Effect of hospitalisation on liver enzymes in healthy subjects

Objectives: The aims of the present evaluation were to determine whether th e elevations in liver enzymes observed in phase-I trials are more common in subjects being hospitalised than in ambulatory subjects and to assess the relevance of these elevations. We therefore investigated the effect of hosp italisation on liver enzyme levels in subjects of all phase-I trials of suf ficient length performed at the two Human Pharmacology Centres of Boehringe r Ingelheim, located in Biberach and Ingelheim, Germany, over a 10-year per iod. Methods: The evaluation was based on 29 phase-I trials conducted between 19 87 and 1996. These trials consisted of at least 4 days of observation of 22 0 subjects on placebo treatment in 273 trial participations. The mean chang es (transformed into reference ranges) in the liver enzymes alkaline phosph atase, gamma glutamyl transpeptidase, aspartate aminotransferase, alanine a minotransferase and the AST/ALT ratio of hospitalised subjects were compare d with those of ambulatory subjects. Results: A small but statistically significant increase in the mean of the parameters GGT, AST and ALT during phase-I trials was observed in hospitali sed subjects compared with ambulatory subjects. The increases were: 8% of t he reference range width for GGT, 8% for AST and 17% for the ALT, although the differences were small in absolute terms. A relevant increase (defined as an increase to above the reference range or by at least 50% of the refer ence range) was more common in hospitalised subjects. Conclusion: Hospitalisation, although it is believed to protect subjects fr om confounding environmental factors, can itself be associated with increas es in liver enzyme levels. The definition of a relevant increase can be use d to identify subjects who need further evaluation. The cause of the increa se in liver enzyme levels remains unclear.