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The threat is aggravated by the fact that are currently no approved drugs for the treatment of non\u2010alcoholic steatohepatitis. In this paper, we review the main challenges to drug development in patients with non\u2010alcoholic steatohepatitis cirrhosis, and describe the opportunities brought by the advances in the understanding of the clinical and pathophysiological nuances of cirrhosis. The design of therapeutic regimens for non\u2010alcoholic steatohepatitis cirrhosis will vary according to the specific cirrhosis substage (compensated vs decompensated), and the specific mechanistic basis of therapy, targeted either at improving aetiology\u2010specific pathways and\/or at more general aetiology\u2010agnostic processes. The understanding of the probabilistic expectations for the whole range of potential outcomes, rooted at different mechanistic drivers at each specific substage, will be essential in order to choose adequate estimands and therapeutic strategies for clinical trials and individual patients with non\u2010alcoholic steatohepatitis cirrhosis. Finally, we provide a summary of the main pitfalls and uncertainties in the design of clinical trials for non\u2010alcoholic steatohepatitis cirrhosis and discuss potential biomarkers for use in trials and practice for these patients.<\/jats:p>","DOI":"10.1111\/liv.15013","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T16:29:33Z","timestamp":1625848173000},"page":"1999-2008","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Outcomes and potential surrogate markers for future clinical trials of non\u2010alcoholic steatohepatitis cirrhosis"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4357-8817","authenticated-orcid":false,"given":"Jes\u00fas","family":"Rivera\u2010Esteban","sequence":"first","affiliation":[{"name":"Liver Unit Department of Internal Medicine Vall d\u2019Hebron Hospital Universitari Vall d\u2019Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Armandi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Division of Gastroenterology and Hepatology A.O. 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