THERAPEUTIC EFFICACY OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS

Nonalcoholic steatohepatitis (NASH) as a distinct entity, which is rapidly gaining importance as a major cause of liver-related morbidity. One mechanism believed to be involved is insulin resistance. Recent studies have indicated that angiotensin II may contribute to insulin resistance, hepatic fibrosis, and tissue iron deposition. Based on this information, the authors have studied the effect of losartan, a selective angiotensin II type I receptor antagonist, in patients with NASH. Eight hypertensive patients with NASH were enrolled. Patients were given losartan at a dose of 50 mg/d for 48 weeks. Various serologic markers, as well as liver biopsy specimens, were evaluated before and after treatment. Seven patients completed the study. Serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase levels decreased significantly. Blood markers of hepatic fibrosis, including transforming growth factor-β1 (TGF-β1), serum hyaluronic acid, type IV collagen, and procollagen III N-terminal propeptide, significantly improved. Serum ferritin levels also decreased significantly although serum iron and hemoglobin levels were not changed. All patients had abnormally high homeostasis model assessment (HOMA)-R before treatment, indicating insulin resistance, which remained unchanged throughout the study. Body mass index, measurements of lipid profiles, renal function, serum electrolytes, plasma renin activities and serum angiotensin II were unchanged during the course of the study. In histologic evaluation, the degree of lobular steatosis remained unchanged, but hepatic necroinflammatory grade improved in five patients and fibrotic stage in four subjects. Degrees of hepatocellular injury and Mallory bodies improved in three patients. In two patients in whom iron deposition in hepatocytes was detected in the baseline biopsy, such changes had disappeared by the end of the study. The authors conclude that losartan significantly improved liver biochemical indices as well as hepatic necroinflammation.