Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment

Abstract

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a significant correlation between hepatic steatosis, cardiovascular disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to develop hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. Therefore, training programmes in internal medicine, gastroenterology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and concomitant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging techniques and the readily available therapeutic options.

Figure 1

Pathogenesis of nonalcoholic steatohepatitis during insulin resistance. FFA is supplied to the liver through dietary intake, and lipolysis in adipocytes via chylomicron remnants. Transcription of SREBP-1c is chronically up-regulated resulting in DNL. Simultaneous inhibition of VLDL synthesis results in disruption of triglycerides export. The surplus of fatty acids is stored in triglycerides or metabolized via peroxisomal and mitochondrial oxidation. The excessive oxidation will lead to production of ROS and oxidative stress. This will trigger the inflammatory response and apoptosis as well activation of stellate cells.

Figure 2

Spectrum of a fatty liver measured by ¹H-magnetic resonance spectroscopy. The water peak is at 4.3 ppm. 1: Residual water partially suppressed; 2: Glycerol/phospholipids; 3: (-CH2-)_n of saturated fat.