Reply:
Authors: Bernd Kronenberger, Eva Herrmann, Florence Micol, Michael von Wagner, Stefan Zeuzem
Journal: Hepatology (2005)

We thank Puoti et al. for the interest in our article and would like to provide some additional statistical results on patients with chronic hepatitis C and low normal (healthy) alanine aminotransferase (ALT) levels, high normal ALT levels and occasional ALT flares. Patients with healthy ALT levels (n = 6) compared with patients with high normal ALT levels (n = 14) showed a difference in the efficacy of blocking virus production ϵ (P = .049) but no difference in the infected cell loss before treatment δ (P = .13) and during treatment mδ (P = .19). This result agrees with the observation in our article that differences in viral kinetics between patients with normal ALT levels and elevated ALT levels are typically overcome during treatment, leading to similar kinetic profiles after the second week of treatment and comparable sustained virological response rates in both groups. Patients with minor ALT flares (5 of 20 patients) compared with patients with normal ALT levels showed no difference in viral kinetic parameters ϵ, δ, and mδ (P > .2). This result indicates that minor ALT flares do not affect the responsiveness to antiviral therapy. However, it must be kept in mind that these patients may not have been representative of the subgroup of patients with normal ALT and occasional ALT flares, because many of these patients have been excluded due to the enrolment criteria of the trial. Information on steatosis was available in 18 of 20 patients with persistently normal ALT levels and in 17 of 19 patients with elevated ALT levels. Presence and severity of steatosis was not different between patients with healthy ALT levels (moderate steatosis in 1 [20%] of 5 patients) and those with high normal ALT levels (minimal steatosis in 3 [23%] of 13 patients, P > .2) and between patients with minor ALT flares (minimal steatosis in 1 [20%] of 5 patients) and those with persistently normal ALT levels (minimal and moderate steatosis in 2 [15%] and 1 [8%] of 13 patients, respectively, P > .2). Due to the relatively small number of patients with healthy ALT levels and patients with minor ALT flares it is not possible to exclude liver steatosis as a possible cause of ALT elevation. Regular alcohol consumption and drug intake were exclusion criteria and can be neglected as causes of ALT elevation in our study. Finally, Puoti et al. suggested that liver steatosis should be ruled out as a possible cause of gamma glutamyltranspeptidase (GGT) elevation. Steatosis was found in 8 (47%) of 17 patients with elevated GGT levels and 4 (22%) of 18 patients with normal GGT levels (P = .12). In the subgroup of patients with persistently normal ALT levels, no steatosis, minimal steatosis, or moderate steatosis was observed in 10, 2, or 1 of 13 patients with normal GGT levels, respectively, and in 4, 1, and none of 5 patients with elevated GGT levels, respectively. The presence and severity of steatosis was not different between both groups (P > .2). Thus, the presence of steatosis does not appear to be a major cause of GGT elevation in patients with persistently normal ALT levels. Bernd Kronenberger M.D.*, Eva Herrmann Ph.D.*, Florence Micol Ph.D.*, Michael von Wagner M.D.*, Stefan Zeuzem M.D.*, * Internal Medicine II, Saarland University Hospital, Homburg/Saar, Germany.