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Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10–20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases. Currently, diet and exercise are chiefly recommended to achieve significant weight loss and improve metabolic dysfunction in patients with NAFLD. However, weight loss remains to be an elusive goal for both clinical practitioners and NAFLD patients. To date, although there has not been any proven pharmacotherapy against NAFLD, numerous promising pipelines with good target engagement are under development. Moreover, given the global landmark phase 3 trials using obeticholic acid (a farnesoid X receptor agonist, REGENERATE trial) and elafibranor (a dual peroxisome proliferator-activated receptor α/δ agonist, RESOLVE-IT trial), the era of specific target therapies focusing on molecular and metabolic pathogenesis of NASH and fibrosis is near at hand. In this paper, we briefly cover the current and future therapeutic options in patients with NAFLD across the entire spectrum of diseases.
Figures and Tables
Table 1
Pivotal Phase II and III Clinical Trials for NASH Treatment
NASH, non-alcoholic steatohepatitis; FXR, farnesoid X receptor; PPAR, peroxisome proliferator-activated receptor; ASK1, apoptosis-signal regulating kinase 1; CCR, chemokine receptor; LXR, liver X receptor; SCD1, stearoyl CoA desaturase 1; LOXL, lysyl oxidase-like; FGF, fibroblast growth factor; ASBT, apical sodium dependent bile acid transporter; mTOR, mammalian target of rapamycin; GLP, glucagon-like peptide ; SGLT, sodium-glucose cotransporter; TH, thyroid hormone; VAP, vascular adhesion protein; ACC, acetyl-CoA carboxylase; Treg, regulator T cell; TLR, toll-like receptor.
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