Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation

Samer Gawrieh, Bettina G. Papouchado, Lawrence J. Burgart, Shogo Kobayashi, Michael R. Charlton, Gregory James Gores

Research output: Contribution to journalArticle

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Abstract

Only a subset of hepatitis C virus (HCV)-infected patients develop progressive hepatic fibrosis after liver transplantation (LT). Hepatic stellate cell (HSC) activation is a pivotal step in hepatic fibrosis and precedes clinically apparent fibrosis. We determined whether early HSC activation, measured in 4-month protocol post-LT biopsies, is predictive of subsequent development of more histologically severe recurrence of HCV. Early (4 month) post-LT HSC activation, as measured by α-smooth muscle actin (α-SMA) staining, was determined in liver biopsies from recipients with severe (fibrosis score ≥ 2, n = 13) and with mild (fibrosis score of 0, n = 13) recurrence of HCV at one-year post-LT. Immunohistochemical staining for α-smooth muscle actin (α-SMA) was used to generate HSC activation scores (regional and total). Total HSC activation scores at 4 months were similar in patients with severe and mild HCV recurrence (3.9 ± 2.0 vs. 2.7 ± 2.2, P = 0.2). Regional HSC activation, assessed as parenchymal (zones 1, 2, and 3) or mesenchymal (portal tracts and fibrous septa), was different between the study groups, with higher mesenchymal scores predictive of progression. No patients in the mild recurrence group had detectable mesenchymal α-SMA staining vs. 46% (6/13) of patients with severe recurrence (P < 0.01). Mesenchymal activation of HSC had a specificity and positive predictive value of 100% for development of progressive fibrosis in liver allografts of patients with hepatitis C. In conclusion, early activation of mesenchymal HSCs is a marker for progressive fibrosis in patients with hepatitis C post-LT and may help select patients who would benefit from HCV or HSC-targeted therapy.

Original languageEnglish (US)
Pages (from-to)1207-1213
Number of pages7
JournalLiver Transplantation
Volume11
Issue number10
DOIs
StatePublished - Oct 2005

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Hepatic Stellate Cells
Hepatitis C
Liver Transplantation
Recurrence
Fibrosis
Hepacivirus
Staining and Labeling
Smooth Muscle
Actins
Liver
Biopsy
Cell- and Tissue-Based Therapy
Liver Cirrhosis
Allografts

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation. / Gawrieh, Samer; Papouchado, Bettina G.; Burgart, Lawrence J.; Kobayashi, Shogo; Charlton, Michael R.; Gores, Gregory James.

In: Liver Transplantation, Vol. 11, No. 10, 10.2005, p. 1207-1213.

Research output: Contribution to journalArticle

Gawrieh, Samer ; Papouchado, Bettina G. ; Burgart, Lawrence J. ; Kobayashi, Shogo ; Charlton, Michael R. ; Gores, Gregory James. / Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation. In: Liver Transplantation. 2005 ; Vol. 11, No. 10. pp. 1207-1213.
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