Hepatic fibrosis: Concept to treatment

JOURNAL OF HEPATOLOGY

卷:62

Review

Trautwein, Christian¹  Friedman, Scott L.²  Schuppan, Detlef^3,4  Pinzani, Massimo⁵ 

[1] Rhein Westfal TH Aachen, Univ Hosp, Dept Internal Med 3, Aachen, Germany

[2] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA

[3] Univ Med Ctr, Inst Translat Immunol & Res Ctr Immunotherapy, Mainz, Germany

[4] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02115 USA

[5] UCL, Div Med, Inst Liver & Digest Hlth, London, England

关键词: Antifibrotic;    Fibrosis;    Hepatic stellate cells;    Liver;   

DOI  :  10.1016/j.jhep.2015.02.039

来源: Elsevier

【 摘 要 】

Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases. (C) 2015 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

【 授权许可】

Free