Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis B (HBV), and chronic hepatitis C infection are the leading causes of chronic liver disease and hepatocellular carcinoma in the US. NAFLD, comprising non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), is a multi-system disease with hepatic and extrahepatic manifestations, such as type 2 diabetes mellitus and cardiovascular disease; it affects 30% of the adult population and at least 10% of children [1, 2]. NASH related liver transplantations are predicted to eclipse other indications over the next decade , and NASH has emerged as the dominant cause of hepatocellular carcinoma (HCC), the only cancer with rising incidence and third leading cause of cancer mortality . Deaths from HBV are declining, but models predict a two-fold increase in HCV-related deaths. Of the 18910 deaths due to HCC in 2010, at least half were attributed to HCV infection .
With the growing burden of end stage liver disease, the limitations of transplantation both in terms of cost and number of livers available, it is critical to increase the pace of development of safe and effective therapies to prevent and treat NASH, fibrosis and cirrhosis to reduce morbidity and mortality.
Interest in the development of therapeutic options to treat NASH, and to prevent or treat liver fibrosis and cirrhosis is high, with more than 40 pharmaceutical, biotech and diagnostic companies involved in exploring and testing therapeutic strategies . The drug development field is challenged by the complexity of the disease etiology and pathophysiology, natural course of disease and the resulting divergent strategies for therapeutic approaches.