HCV carriers with normal aminotransferase levels: normal does not always mean healthy

BACKGROUND Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels (PNALT), and another 40% have minimally raised ALT values. Although formerly referred to as healthy or asymptomatic HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage. Controversies still exist regarding the definition of persistent ALT normality, the virological and histological features of these subjects, and the natural history and optimal management of chronic hepatitis C (CHC) with normal ALT. Most patients with normal ALT have histologically proven liver damage that may be significant (> F2) in up to 20% of patients, and might progress toward more severe degree of liver fibrosis. A significant proportion of patients (≥ 20%) experiences periods of increased serum ALT (flare) associated with disease progression.
AIM OF THE STUDY The introduction of the new combination therapy of PEG-IFN plus ribavirin allowed response rates higher than 50%, with a favourable risk-benefit ratio also in patients with benign or slow progressive disease. Given the efficacy of the new treatments, which soon became the standard of care for CHC, it has been suggested that the issue of whether or not to treat subjects with PNALT should be re-evaluated. ALT levels may have less importance in deciding who should be treated. Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patient's motivation, symptoms, extrahepatic manifestations, comorbid illness. The role of non-invasive tools for the assessment of liver fibrosis (transient hepatic elastography) remains to be further validated.