Nonalcoholic steatohepatitis (NASH) may cause progressive hepatic
fibrosis,
cirrhosis, and
hepatocellular carcinoma. Treatment, thus far, has been restricted to diet and
weight loss, but without compelling results. In this study we aimed to evaluate the efficacy of
orlistat therapy in obese patients with NASH. Fourteen obese patients with NASH underwent liver biopsy prior to and subsequent to 6 months treatment with
orlistat (120 mg tid). Hepatic fat extension was graded as normal, mild, moderate, or severe. Hepatic
fibrosis was scored on a scale from 0 to 4, with 0 denoting no
fibrosis and 4,
cirrhosis. Portal
inflammation was scored as 0-3, with 0 = normal, 1 = mild, 2 = moderate, and 3 = severe
inflammation. Fourteen patients had NASH associated with diabetes,
hyperlipidemia, or
obesity.
Orlistat reduced fatty infiltration in 10 patients (70%; P<0.01), 3 of whom had normal liver fat content
after treatment.
Orlistat improved inflammatory activity by 2 grades in 28% and by 1 grade in 50% of patients and effected no change in 22% of patients. Five patients (35%) returned to normal inflammatory activity.
Orlistat improved hepatic
fibrosis by 2 grades in three patients (21%) and by 1 grade in seven patients (50%). There was no change in four patients (28%).
Orlistat lowered
aminotransferases levels, total
cholesterol,
triglycerides and
low-density lipoprotein, respectively.
Insulin resistance index and malonyl dialdehyde levels improved significantly after
orlistat therapy, whereas HbAic remained unchanged. In conclusion, in obese patients with NASH,
liver fibrosis and
inflammation improved after
therapy with
orlistat.