Many interventions have been investigated for the treatment of
nonalcoholic steatohepatitis (NASH). This study aims to summarize all investigated options to date and review the use of specific endpoints at different stages of ongoing trials of noncirrhotic NASH treatments. Using a horizon scanning approach, evidence were identified including meta-analyses of randomized controlled trials (RCTs) in PubMed, EMBASE, Cochrane, and AMED (up to February 2020), recently published RCTs in PubMed (2015-April 2020), RCTs presented at conferences (AASL and EASL, 2015-2020), and ongoing RCTs in ClincalTrials.gov (2015-November 2020). We included 6 meta-analyses of RCTs, 30 published RCTs, 11 conference abstracts, and 62 ongoing RCTs. An evidence map was created to demonstrate the treatment effects of 49 therapeutic modalities for NASH. Only six interventions (6/49, 12.24%) met the histological
surrogate endpoints for potential conditional FDA approval.
Obeticholic acid is the only
therapy demonstrating positive benefits in ≥1-point improvement in
fibrosis with no worsening of NASH in a phase 3 trial. The other
therapies were all phase 2 studies. ≥1-point improvement in
fibrosis with no worsening of NASH was shown in patients treated with
cenicriviroc. NASH resolution with no worsening of
fibrosis was shown in patients treated with
liraglutide,
semaglutide and
resmetirom.
Lanifibranor achieved both surrogate histological endpoints. Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to
cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to
cirrhosis and adverse liver outcomes.