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New drugs for NAFLD: lessons from basic models to the clinic

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Abstract

The term nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of increasingly harmful conditions ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to liver fibrosis and end-stage cirrhosis. NAFLD is the currently most common form of chronic liver disease in both adults and children worldwide. As NAFLD evolves as a global pandemic alongside the still growing prevalence of metabolic syndrome, obesity, and diabetes, it is inevitable to develop effective counterstrategies. Over the last decades, great effort has been dedicated to the understanding of the pathogenesis of NAFLD. This includes the development of an array of models for NAFLD, ranging from advanced in vitro (primary cells, 3D cultures, biochip, spheroids, organoids) to in vivo rodent models (particularly in mice). Based on these approaches novel therapies have been proposed and subsequently evaluated for patients with advanced forms of NAFLD, in particular those with NASH and liver fibrosis or cirrhosis. In this review, we delineate the current understanding of disease pathophysiology and depict how novel therapeutic strategies aim to exploit these different mechanisms to ameliorate, treat, or stop progression of NASH. We also discuss obstacles and chances along the way from basic models to promising clinical treatment options.

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Funding

This work was funded by German Research Foundation (WR173/3-1, TA434/3-1, SFB/TRR57 and CRC1382 to AW and FT) and German Cancer Aid (Deutsche Krebshilfe 70113000 to AW).

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Authors and Affiliations

  1. Department of Medicine II, Nephrology/Rheumatology/Clinical Immunology, University Hospital RWTH Aachen, 52074, Aachen, Germany

    Katharina C. Reimer

  2. Department of Hepatology and Gastroenterology, Charité University Medical Center, Augustenburger Platz 1, 13353, Berlin, Germany

    Alexander Wree, Christoph Roderburg & Frank Tacke

Authors
  1. Katharina C. Reimer
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  2. Alexander Wree
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  3. Christoph Roderburg
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  4. Frank Tacke
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Correspondence to Frank Tacke.

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Conflict of interest

Dr. Tacke’s group has received research funding from Allergan, Inventiva, Bristol Myers Squibb, and Galapagos. The other authors state no conflict of interest.

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This article is a review of the literature and does not contain any studies with human participants or animals performed by any of the authors.

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Reimer, K.C., Wree, A., Roderburg, C. et al. New drugs for NAFLD: lessons from basic models to the clinic. Hepatol Int 14, 8–23 (2020). https://doi.org/10.1007/s12072-019-10001-4

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