ment is also important. We thank Dowman and colleagues for giving us theopportunity to present the descriptive and nonparametric results.

STEPHEN HARRISON1

ELIZABETH BRUNT2

BRENT NEUSCHWANDER-TETRI3

1Gastroenterology Service, Department of Gastroenterology, BrookeArmy Medical Center, Fort Sam Houston, TX

2Department of Pathology and Immunology, Washington UniversitySchool of Medicine, St. Louis, MO

3Division of Gastroenterology and Hepatology, Saint Louis University,St. Louis, MO

Reference1. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for

overweight subjects with nonalcoholic steatohepatitis: a randomized, pro-spective trial. HEPATOLOGY 2009;49:80-86.

Copyright © 2009 by the American Association for the Study of Liver Diseases.Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/hep.23017Potential conflict of interest: Dr. Neuschwander-Tetri is a consultant for Gilead,

Amylin Pharmaceuticals, and Centofor.

Diagnosis, Management, and Treatment of Hepatitis C

To the Editor:

We read with great interest the updated American Association forthe Study of Liver Diseases practice guideline on the diagnosis, man-agement, and treatment of hepatitis C.1 In particular, the authorsshould be warmly congratulated for their practical and exhaustive ap-proach to patients with persistently normal alanine aminotransferase(PNALT) levels.

However, we have some concerns about the definition and man-agement of hepatitis C virus (HCV) carriers with PNALT proposed byGhany et al.1 We believe that the definition given in this article (“anALT value of less than 40 IU/L on 2 to 3 occasions separated by at leasta month over a period of six months”), although commonly used inclinical practice, could be misleading, as this observation period is tooshort and thus not adequate to discriminate between true HCV carrierswith PNALT levels and patients with only transient biochemical re-mission.2 Two or three normal alanine aminotransferase (ALT) valuesover a short-term period may not be representative of the true patternof ALT levels for a particular patient.3 Indeed, several studies haveshown that many subjects called HCV carriers with PNALT on thebasis of a 6-month observation period did suffer from ALT flaresduring the follow-up, showing histological worsening and fibrosis pro-gression after these flares.4,5

In light of these data, the Italian Association for the Study of theLiver6 suggested that the definition of HCV carriers with PNALTshould be made on the basis of at least nine normal ALT values 2months apart over an 18-month period. We have to be very cautiousbefore we define these persons as subjects with PNALT, given the risksof sudden exacerbation of the disease and a less benign natural historyin many of these apparently healthy carriers.

Furthermore, we have some comments to offer regarding the sug-gested management of these patients.1 The authors state that HCV-infected persons with normal ALT values do warrant treatment if liverbiopsy shows significant fibrosis. This approach seems to be too restric-tive, as it excludes from treatment many patients who might requiretherapy.

An International Clinical Workshop7 suggested that highly moti-vated, young patients with HCV 2 or 3 might have an excellent re-sponse to treatment and thus, in the absence of any contraindication,should receive treatment with pegylated interferon plus ribavirin ther-apy without the need for liver biopsy. On the contrary, in patientsharboring HCV type 1 or 4 (regardless of age) or in older patients(regardless of HCV type), liver biopsy might be invariably offered todecide the need for therapy, with treatment recommended only forpatients with evidence of liver disease (�F2).

This approach allows more tailored therapy for HCV carriers withPNALT,8 avoiding unnecessary biopsies in many patients and provid-ing the possibility of safe and highly effective treatment of HCV in-fection for selected patients.9,10

CLAUDIO PUOTI

RICCARDO GUARISCO

LIA BELLIS

LUCIA SPILABOTTI

Department of Internal Medicine and Liver UnitMarino General HospitalRome, Italy

References1. Ghany MG, Strader DB, Thomas DL, Seef LB. Diagnosis, management,

and treatment of hepatitis C: an update. HEPATOLOGY 2009;49:1335-1373.

2. Puoti C, Castellacci R, Montagnese F. Hepatitis C virus carriers withpersistently normal aminotransferase levels: healthy people or true pa-tients? Dig Liver Dis 2000;32:634-643.

3. Puoti C. HCV carriers with persistently normal aminotransferase levels:normal does not always mean healthy. J Hepatol 2003;38:529-532.

4. Puoti C, Castellacci R, Montagnese F, Zaltron S, Stornaiuolo M, Pace M,et al. Histological and virological features and follow-up of HCV carrierswith normal aminotransferase levels: the Italian Study of the Asymptom-atic C Carriers (ISACC). J Hepatol 2002;37:117-123.

5. Martinot-Peignoux M, Boyer N, Cazals-Hatem D, Bach-Nga P, GervaisA, Le Breton A, et al. Perspective study of anti hepatitis C virus positivepatients with persistently normal serum ALT with or without detectableserum HCV RNA. HEPATOLOGY 2001;34:1000-1005.

6. Puoti C, Guido M, Mangia A, Persico M, Prati D. Clinical management ofHCV carriers with normal aminotransferase levels. Dig Liver Dis 2003;35:362-369.

7. Zeuzem S, Alberti A, Rosenberg W, Marcellin P, Diago M, Negro F, et al.Review article: management of patients with chronic hepatitis C virusinfection and ‘normal’ alanine aminotransferase activity. Aliment Pharma-col Ther 2006;24:1133-1149.

8. Snoeck E, Hadziyannis SG, Puoti C, Swain MG, Berg T, Marcellin P, et al.Predicting efficacy and safety outcomes in patients with hepatitis C virusgenotype1and persistently ‘normal’ alanine aminotransferase levels treatedwith peginterferon alpha-2a (40KD) plus ribavirin. Liver Int 2008;28:61-71.

9. Puoti C, Pellicelli AM, Romano M, Mecenate F, Guarisco R, Barbarini G,et al. Treatment of HCV carriers with persistently normal alanine amino-transferase levels with peginterferon alfa-2a and ribavirin: a multicentricstudy. Liver Int. In press.

10. Puoti C. Hepatitis C virus with normal transaminase levels. Dig Dis 2007;25:277-278.

Copyright © 2009 by the American Association for the Study of Liver Diseases.Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/hep.23015Potential conflict of interest: Nothing to report.

322 CORRESPONDENCE HEPATOLOGY, July 2009