Relating serum GGT to ALT activity enhances its predictability on treatment outcome in chronic hepatitis C

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We read the article by Everhart and Wright1 with great interest, noting serum gamma glutamyl transferase (GGT) activity both as a predictor of therapy outcome and as a prognostic indicator for disease outcome in chronic hepatitis C patients, based on data raised at the end of a 7-year observation period. Data were obtained from patients who were enrolled in the HALT-C study, meaning these patients had treatment before and were experiencing an advanced stage of liver disease. Everhart and Wright were also able to show a combined effect of serum GGT activity and IL28B rs12979860 genotype. They described that GGT activity adds particularly to predictability in carriers of the nonfavorable T allele featured by low virological response rates when compared to favorable CC homozygotes with high virological response rates. In the past, we also made the observation that serum GGT activity is predictive for virological responsiveness in patients with chronic hepatitis C.2 However, we found that a combined parameter, namely, the ratio of GGT and alanine aminotransferase (ALT) serum activity (ratio GGT/ALT) was clearly superior to serum GGT or serum ALT alone as a measure to indicate viral eradication. Although done in a much smaller and less homogenous cohort of out-patients, we were able to confirm our retrospective observation in a prospective approach.3 Moreover, with regard to IL28B rs12979860 genotypes, we recently were able to show that the GGT/ALT ratio improved IL28B rs12979860 genotype predictive efficiency from an odds ratio (OR) of 2.8, up to an OR of 26.7 in a cohort of 264 HCV type 1 patients.4, 5 In our hands the pretreatment GGT/ALT ratio has proven to be a more advantageous predictor than GGT or ALT serum activities alone. We therefore suggest that applying the ratio to the dataset analyzed by Everhart and Wright should yield even more persuasive data. Ahmad Amanzada, M.D. Giuliano Ramadori, M.D. Sabine Mihm, Ph.D. University Medical Center Goettingen, Department of Gastroenterology and Endocrinology Goettingen, Germany