Liver fibrosis is the excessive expression and accumulation of extracellular 
matrix proteins in the liver. Fibrotic scarring occurs as the consequence of 
chronic injury and inflammation. While the successful treatment of hepatitis B 
and C reduced the burden of liver disease related to viral hepatitis, 
non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis 
(NASH) are nowadays the leading causes of hepatic fibrosis worldwide. Although 
basic research activities have significantly advanced our understanding of the 
molecular disease pathogenesis, the present therapeutic options for fibrosis are 
still limited. In advanced disease stages, liver transplantation often remains 
the only curative treatment. This highlights the necessity of preventive 
strategies to avoid complications of fibrosis, particularly cirrhosis, portal 
hypertension and liver cancer. Lifestyle modifications (weight loss, exercise, 
healthy diet) are the basis for prevention and treatment of NAFLD-associated 
fibrosis. In the present review, we discuss recent advances in antifibrotic 
prevention and therapy. In particular, we review the current concepts for 
antifibrotic drug candidates in the treatment of NAFLD and NASH. While some 
compounds aim at reverting pathogenic liver metabolism, an alternative approach 
is to disconnect the injury (e.g., NAFLD) from inflammation and/or fibrosis. 
Investigational drugs typically target metabolic pathways, insulin resistance, 
hepatocyte death, inflammatory cell recruitment or activation, the gut-liver 
axis, matrix expression or matrix turnover. While several promising drug 
candidates failed in phase 2 or 3 clinical trials (including elafibranor, 
emricasan and selonsertib), promising results with the farnesoid X receptor 
agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine 
receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an 
effective pharmacological therapy for liver fibrosis in the near future. 
Tackling NAFLD-associated fibrosis from different directions by combinatorial 
drug treatment and effective lifestyle changes hold the greatest prospects.