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Semin Liver Dis 2020; 40(03): 298-306
DOI: 10.1055/s-0040-1708540
Review Article

The NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis

Jana Knorr
1   Department of Hepatology and Gastroenterology, Charité Campus Mitte and Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
,
Alexander Wree
1   Department of Hepatology and Gastroenterology, Charité Campus Mitte and Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
2   Department of Pediatric Gastroenterology, University of California, San Diego (UCSD), San Diego, California and Rady Children’s Hospital, San Diego, California
,
Frank Tacke
1   Department of Hepatology and Gastroenterology, Charité Campus Mitte and Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
,
Ariel E. Feldstein
2   Department of Pediatric Gastroenterology, University of California, San Diego (UCSD), San Diego, California and Rady Children’s Hospital, San Diego, California
› Author Affiliations
Funding This work was funded by NIH grants R01 DK113592 and U01 AA024206 to A.E.F., German Research Foundation (WR173/3–1 and SFB/TRR57 to A.W.), and German Cancer Aid (Deutsche Krebshilfe 70113000 to A.W.).
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Abstract

Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (ASH) are advanced forms of fatty liver diseases that are associated with a high morbidity and mortality worldwide. Patients with ASH or NASH are more susceptible to the progression of fibrosis and cirrhosis up to the development of hepatocellular carcinoma. Currently, there are limited medical therapies available. Accompanied by the asymptomatic disease progression, the demand for liver transplants is high. This review provides an overview about the growing evidence for a central role of NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex that acts as a central driver of inflammation via activation of caspase 1, maturation and release of pro-inflammatory cytokines including interleukin-1β, and trigger of inflammatory pyroptotic cell death in both NASH and ASH. We also discuss potential therapeutic approaches targeting NLRP3 inflammasome and related upstream and downstream pathways to develop prognostic biomarkers and medical treatments for both liver diseases.

Keywords

NLRP3 - nonalcoholic steatohepatitis - alcoholic steatohepatitis - inflammation - inflammasome


Publication History

Article published online:
11 June 2020

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