Serum gamma-glutamyltransferase within its normal range predicts a chronic elevation of alanine aminotransferase: A four year follow-up study

Background: Previous epidemiological and experimental studies support the concept that serum gamma-glutamyltransferase (GGT) activity within its normal range is related to oxidative stress. Since oxidative stress plays a crucial role in the pathogenesis of various liver diseases, serum GGT may predict development of liver damage. Methods: A total of 6,523 healthy male workers with normal alanine aminotransferase (ALT, <35U/l) in a steel manufacturing company were followed for four years. Liver damage was defined as a chronic elevation of serum ALT (both 2001 and 2002). Results: After adjusting for age, body mass index, alcohol consumption, cigarette smoking, exercise, and baseline value of ALT, in comparison with the group whose GGT level was < 10 U/l, the adjusted relative risks for elevated ALT level among those with GGT levels 10-19, 20-29, 30-39, and over 40 U/l was 1.0, 2.5, 4.7, 7.4, and 12.0, respectively (P for trend < 0.01). More importantly, this association was similarly observed even among non-drinkers; the corresponding relative risks were 1.0, 1.8, 3.8, 5.6, and 6.2 (P for trend < 0.01). However baseline ALT did not predict abnormal GGT level four years later. Conclusion: Serum GGT levels within normal range predict incidence of chronic elevation of ALT. Oxidative stress might explain this relationship.