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Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix

Razao Issa1, Xiaoying Zhou, Christothea M Constandinou

  • 1Division of Infection Inflammation and Repair, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.

Gastroenterology
|June 10, 2004
PubMed
Abstract

Insights

Recovery from advanced liver cirrhosis is possible, remodeling from micronodular to macronodular forms. This resolution is limited by tissue transglutaminase-mediated matrix cross-linking and insufficient hepatic stellate cell apoptosis.

Area of Science:

  • Hepatology
  • Cell Biology
  • Biochemistry

Background:

  • Liver fibrosis and cirrhosis involve excessive matrix protein secretion by hepatic stellate cells (HSCs).
  • Previously, cirrhosis was considered irreversible, prompting investigation into spontaneous recovery mechanisms.

Purpose of the Study:

  • To investigate the mechanisms that mediate and limit spontaneous recovery from a model of cirrhosis.
  • To understand the cellular and molecular changes during liver cirrhosis remodeling.

Main Methods:

  • Induced micronodular cirrhosis in rats using CCl(4) for 12 weeks.
  • Analyzed liver tissues for matrix degradation, MMP/TIMP expression, HSC apoptosis, tTg expression, and matrix cross-linking during 366 days of recovery.

Main Results:

  • Micronodular cirrhosis remodeled into macronodular cirrhosis over 366 days.
  • Decreased collagen-1 and TIMP mRNA, with active MMPs observed during fibrosis remodeling.
  • HSC apoptosis occurred at fibrotic septa margins; residual septa showed tTg-mediated cross-linking and reduced cellularity.

Conclusions:

  • Spontaneous recovery from advanced cirrhosis is achievable, involving remodeling to a macronodular form.
  • Recovery is limited by tTg-mediated matrix cross-linking and inadequate HSC apoptosis.

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