Non-alcoholic fatty liver disease is comprised of either simple steatosis (non-alcoholic fatty liver) or a more advanced inflammatory and fibrogenic stage (non-alcoholic steatohepatitis [NASH]). NASH affects a growing proportion of the global adult and pediatric population, leading to rising rates of liver fibrosis and hepatocellular carcinoma. NASH is a multifactorial disease that is part of a systemic metabolic disorder. Here, we provide an overview of the metabolic underpinnings of NASH pathogenesis and established drivers of inflammation and fibrosis. Clarification of underlying fibrogenic and inflammatory mechanisms will advance the development of novel treatment strategies as there are no approved therapies at present. We discuss emerging experimental approaches and potential novel investigational strategies derived from animal models including the inflammasome, epigenetic reprogramming, Hippo signaling, Notch signaling, engineered T cells to remove fibrogenic HSCs, and HSC-specific targeting therapies. Recently completed and ongoing clinical trials and antifibrotics are discussed, illuminating the growing expectation that one or more therapies will yield clinical benefit in NASH in the coming years.

Original languageEnglish
Pages (from-to)11-31
Number of pages21
JournalJournal of Internal Medicine
Issue number1
StatePublished - Jan 2022


  • fibrosis
  • insulin resistance
  • lipotoxicity
  • liver cancer
  • non-alcoholic fatty liver disease
  • non-alcoholic steatohepatitis


Dive into the research topics of 'Inflammatory and fibrotic mechanisms in NAFLD—Implications for new treatment strategies'. Together they form a unique fingerprint.

Cite this