Use of Orlistat in Obese, Non-Alcoholic Steatohepatitis Patients
Use of Orlistat in Obese, Non-Alcoholic Steatohepatitis Patients
Background: Treatment options for non-alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy.
Aim: To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH.
Methods: Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained.
Results: Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4-39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14-5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 -54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79-48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients.
Conclusions: Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost-efficacy in comparison to diet and exercise alone.
The most recent National Health and Education Survey (NHANES) revealed that 30.5% of adult Americans are obese and the percentage continues to increase. As a result, the incidence of diabetes mellitus is also increasing. Since non-alcoholic steatohepatitis (NASH) is strongly associated with obesity and diabetes, it is likely that the incidence of NASH is increasing as well. Natural history studies show that up to 16% of patients with NASH may progress to cirrhosis and some of these patients will develop end-stage liver disease and/or possibly hepatocellular carcinoma, necessitating liver transplant. Currently, therapeutic options are limited. Standard practice has been to advocate weight loss and exercise, but supporting data are limited to small trials with varied results.
Orlistat, a reversible inhibitor of gastric and pancreatic lipases, blocks the absorption of approximately 30% of dietary triglycerides and was approved by the FDA in 1999 for the management of obesity. Data indicate that 38% of patients treated with orlistat and a low-fat diet for 1 year lose at least 5-10% of their baseline bodyweight. The effect of orlistat on NASH is unknown. Consequently, we designed a pilot trial of orlistat therapy for obese NASH patients. The aim of our study was to evaluate the efficacy of orlistat, given for 6 months to patients with obesity and histologically confirmed NASH.
Background: Treatment options for non-alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy.
Aim: To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH.
Methods: Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained.
Results: Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4-39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14-5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 -54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79-48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients.
Conclusions: Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost-efficacy in comparison to diet and exercise alone.
The most recent National Health and Education Survey (NHANES) revealed that 30.5% of adult Americans are obese and the percentage continues to increase. As a result, the incidence of diabetes mellitus is also increasing. Since non-alcoholic steatohepatitis (NASH) is strongly associated with obesity and diabetes, it is likely that the incidence of NASH is increasing as well. Natural history studies show that up to 16% of patients with NASH may progress to cirrhosis and some of these patients will develop end-stage liver disease and/or possibly hepatocellular carcinoma, necessitating liver transplant. Currently, therapeutic options are limited. Standard practice has been to advocate weight loss and exercise, but supporting data are limited to small trials with varied results.
Orlistat, a reversible inhibitor of gastric and pancreatic lipases, blocks the absorption of approximately 30% of dietary triglycerides and was approved by the FDA in 1999 for the management of obesity. Data indicate that 38% of patients treated with orlistat and a low-fat diet for 1 year lose at least 5-10% of their baseline bodyweight. The effect of orlistat on NASH is unknown. Consequently, we designed a pilot trial of orlistat therapy for obese NASH patients. The aim of our study was to evaluate the efficacy of orlistat, given for 6 months to patients with obesity and histologically confirmed NASH.
