Thiazolidinedione therapy for nonalcoholic steatohepatitis: Go, stop, or proceed with caution?
✍ Scribed by Stephen A. Harrison
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 75 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
he epidemic of obesity has been associated with a significant increase in nonalcoholic fatty liver disease (NAFLD). The pathogenesis of NAFLD in this setting is predicated on the premise that obesity-related insulin resistance is responsible for the development of hepatic steatosis. Our current understanding holds that in some patients, the increased free fatty acid (FFA) flux to the liver and decreased hepatic FFA oxidation results in lipotoxicity and progression to hepatocyte ballooning, lobular inflammation, and pericellular fibrosis-the histopathologic hallmarks of nonalcoholic steatohepatitis (NASH). To this end, investigators have predominantly focused on therapies that improve insulin resistance.
Weight loss has been recommended for many years, and there is data to show that this therapy is efficacious. Bariatric surgery improves the underlying metabolic dysfunction seen in the morbidly obese patient and improves histopathology in most studies. 1 In others, a modest weight loss (ϳ5%) improves insulin resistance while a weight loss of ϳ10% is associated with improvement in steatosis, ballooning, inflammation, and NAFLD activity score (NAS). 2 Unfortunately, the majority of patients with NAFLD are unable to lose weight and maintain their weight loss. Consequently, therapies aimed at improving insulin resistance either through augmenting or supplanting weight loss have been studied. The thiazolidinedione (TZD) class of insulin sensitizers has been the focus of attention for the past few years.
Rosiglitazone and pioglitazone, both TZDs, were approved in 1999 for the treatment of type II diabetes. They are peroxisome proliferator-activated receptor-␥ (PPAR-␥) ago-