Non-Alcoholic Fatty Liver Disease (NAFLD) and its Recent Therapeutic Strategies

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a serious health issue globally. It includes a broad spectrum of alteration from simple steatosis to steatohepatitis and cirrhosis. Obesity and type-2 diabetes mellitus (T2DM) are the major factors that are associated with progression of NAFLD. The disease has been proven to have a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear; however some of many pathophysiological mechanisms that are involved in the development of NAFLD include fatty-acid accumulation in hepatic parenchyma, impaired mitochondrial metabolism, inflammation, oxidative stress, oxygen free radicals. Liver biopsy is the diagnostic gold-standard for NAFLD, but multiple non-invasive techniques like serological biomarkers and radiological techniques have established a new field for research. Since several inter-related pathways are involved in the pathological process, a single therapeutic agent is not helpful. Therefore, a combination therapy towards multiple targets could control the NAFLD. Various new targeted therapies includes apoptosis signal regulating kinase-1(ASK1) inhibitor, FXR (Farnesoid X receptor)-agonists, Caspase Inhibition, SCD-1(Stearoyl coenzyme A desaturase -1) enzyme inhibitors, SIRT1 (Sirtuin1) activator, CCR2 (chemokine receptor 2) and CCR5 (chemokine receptor 5) inhibitors, DPP-4 (Dipeptidyl peptidase-4) inhibitors and NOX (NADPH oxidase)-1/4 inhibitors that are currently under investigation. The treatment for patients with NAFLD is mainly based on loss of body weight and adjuvant management by using insulin sensitizer, anti-oxidants and reducing inflammation. The development of a healthy lifestyle and moderate exercise may be pillars for the treatment of NAFLD.