Resolution of Liver Fibrosis: Basic Mechanisms and Clinical Relevance

Prakash Ramachandran, John P. Iredale, Jonathan A. Fallowfield*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract / Description of output

With evidence from a large number of animalmodels and clinical trials, it is now beyond debate that liver fibrosis and even cirrhosis are potentially reversible if the underlying cause can be successfully eliminated. However, in a significant proportion of patients cure of the underlying disease may not result in fibrosis regression or a significant reduction of the risk for hepatocellular carcinoma development. Understanding of the mechanistic pathways and regulatory factors that characterize matrix remodeling and architectural repair during fibrosis regression may provide therapeutic approaches to induce or accelerate regression as well as novel diagnostic tools. Recent seminal observations have determined that in resolving liver fibrosis a significant proportion of hepatic stellate cell-myofibroblasts (HSC-MFs) can revert to a near quiescent phenotype. Hepatic macrophages derived from inflammatory monocytes may contribute to fibrosis resolution through an in situ phenotypic switch mediated by phagocytosis. Emerging therapeutic approaches include deletion or inactivation of HSC-MFs, modulation of macrophage activity and autologous cell infusion therapies. Novel noninvasive diagnostic tests such as serum and imaging markers responsive to extracellular matrix degradation are being developed to evaluate the clinical efficacy of antifibrotic interventions.

Original languageEnglish
Pages (from-to)119-131
Number of pages13
JournalSeminars in liver disease
Volume35
Issue number2
DOIs
Publication statusPublished - 14 May 2015

Keywords / Materials (for Non-textual outputs)

  • matrix degradation
  • myofibroblast fate
  • proresolution macrophage
  • antifibrotic therapy
  • HEPATIC STELLATE CELLS
  • EXTRACELLULAR-MATRIX DEGRADATION
  • ENDOTHELIAL GROWTH-FACTOR
  • REGULATORY T-CELLS
  • NF-KAPPA-B
  • TISSUE INHIBITOR
  • STEM-CELLS
  • C VIRUS
  • NONALCOHOLIC STEATOHEPATITIS
  • CELLULAR SENESCENCE

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