Pharmacological management of nonalcoholic fatty liver disease.
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.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA; Division of Endocrinology, Diabetes and Metabolism at Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
Diana
D
Barb
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA; Division of Endocrinology, Diabetes and Metabolism at Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
Paola
P
Portillo-Sanchez
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA; Division of Endocrinology, Diabetes and Metabolism at Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA. Electronic address: Kenneth.Cusi@medicine.ufl.edu.
Kenneth
K
Cusi
D000975:Antioxidants / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology; D012307:Risk Factors
D000975:Antioxidants; D007004:Hypoglycemic Agents
Dipeptidyl peptidase 4 (DPP-4) inhibitors; Glucagon-like peptide-1 receptor agonists (GLP-1RA); Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Pioglitazone; Thiazolinediones