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.

Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice

“…In the present study, since food consumption was unaltered between the two mouse groups, the weight loss in the sitagliptin group was likely due to the inhibition of fat absorption from the gut. Trials of weight loss improve liver function and liver histology in NAFLD (28). The improvement of liver histology by sitagliptin may originate from both weight-independent and weight-dependent effects (29,30).…”

Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT2) Prevents Dietary Cholesterol-associated Steatosis by Enhancing Hepatic Triglyceride Mobilization

“…It is expected that as the prevalence of obesity and metabolic syndrome increases, NAFLD-associated diseases will be an increasing healthcare concern (8). Currently, there are no known effective treatments for NAFLD, although it is suggested that major changes in diet and exercise programs to reduce obesity could also diminish the severity and progression of NAFLD into non-alcoholic steatohepatitis and cirrhosis (2,3,(5)(6)(7)(8)(9).…”

“…We have found that inhibition of ACAT2 not only has the expected outcome of lowering hepatic CE but also limits hepatic triglyceride accumulation in several mouse models of dietary cholesterol-induced NAFLD. Based on the rapidly increasing prevalence of obesity in Western societies, an increase in obesity co-morbidities seems likely, particularly including diseases with earlier onset in obesity development such as NAFLD (2). The etiology of development of the NAFLD process is unclear, and currently, the treatment options for NAFLD are few (9).…”

“…accumulation in hepatocytes of patients with no history of chronic alcohol use (1,2). Lipid droplets consisting of neutral lipids (triglyceride and cholesteryl ester) accumulate within the hepatocyte and can contribute 5-10% or more of the total mass of the liver (3).…”

Factors Associated With Nonalcoholic Fatty Liver Disease in Obese Adolescents

“…Ultrasonographic fatty liver is defined when the accumulation of fat, mainly triglycerides, in hepatocytes exceeds 5% of the liver weight, and NAFLD refers to ultrasonographic fatty liver accompanied with liver function disruption [19].…”