Pharmacological management of nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) affects one-third of the population and two-thirds of patients with obesity or type 2 diabetes (T2DM). Its more aggressive form is known as nonalcoholic steatohepatitis (NASH) and is characterized by hepatocyte necrosis, inflammation and often fibrosis. The presence of fibrosis indicates a more aggressive course and may lead to cirrhosis. Premature mortality in NASH is related to both hepatic (cirrhosis and hepatocellular carcinoma) and extra-hepatic complications, largely cardiovascular disease (CVD). Many therapeutic agents have been tested, but still none approved specifically for NASH. Treatment of NAFLD includes aggressive management of diabetes and cardiovascular risk factors, although the role of controlling hyperglycemia per se in patients with T2DM and NASH remains unknown. Agents tested with some success in non-diabetic patients with NASH include pioglitazone, liraglutide, vitamin E and to a lesser degree, pentoxiphylline. In patients with T2DM and NASH only pioglitazone has shown to significantly improve liver histology, with only a handful of patients with diabetes having been studied with other modalities. This review focuses on available agents for NASH to assist clinicians in the management of these complex patients. Many novel compounds are being studied and will likely make combination therapy for NASH a reality in the future.

Treatment options to prevent diabetes in subjects with prediabetes: Efficacy, cost effectiveness and future outlook

“…The newest class of medications, which treat both type 2 diabetes and obesity, is the GLP-1 analogues. Increasing evidence suggests that these medications are efficacious not only at reducing weight, but also at improving the comorbidities of obesity, including cardiovascular disease, non-alcoholic steatohepatitis [35,36] and overall mortality [37–39]. Similar results to the most recent study, above, with liraglutide were demonstrated by this study group in the shorter-term.…”

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

“…Further NASH leads to liver cirrhosis and hepatocellular cancer (Brandi et al, ). On the other hand, all individual affected with lipid accumulation in liver does not develops steatosis and NASH, confirms the multiple pathogenic events involved in NAFLD mediated hepatic damage (Barb, Portillo‐Sanchez, & Cusi, ). Furthermore, research reports shows that not all patients with steatosis or NASH extend liver inflammation and hepatocellular injury has led to the guess that diverse pathogenic events lead primarily to hepatic steatosis and secondly to hepatic injury.…”

Glucagon like Peptide-1 Receptor Agonists for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: A Novel Therapeutic Option

“…Early studies in patients with T2DM suggested the potential benefit of GLP- 1RA from a reduction in liver enzymes 27. This reduction in plasma aminotransferases was also associated with a reduction in intrahepatic triglycerides proportional to the degree of weight loss28–30 or improvement in glycemic control 4.…”