• Potential conflict of interest: Nothing to report.


We thank Dr. Puoti and colleagues for their interest in our article, and appreciate the identification of an important issue in everyday clinical practice. Not only do the authors make a valid point about the potential disparity between a “normal” alanine aminotransferase (ALT) concentration and the presence of clinically important hepatic fibrosis, they also raise two further issues. First, there is continuing debate as to what constitutes a “normal ALT” level.1–3 There is evidence to suggest that a value above 19 IU/L in a woman and 25 IU/L in a man should be considered abnormal, whereas the upper limit of the normal range at many clinical laboratories (be this in community or academic medical center settings) is 40 U/L, and in some instances higher still. Second, we believe that the authors may have understated the importance of the role of liver biopsy in management of patients with a normal ALT concentration and chronic hepatitis C virus (HCV) infection: it is the information that liver histology provides in the context of the clinical picture that is critical. These data may mean the difference between embarking upon antiviral therapy or not. For example, a patient with minimal fibrosis but an otherwise unfavorable treatment outcome profile (obese, African American, male, genotype 1) could very well be counseled to wait for additional therapies, particularly if his duration of infection is longstanding. Alternatively, the clinician might be more aggressive with a young patient having fibrosis that borders on advanced, and who has a favorable treatment outcome profile. Thus, biopsy and histological assessment can play an important role in decision-making in the setting of HCV with normal aminotransferases. To the extent that human immunodeficiency virus (HIV) modifies the fibrogenic response to HCV, as intimated by Puoti et al., we believe histologic assessment is often even more important in this setting.

Therefore, we endorse the view that liver biopsy is potentially very useful in patients with HCV, with or without HIV.

Don C. Rockey M.D.*, Stephen H. Caldwell M.D.†, Zachary D. Goodman M.D.‡, Rendon C. Nelson M.D.§, Alastair D. Smith MB, ChB, FRCP (Glasg)¶, * Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, † Gastroenterology Division, University of Virginia, Charlottesville, VA, ‡ Armed Forces Institute of Pathology, Washington, DC, § Department of Radiology, Duke University Medical Center, Durham, NC, ¶ Department of Gastroenterology Division Department of Medicine, Duke University Medical Center, Durham, NC.