Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

Petra Hirsova, Adebowale O. Bamidele, Haiguang Wang, Davide Povero, Xavier S. Revelo

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. A significant proportion of patients with NAFLD develop a progressive inflammatory condition termed nonalcoholic steatohepatitis (NASH), which may eventually advance to cirrhosis and hepatocellular carcinoma (HCC). NASH is characterized by steatosis, hepatocyte ballooning, and lobular inflammation. Heightened immune cell infiltration is a hallmark of NASH, yet the mechanisms whereby hepatic inflammation occurs in NASH and how it contributes to disease initiation and progression remain incompletely understood. Emerging evidence indicates that intrahepatic T cell immune mechanisms play an integral role in the pathogenesis of NASH and its transition to HCC. In this review, we summarize the current knowledge regarding the T cell-mediated mechanisms of inflammation in NASH. We highlight recent preclinical and human studies implicating various subsets of conventional and innate-like T cells in the onset and progression of NASH and HCC. Finally, we discuss the potential therapeutic strategies targeting T cell-mediated responses for the treatment of NASH.

Original languageEnglish (US)
Article number760860
JournalFrontiers in Endocrinology
StatePublished - Oct 28 2021

Bibliographical note

Funding Information:
PH received support from the AASLD Foundation (Pinnacle Research Award) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under the Award Numbers P30DK084567 and R01DK130884. AB is supported by the NIH grant K01DK124358 and the Mayo Clinic Center for Biomedical Discovery Career Development Award. DP received support from the NIH grants P30DK084567 and 5T32DK007352-42. XR is supported by NIH grants R01DK122056 and R01HL155993, and the American Association of Immunologists Careers in Immunology Award.

Publisher Copyright:
© Copyright © 2021 Hirsova, Bamidele, Wang, Povero and Revelo.


  • CD4/CD8 lymphocytes
  • HCC
  • Inflammation
  • NASH
  • T cells


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