From NAFLD in clinical practice to answers from guidelines.

This review of the literature consists of three sections. First, papers concerning non-alcoholic fatty liver disease (NAFLD) awareness among the general population, general practitioners, and liver and non-liver specialists were retrieved and analyzed to highlight the perception of disease, verify knowledge of current recommendations, and identify the main difficulties experienced in clinical practice. Next, position papers and clinical practice guidelines issued by International and National Hepatological Scientific Societies were identified and critically assessed in order to pinpoint the areas of convergence/difference.

Clinical spectrum and therapy of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease is increasingly being diagnosed worldwide and considered to be the commonest liver disorder in Western countries. It comprises a disease spectrum ranging from simple steatosis (fatty liver) through non-alcoholic steatohepatitis (NASH) to fat with fibrosis and, ultimately, cirrhosis. Simple steatosis is largely benign and non-progressive, whereas NASH can lead to cirrhosis, liver failure and hepatocellular carcinoma.

Genetic and environmental susceptibility to non-alcoholic fatty liver disease.

While the majority of those with non-alcoholic fatty liver disease (NAFLD) will have simple hepatic steatosis, a minority will develop progressive steatohepatitis. Family studies and inter-ethnic variations in susceptibility suggest that genetic factors may be important in determining disease risk. Although no genetic associations with advanced NAFLD have been replicated in large studies, preliminary data suggest that polymorphisms in genes controlling lipid metabolism, pro-inflammatory cytokines, fibrotic mediators and oxidative stress may be associated with steatohepatitis and/or fibrosis.

Current and future therapeutic strategies in NAFLD.

Non alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and considered to be the commonest liver disorder in Western countries. It comprises a disease spectrum ranging from simple steatosis (fatty liver), through non-alcoholic steatohepatitis (NASH) to fat with fibrosis and ultimately cirrhosis. Simple steatosis is largely benign and non-progressive, whereas NASH, characterized by hepatocyte injury, inflammation and fibrosis can lead to cirrhosis, liver failure and hepatocellular carcinoma (HCC).

Genes and nonalcoholic fatty liver disease.

Whereas most individuals with nonalcoholic fatty liver disease (NAFLD) will have steatosis, only a minority will ever develop progressive disease. Family studies and interethnic variations in susceptibility suggest that genetic factors may be important in determining disease risk. Although no genetic associations with advanced NAFLD have been replicated in large studies, preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.

Non-alcoholic fatty liver disease: the mist gradually clears.

Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver disorder in the developed world affecting up to a third of individuals. It is closely associated with features of the metabolic syndrome, particularly obesity and diabetes. It can progress to cirrhosis, hepatocellular carcinoma and liver failure and is an increasing indication for transplantation.

Treatment of alcoholic liver disease.

Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with corticosteroids. Despite the importance of reactive oxygen species in the pathophysiology of ALD and ASH, antioxidants provide no benefit in the treatment of patients with ASH. Proinflammatory cytokines are important in the pathophysiology of ALD and might mediate most of the inflammatory aspects of these disorders.

Genetics of alcoholic liver disease and nonalcoholic fatty liver disease.

Although the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome have steatosis, only a minority ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of liver fibrosis. For ALD, the dose and pattern of alcohol intake, coffee intake, and dietary and other lifestyle factors leading to obesity are the most important environmental determinants of disease risk.

Genetic studies to identify hepatic fibrosis genes and SNPs in human populations.

Increasing evidence suggests that non-sex-linked genetic factors play a role in determining both susceptibility to, and progression of, liver fibrosis. The elucidation of these factors will have many potential benefits in the management of patients with chronic liver disease. A variety of approaches can be used to look for genetic factors playing a role in liver fibrosis.