TY - JOUR
T1 - Therapeutic pipeline in nonalcoholic steatohepatitis
AU - Vuppalanchi, Raj
AU - Noureddin, Mazen
AU - Alkhouri, Naim
AU - Sanyal, Arun J.
N1 - Funding Information:
R.V. has received consulting fees for serving on the Data Safety Monitoring Boards for Covance, Enyio and Enanta; R.V. also received research grant support from Gilead Sciences, Zydus Discovery, Cara Therapeutics, Novo Nordisk, Eli Lilly, Astra Zeneca, Terns Pharmaceuticals and Intercept where his institution receives the funding; M.N. has been on the advisory board or a speaker for Allergan, Gilead, Intercept, Pfizer, Novartis, Blade, EchoSens North America, OWL, Simply Speaking and Abbott; M.N. has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire and Zydus; M.N. is a minor shareholder or has stocks in Anaetos and Viking. N.A. has received research funding from Albireo, Akero, Allergan, Boehringer Ingelheim, Bristol-Myers Squibb, Galmed, Genfit, Gilead, Intercept, Madrigal, MedImmune, Novartis, Novo Nordisk, Pfizer, Poxel and Zydus, and has acted as a speaker for AbbVie, Alexion, Allergan, Eisai, Exelixis, Gilead, Intercept and Salix and as a consultant for Allergan, Gilead and Intercept. A.J.S. is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect, Exalenz and Hemoshear; A.J.S. has served as a consultant to AstraZeneca, Nitto Denko, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, Fibrogen, Jannsen, Gilead, Lilly, Poxel, Artham, Cymabay, Boehringer Ingelheim, Novo Nordisk, Bird Rock Bio, Novartis, Pfizer, Jannsen and Genfit; A.J.S. has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Afimmune, ChemomAb, Nordic Bioscience and Bristol Myers Squibb; his institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, AstraZeneca, Mallinckrodt, Cumberland and Novartis; A.J.S. receives royalties from Elsevier and UptoDate.
Publisher Copyright:
© 2021, Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - Our understanding of nonalcoholic fatty liver disease pathophysiology continues to advance rapidly. Accordingly, the field has moved from describing the clinical phenotype through the presence of nonalcoholic steatohepatitis (NASH) and degree of fibrosis to deep phenotyping with a description of associated comorbidities, genetic polymorphisms and environmental influences that could be associated with disease progression. These insights have fuelled a robust therapeutic pipeline across a variety of new targets to resolve steatohepatitis or reverse fibrosis, or both. Additionally, some of these therapies have beneficial effects that extend beyond the liver, such as effects on glycaemic control, lipid profile and weight loss. In addition, emerging therapies for NASH cirrhosis would have to demonstrate either reversal of fibrosis with associated reduction in portal hypertension or at least delay the progression with eventual decrease in liver-related outcomes. For non-cirrhotic NASH, it is the expectation that reversal of fibrosis by one stage or resolution of NASH with no worsening in fibrosis will need to be accompanied by overall survival benefits. In this Review, we summarize NASH therapies that have progressed to phase II and beyond. We also discuss some of the potential clinical challenges with the use of these new therapies when approved.
AB - Our understanding of nonalcoholic fatty liver disease pathophysiology continues to advance rapidly. Accordingly, the field has moved from describing the clinical phenotype through the presence of nonalcoholic steatohepatitis (NASH) and degree of fibrosis to deep phenotyping with a description of associated comorbidities, genetic polymorphisms and environmental influences that could be associated with disease progression. These insights have fuelled a robust therapeutic pipeline across a variety of new targets to resolve steatohepatitis or reverse fibrosis, or both. Additionally, some of these therapies have beneficial effects that extend beyond the liver, such as effects on glycaemic control, lipid profile and weight loss. In addition, emerging therapies for NASH cirrhosis would have to demonstrate either reversal of fibrosis with associated reduction in portal hypertension or at least delay the progression with eventual decrease in liver-related outcomes. For non-cirrhotic NASH, it is the expectation that reversal of fibrosis by one stage or resolution of NASH with no worsening in fibrosis will need to be accompanied by overall survival benefits. In this Review, we summarize NASH therapies that have progressed to phase II and beyond. We also discuss some of the potential clinical challenges with the use of these new therapies when approved.
UR - http://www.scopus.com/inward/record.url?scp=85100955435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100955435&partnerID=8YFLogxK
U2 - 10.1038/s41575-020-00408-y
DO - 10.1038/s41575-020-00408-y
M3 - Review article
C2 - 33568794
AN - SCOPUS:85100955435
SN - 1759-5045
VL - 18
SP - 373
EP - 392
JO - Nature Reviews Gastroenterology and Hepatology
JF - Nature Reviews Gastroenterology and Hepatology
IS - 6
ER -