Current Options and Future Directions for NAFLD and NASH Treatment

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with CCR antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, CCR2/5 antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment.

Keywords: clinical trials; molecules; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; signaling pathway; treatment options.

Figure 1

The important molecules and signaling pathways are involved in the development of NAFLD and the progression of NASH. Abbreviations: ACC, acetyl-CoA carboxylase; Acox1, acyl-CoA oxidase 1; AKT, protein kinase B; AMPK, AMP-activated protein kinase; Fabp4, fatty acid-binding protein 4; FGF21, fibroblast growth factor 21; KLF15, Krüppel-like factors 15; GLP-1, glucagon-like peptide-1; NF-κB, nuclear factor (NF)-κB; PI3K, phosphoinositide 3-kinase; PPAR, peroxisome proliferator-activated receptor; TWIST2, twist-related protein 2; VCAM-1, vascular cell adhesion molecule 1.

Figure 2

Treatment options for NAFLD or NASH. The currently effective treatment options for NAFLD/NASH include lifestyle modification, bariatric surgery, and medicines. In addition, modification of gut microbiota by prebiotics, probiotics, or synbiotics shows promising effects.