Diagnosis, Management, and Treatment of Hepatitis C.

We read with great interest the updated American Association for the Study of Liver Diseases practice guideline on the diagnosis, management, and treatment of hepatitis C.1 In particular, the authors should be warmly congratulated for their practical and exhaustive approach to patients with persistently normal alanine aminotransferase (PNALT) levels. However, we have some concerns about the definition and management of hepatitis C virus (HCV) carriers with PNALT proposed by Ghany et al.1 We believe that the definition given in this article ("an ALT value of less than 40 IU/L on 2 to 3 occasions separated by at least a month over a period of six months"), although commonly used in clinical practice, could be misleading, as this observation period is too short and thus not adequate to discriminate between true HCV carriers with PNALT levels and patients with only transient biochemical remission.2 Two or three normal alanine aminotransferase (ALT) values over a short-term period may not be representative of the true pattern of ALT levels for a particular patient.3 Indeed, several studies have shown that many subjects called HCV carriers with PNALT on the basis of a 6-month observation period did suffer from ALT flares during the follow-up, showing histological worsening and fibrosis progression after these flares.4, 5 In light of these data, the Italian Association for the Study of the Liver6 suggested that the definition of HCV carriers with PNALT should be made on the basis of at least nine normal ALT values 2 months apart over an 18-month period. We have to be very cautious before we define these persons as subjects with PNALT, given the risks of sudden exacerbation of the disease and a less benign natural history in many of these apparently healthy carriers. Furthermore, we have some comments to offer regarding the suggested management of these patients.1 The authors state that HCV-infected persons with normal ALT values do warrant treatment if liver biopsy shows significant fibrosis. This approach seems to be too restrictive, as it excludes from treatment many patients who might require therapy. An International Clinical Workshop7 suggested that highly motivated, young patients with HCV 2 or 3 might have an excellent response to treatment and thus, in the absence of any contraindication, should receive treatment with pegylated interferon plus ribavirin therapy without the need for liver biopsy. On the contrary, in patients harboring HCV type 1 or 4 (regardless of age) or in older patients (regardless of HCV type), liver biopsy might be invariably offered to decide the need for therapy, with treatment recommended only for patients with evidence of liver disease (>F2). This approach allows more tailored therapy for HCV carriers with PNALT,8 avoiding unnecessary biopsies in many patients and providing the possibility of safe and highly effective treatment of HCV infection for selected patients.9, 10 Claudio Puoti*, Riccardo Guarisco*, Lia Bellis*, Lucia Spilabotti*, * Department of Internal Medicine and Liver Unit, Marino General Hospital, Rome, Italy.