The NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis

Seminars in Liver Disease - Tập 40 Số 03 - Trang 298-306 - 2020
Jana Knorr1, Alexander Wree1,2, Frank Tacke1, Ariel E. Feldstein2
1Department of Hepatology and Gastroenterology, Charité Campus Mitte and Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
2Department of Pediatric Gastroenterology, University of California, San Diego (UCSD), San Diego, California and Rady Children's Hospital, San Diego, California

Tóm tắt

AbstractNonalcoholic 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.

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