Approximately 30% of patients with chronic HCV infection show persistently normal alanine aminotransferase levels (PNAL). The prevalence of HCV carriers with normal liver seems to be very low (less than 15-20%). Liver disease is usually minimal/mild and fibrosis is generally absent or minimal, although the association of normal alanine aminotransferase (ALT) with cirrhosis or with liver cancer has been reported. In all studies, liver histology was, on average, significantly less severe in subjects with PNAL than with abnormal ALT. Although the majority of data seem to show that HCV carriers with normal ALT have mild and stable disease, with a favourable prognosis, several studies reported a significant progression of fibrosis in approximately 20-30% of the patients with ALT normality, and the development of HCC in some cases has been described, despite persistent ALT normality. Sudden worsening of disease with ALT increase and histological deterioration has been described after up to 15 years of follow-up, in particular in patients harboring genotype 2. As to antiviral treatment, it has been clearly stated that it no longer seems reasonable to affirm that sustained response rates for patients with normal ALT levels are any different than those for patients with elevated ALT levels when the combination of pegylated interferon (IFN) and ribavirin is used. The issue at hand is whether or not patients with mild disease should be treated. There are numerous other factors which impact on this decision, including genotype, histology, patients motivation, symptoms, co-morbid illness, and the age of the patient.