Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer

Abigale Lade, Luke A. Noon, Scott L. Friedman

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations


PURPOSE OF REVIEW: We review accumulating evidence that nonalcoholic steatohepatitis (NASH), a more advanced form of nonalcoholic fatty liver disease (NAFLD), predisposes patients to the risk of developing hepatocellular carcinoma (HCC), and we summarize recent advances in the elucidation of cancer-promoting pathways in NASH. We highlight the potential role of progenitor cells and hepatic stellate cells (HSCs) in promoting the early events that could culminate in cancer, as well as the emerging contribution of the gut-liver axis in promoting inflammation, senescence, and tumor growth in NASH and HCC. Finally, we review the role of bile acid receptors, vitamin D, and protective cellular pathways such as autophagy. RECENT FINDINGS: Studies have recently uncovered roles for gut microbiota, bile acid receptors and vitamin D in regulating the progression from NAFLD to HCC. Intriguing findings linking senescence and autophagy in hepatic stellate cells to HCC have also been discovered, as well as a link between dysregulated progenitor cell regulation and HCC. SUMMARY: NAFLD is the most common cause of chronic liver disease in the United States and Western Europe. The lack of definitive mechanisms underlying development of NASH among patients with NAFLD and its progression to HCC limit diagnosis and management, but new findings are paving the way for better biomarkers and therapies.

Original languageEnglish
Pages (from-to)100-107
Number of pages8
JournalCurrent Opinion in Oncology
Issue number1
StatePublished - Jan 2014


  • bile acids
  • hepatic stellate cells
  • hepatocellular carcinoma
  • microbiome
  • nonalcoholic fatty liver disease


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