Brief Overview of Non-Alcoholic Steatohepatitis (NASH) and Potential Future Treatments

Non-alcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat. It is a more severe and progressive form of nonalcoholic fatty liver disease (NAFLD). While NAFLD has a relatively benign prognosis, NASH has a risk of progression to fibrosis, cirrhosis, and rarely liver cancer. About a quarter of patients with NAFLD progress to NASH. The major risk factors for NASH are obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The prevalence of NASH is estimated at 1-5% of the population.  NASH is typically a silent disease in the early stages. It can take years or even decades for NASH to become serious enough to cause symptoms such as fatigue, weight loss, weakness, and right upper quadrant discomfort.

The gold standard for diagnosing NASH is liver biopsy, as this is the only test that can distinguish NASH from NAFLD. Considering the invasive nature of liver biopsy and the sheer number of NASH patients, routine use of biopsy will be financially challenging. Manufacturers and researchers are studying the accuracy and clinical utility of non-invasive diagnostic tools to more easily diagnose patients.

The treatment of NASH involves non-pharmacologic therapy including weight loss through exercise and dietary changes and a restriction in alcohol consumption. Currently, there are no FDA approved medications for NASH. However, efficacy has been demonstrated with pioglitazone and vitamin E, which are now used off-label.

With no medications approved for NASH, the pipeline is filled with potential agents exploring different mechanisms.  It is clear that manufacturers are in an exploratory phase of treating this condition.

For example, one of the early medications is obeticholic acid (OCA), a farnesoid X receptor inhibitor. This medication decreases liver bile acid build up, inflammation, and fibrosis of the liver. OCA is already approved for the orphan disease primary biliary colangitis (PBC), making NASH the second potential indication for OCA.

As new medications have been tested for NASH, defining the population that will benefit most from pharmacologic therapy has become increasingly important. Some clinical trials have a population consisting of all patients with NASH, while others have a population of patients with NASH and severe fibrosis. The FDA held a liver conference in 2013 and determined that the best patient population for NASH medications is those with NASH and a high fibrosis score. These patients are most at risk for cirrhosis and liver failure.

Treatments for NASH are expected to be a major focus once FDA approved products are on the market.  Start planning now for managing the expected new treatments for NASH.

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