A New FGF21 Analog for the Treatment of Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) describes a non–alcohol-induced cluster of conditions related to excessive fat stored in the liver. Defined as 5% or more hepatic fat content, NAFLD is prevalent, affecting ∼25% of the general population (1). Approximately 20% of individuals with NAFLD have a more aggressive form of the disease, termed nonalcoholic steatohepatitis (NASH), which is in addition characterized by liver inflammation and extensive scarring (cirrhosis) (1,2). NASH is a growing cause of liver cancer and a leading indication for liver transplantation (2). In addition, NAFLD and NASH are risk factors for chronic kidney disease (3), type 2 diabetes (4), and cardiovascular disease (5).Despite being serious afflictions, NAFLD and in particular NASH face two major headwinds. One, they are difficult to diagnose because they require liver biopsies for conclusive diagnosis. Two, there are currently no approved medications for treatment. Lifestyle intervention to reduce body weight is the primary strategy to manage the disease. However, while reducing caloric intake and increasing physical activity are obvious remedies, such lifestyle modification has very limited efficacy in the long run, with typically no more than 3–4% of weight loss after 4 years (6). With a quickly growing population of patients with NAFLD/NASH (2) and no approved therapies, there is an unmet yet steadily increasing medical need for safe and effective pharmacotherapy. Unfortunately, resembling the quest for the Holy Grail, the development of such a therapy seemed, as of today, a …