Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality

Background/Aims: Hepatotoxin-induced rat models of liver cirrhosis are limited by the wide heterogeneity of cirrhosis produced. The present study developed a modified, reliable, and reproducible technique by which hepatic and systemic responses to thioacetamide during induction of cirrhosis were monitored by weekly weight changes. Methods: Male Wistar rats (200-230 g) were divided into three groups. Group 1 (n = 20) received continuous administration of 0.03% (w/v) thioacetamide in the drinking water for 12 weeks. Group 2 (it = 20) received the same concentration of 0.03% thioacetamide as an initial concentration that was modified according to weekly weight changes in response to thioacetamide during the induction of cirrhosis. Group 3 (it = 6) received normal water and served as controls. Results: Mortality of Group 1 was 30% and the production of cirrhosis was only 45%. In contrast, there were no deaths in Group 2 and well-developed macronodular cirrhosis was found in 90% of the rats which was associated with significant portal hypertension, as indicated by increased portal venous pressure (13.6 +/- 0.4 vs. 9.1 +/- 0.3 mmHg, cirrhotic vs. control, respectively, P < 0.01, Student's unpaired t-test). Conclusions: Variations in responses to thioacetamide can be easily monitored by weekly weight changes to reduce mortality to zero and simultaneously increase the production and quality of cirrhosis induced in rats. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.