Lovastatin decreases mortality and improves liver functions in fulminant hepatic failure from 90% partial hepatectomy in rats

Background/Aims: Liver insufficiency occurs when the liver cannot perform c ritical functions such as ammonia metabolism, gluconeogenesis, or productio n of coagulation factors. The hypothesis of this study was that decreased f unction of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastat in is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits ch olesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver function s, and lovastatin might prevent these changes. Methods: Rats received 90% partial hepatectomy (90% PI I), and either lovas tatin or vehicle alone daily, Survival and liver functions were assessed. Results: Lovastatin increased survival to 58% (vs, 6% in controls that rece ived 90% PH without drug), decreased the peak ammonia level to 427 mu M (vs , 846 mu M in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s i n controls), and decreased the peak activated partial thromboplastin time t o 29 s (vs. 39 s in controls), The full survival and metabolic benefits wer e observed when lovastatin was started at 30 min after 90% PH, but lovastat in was less efficacious when started at later times. Conclusions: Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.