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Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges
  1. Jean-François Dufour1,2,
  2. Cyrielle Caussy3,4,
  3. Rohit Loomba5
  1. 1Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
  2. 2University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
  3. 3Centre Hospitalier Lyon Sud, Endocrinologie Diabète et Nutrition, University Lyon 1, Hospices Civils de Lyon, Lyon, France
  4. 4NAFLD Research Center, University of California at San Diego, La Jolla, California, USA
  5. 5Division of Gastroenterology and Hepatology, Department of Medicine, NAFLD Research Center, University of California at San Diego, La Jolla, California, USA
  1. Correspondence to Professor Jean-François Dufour, Hepatology, Department of Clinical Research, University of Bern, Bern 3010, Switzerland; jean-francois.dufour{at}dbmr.unibe.ch

Abstract

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.

  • nonalcoholic steatohepatitis
  • hepatobiliary disease
  • liver
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Twitter @dufour_jf

  • Correction notice This article has been corrected since it published Online First. The title has been corrected.

  • Contributors All authors: drafting of the manuscript, critical revision of the manuscript, approved final submission.

  • Funding RL receives funding support from NIEHS (5P42ES010337), NCATS (5UL1TR001442), NIDDK (R01DK106419, P30DK120515) and DOD PRCRP (CA170674P2). J-FD receives funding from the Swiss National Foundation (310030_185219) and CC receives no relevant for this publication

  • Competing interests CC received consultant fees from NovoNordisk, AstraZeneca, Gilead. J-FD Advisory committees: Bayer, BMS, Falk, Genfit, Genkyotex, Gilead Science, HepaRegenix, Intercept, Eli Lilly, Merck, Novartis; Speaking and teaching: Bayer, BristolMyers Squibb, Intercept, Genfit, Gilead Science, Novartis. RL serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myer Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also cofounder of Liponexus.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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