Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ≤ 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT ( ). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease. 1. Introduction Hepatitis C virus (HCV) infection is reported to have a prevalence of approximately 3% worldwide [1]. Almost 80% of those infected go on to develop chronic infection. Majority of patients with chronic HCV have a mild, asymptomatic elevation in serum transaminase levels with no significant clinical symptoms. Around 25% of patients with chronic HCV have persistently normal alanine aminotransferase (PNALT) [2]. Definition of normal alanine aminotransferase (ALT) has changed over time and reference range for normal ALT differs based on different laboratory cutoffs. Prati et al. [3] in 2002 suggested new cutoffs with 30？U/L (international unit) for men and 19？U/L for women compared to 40？U/L and 30？U/L for men and women, respectively. This resulted in improved sensitivity but decreased specificity. Similarly, definition of PNALT differs widely. A 2009 American Association for the Study of Liver Disease (AASLD) practice guideline suggested an ALT value of 40？U/L on 2-3 different occasions separated by at least a month over a period of 6 months [4]. Others have used 3 different ALT levels equal to or below upper limit of normal (ULN) separated by at least 1 month and sometimes over a period of 18 months [5]. Thus, there is no consensus on a universal definition of PNALT. It was generally thought that people with PNALT have a mild liver disease and the degree of liver fibrosis is minimal [6–14].
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