Histologic predictors of fibrosis progression in liver allografts in patients with hepatitis C virus infection.
OBJECTIVE
Recurrent hepatitis C with ensuing fibrosis is the leading cause of liver allograft loss. We investigated whether histologic features in early posttransplant liver biopsies could predict the rate of fibrosis progression in this population.


METHODS
From 1999 to 2007 there were 476 liver transplants performed for hepatitis C at our center. We reviewed all available posttransplant biopsies for these patients; patients were categorized as rapid, intermediate, or slow fibrosers based on their METAVIR fibrosis score at 24 months. Stage F0 biopsies for rapid and slow fibrosers were analyzed histologically and immunohistochemically.


RESULTS
We identified 52 rapid fibrosers and 61 slow fibrosers in our cohort. There was a significant increase in the fibrosis progression rate in the group transplanted between 2003 and 2007 compared with between 1999 and 2002. The course of fibrosis progression was determined early in the posttransplant period and the rate was constant. Rapid fibrosers had more hepatocyte apoptosis than slow fibrosers (P = .001), but no difference in hepatitis activity on stage F0 biopsies. Rapid fibrosers also experienced more episodes of acute rejection after transplantation (P < .001). Cytokeratin 19 (CK19) and vimentin expression on F0 stage biopsies could distinguish rapid from slow fibrosers (CK19: area under the curve, 0.71; P = .0034; vimentin: P = .0219).


CONCLUSIONS
CK19, vimentin, and hepatocellular apoptosis are promising early markers of rapid fibrosis progression in patients transplanted for hepatitis C. The rate of fibrosis progression is established early in the posttransplant period; this initial rate dictates long-term outcome.
Meriden
Zina
Z
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Forde
Kimberly A
KA
Pasha
Theresa L
TL
Hui
Jia-Ji
JJ
Reddy
K Rajender
KR
Furth
Emma E
EE
Wells
Rebecca G
RG
D017209:Apoptosis; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000175:diagnosis* / Q000473:pathology*; D006526:Hepatitis C / Q000175:diagnosis* / Q000473:pathology*; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000032:analysis; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014184:Transplantation, Homologous / Q000473:pathology*; D017211:Treatment Failure; D014746:Vimentin / Q000032:analysis
D053539:Keratin-19; D014746:Vimentin