Orlistat Reverse Fatty Infiltration and Improves Hepatic Fibrosis in Obese Patients with Nonalcoholic Steatohepatitis (NASH)

Abstract

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.

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

“…The lipase inhibitor orlistat, which prevents lipid absorption, was found to reduce hepatic steatosis and fibrosis (Hussein et al, 2007) and was reported to positively influence serum ALT levels as well as steatosis, even if no weight loss was achieved (Zelber-Sagi et al, 2006). Weight loss as a result of administration of norepinephrine and the serotonin reuptake inhibitor sibutramine, which suppresses appetite and stimulates thermogenesis, was reported to decrease levels of ␥-glutamyl transferase (GGT) and serum transaminases (Sabuncu et al, 2003).…”

Review: Treatment options for nonalcoholic fatty liver disease

“…Three small studies have evaluated orlistat in NAFLD [Hussein, 2007;Zelber-Sagi, 2006;Harrison et al 2004]. Only one of these was a double-blind placebo-controlled randomized clinical trial [Zelber-Sagi et al 2006].…”

Review: Treatment options for nonalcoholic fatty liver disease

“…Sibutramine, a serotonin and norepinephrine reuptake inhibitor, promotes satiety and increases energy expenditure by stimulating thermogenesis. At least four studies have examined the effects of these medications on NAFLD [Hussein et al 2007;Harrison et al 2004Harrison et al , 2009Sabuncu et al 2003]. Sabuncu and colleagues treated patients with sibutramine or orlistat along with dietary restriction in an open-label study for 6 months [Sabuncu et al 2003].…”

“…Improvements were noted in homeostatic model assessment (HOMA) scores, aminotransferases, and sonographic findings, but liver biopsies were not obtained. Three studies have evaluated the effect of treatment with orlistat over 6 months [Hussein et al 2007;Harrison et al 2004Harrison et al , 2009. Paired biopsies revealed improvements in steatosis, inflammation, and fibrosis in most patients.…”