An Endocrine Perspective of Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract

Endocrinologists are encountering patients with obesity-related complications such as metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) on a daily basis. Nonalcoholic fatty liver disease (NAFLD) is a liver condition characterized by insulin resistance, hepatic steatosis and frequently T2DM. This is now the most common chronic liver condition in adults and is present in the majority of obese subjects. Liver fat accumulation may range from simple steatosis to severe steatohepatitis with hepatocyte necroinflammation (or nonalcoholic steatohepatitis [NASH]). Although the natural history is incompletely understood, NAFLD may lead to serious medical consequences ranging from cirrhosis and hepatocellular carcinoma to earlier onset of T2DM and cardiovascular disease (CVD). The diagnosis of NAFLD may be challenging because signs and symptoms are frequently absent or nonspecific, and thus easily missed. Liver aminotransferases may be helpful if elevated, but most times are normal in the presence of the disease. Liver imaging may assist in the diagnosis (ultrasound or MRI and spectroscopy) but a definitive diagnosis of NASH still requires a liver biopsy. This may change in the near future as novel biomarkers become available. Treatment of NAFLD includes aggressive management of associated cardiovascular risk factors and many times control of T2DM. Pioglitazone and vitamin E appear promising for patients with NASH, although long-term studies are unavailable. In summary, this review hopes to address the common clinical dilemmas that endocrinologists face in the diagnosis and management of NAFLD and increase awareness of a potentially serious medical condition.

Keywords: diabetes; fatty liver; insulin resistance; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH).

Figure 1.

Dysfunctional, insulin-resistant adipose tissue is common in overweight and obese subjects and leads to excessive free fatty acids (FFAs) in the liver. This promotes triglyceride accumulation, hepatocyte lipotoxicity with necrosis, inflammation and eventual fibrosis. The metabolic consequences are dyslipidemia, hyperglycemia, hyperinsulinemia and subclinical inflammation, all leading to premature cardiovascular disease (CVD). NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.