Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation
Open Access
- 23 September 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Liver Transplantation
- Vol. 11 (10), 1207-1213
- https://doi.org/10.1002/lt.20455
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. (Liver Transpl 2005;11:1207–1213.)Keywords
This publication has 36 references indexed in Scilit:
- Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-upTransplantation, 2004
- Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantationTransplantation, 2003
- Liver fibrosis – from bench to bedsideJournal of Hepatology, 2003
- The effects of increassing doses of ranitidine on intragastric pH in childrenGastroenterology, 2001
- Early Detection of Hepatitis C Allograft Reinfection after Orthotopic Liver Transplantation: A Molecular and Histologic StudyLaboratory Investigation, 2000
- Liver biopsy in hepatitis CJournal of Hepatology, 1999
- High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: Relationship with rejection episodesHepatology, 1999
- Histological and clinical outcome after liver transplantation for hepatitis CHepatology, 1997
- Liver stellate cells in chronic viral hepatitis: the effect of interferon therapyJournal of Hepatology, 1996
- Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitisHepatology, 1981