels in liver specimens, interferon- production in lymphocytes, or both. During the first 4 years, 22% of patients with normal baseline ALT levels developed elevated levels, but no additional patients developed elevated levels thereafter. Sex was the only demographic factor that differed statistically between groups (elevated-ALT group, 60% men; normal-ALT group, 37.5% men; P<0.05). Histologically, the elevated-ALT group had significantly higher degrees of fibrosis and steatosis at baseline than did the normal-ALT group. Immunologically, PCNA levels were significantly higher at all time points in the elevated-ALT group than in the normal-ALT group. During follow-up, patients with persistently normal ALT levels exhibited no significant histologic progression or immunologic changes.

Another group evaluated the clinical, virologic, and histologic characteristics of 2473 HCV-positive patients with normal or elevated liver-enzyme levels from three earlier randomized controlled international trials. As in the Italian trial, a significantly higher proportion of normal-ALT patients than elevated-ALT patients were women (P<0.01). Normal-ALT patients had milder histologic damage than did elevated-ALT patients (P<0.01), although 10% of normal-ALT patients did have bridging fibrosis at baseline. Of 68 normal-ALT patients who were followed for 72 weeks, 53% developed liver-enzyme elevations.

Comment: Although these studies use different designs, they provide insight into how to approach HCV-positive patients with normal ALT levels. First, a few such patients will have significant liver fibrosis, so the decision to treat should be based on biopsy results. Second, many patients with initially normal liver-enzyme levels ultimately will develop abnormal levels, so close follow-up is necessary. Third, if long-term persistence of normal liver-enzyme levels is demonstrated, treatment might not be required, as substantial histologic progression occurs only rarely.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology September 8, 2006

Citation(s):

Persico M et al. Hepatitis C virus carriers with persistently normal ALT levels: Biological peculiarities and update of the natural history of liver disease at 10 years. J Viral Hepat 2006 May; 13:290-6.