Hepatic Fibrosis, NASH

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in most of the Western world. The disease extends to nonalcoholic steatohepatitis (NASH), that can further progress to cirrhosis and is associated with an increased risk of cardiovascular mortality and type 2 diabetes mellitus. Cirrhosis due to NASH increases the risk of hepatocellular carcinoma and NASH contributes substantially to the population burden of hepatocellular cancer. The risk factors and comorbidities for NAFLD and NASH appear to be similar and include obesity, type 2 diabetes, and dyslipidemia. Further, increased age is associated with a worsened disease progression, prognosis and mortality. There is evidence suggesting male sex as a significant risk factor.

NASH generally presents as a silent disease with only a few symptoms. In the fatty liver, deposits of fat cause liver enlargement and inflammation. In early stages, patients feel well, but may discover upon routine serological testing that liver enzymes are elevated, thus prompting further examination. However, some patients may experience fatigue, weight loss, and weakness. These symptoms are more common in those who have advanced NASH and liver fibrosis. A patient with cirrhosis will likely experience fluid retention, muscle wasting, bleeding from the intestines, and liver failure.

 

The first therapeutic approach in NASH and liver fibrosis is to eradicate the underlying causes of the chronic inflammation, as far as possible. Obese patients should normalize their excessive food intake, and HBV and HCV infected patients should be treated with antivirals. Although partial reversal of liver fibrosis is observed in some cases, complete remodeling to cirrhosis can hardly be prevented. There are currently no approved therapies for NASH and liver fibrosis. The only option left in end stage liver disease is liver transplantation, although this is only available for a very limited group of patients.