Should we treat HCV carriers with normal ALT levels? The '5Ws' dilemma.

Approximately 30% of patients with chronic HCV infection have persistently normal ALT levels. Although formerly referred to as 'healthy' or 'asymptomatic' HCV carriers, and thus historically excluded from antiviral treatment, it has now become clear that the majority of these patients have some degree of histological liver damage that may be significant in up to 20% of cases and might progress towards a more severe degree of liver fibrosis. A significant proportion of patients experience periods of increased serum ALT associated with enhanced disease progression. However, controversies still exist in clinical practice regarding the definition of 'persistent' ALT normality, the virological and histological features of these subjects, the need for liver biopsy, the role of noninvasive tools for the assessment of liver fibrosis, the natural history and the usefulness of antiviral treatment. The advent of new therapeutic options (pegylated interferon plus ribavirin) has shifted treatment targets towards the eradication of underlying infection, with therapy decision based on age, severity of disease and likelihood of response rather than on aminotransferase levels. This review is aimed at approaching the main unresolved issues on this topic, trying to give evidence-based answers to the more frequently asked questions from patients and their physicians.