Original article—liver, pancreas, and biliary tract
Histologic Predictors of Fibrosis Progression in Liver Allografts in Patients With Hepatitis C Virus Infection

https://doi.org/10.1016/j.cgh.2009.10.034Get rights and content

Background & Aims

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.

Section snippets

Patient Population

This study was approved by the University of Pennsylvania institutional review board. The cohort was composed of all HCV-infected patients who underwent liver transplant at the University of Pennsylvania between 1999 and 2007. During this time, 996 total liver transplants were performed, of which 476 (48%) were in patients with chronic HCV. Twenty-three patients had 2 transplants between 1999 and 2007; disease progression in each transplanted liver was examined independently. Our

Results

The characteristics of our study population are shown in Table 1 and Supplementary Table 1. The same transplant team remained in place during the entire study period, and posttransplant patient and graft survival consistently were above the national average (data not shown). From the 476 transplants performed secondary to HCV cirrhosis, 52 (10.92%) rapid fibrosers and 61 (12.81%) slow fibrosers were identified. The mean follow-up time in years (±standard deviation [SD]) was 2.11 (±1.99) for the

Discussion

In summary, we have performed a large, single-institution, retrospective study of HCV patients posttransplant. We show that the rate of fibrosis on a population basis is constant throughout the posttransplant period and that the course of fibrosis is determined early posttransplant. Although several studies (incorporating patients transplanted from 1988–2002) have shown that the presence or absence of significant fibrosis on a biopsy at 1 year posttransplant was predictive of graft survival and

Acknowledgments

The authors gratefully acknowledge the assistance and contributions of Drs George Makar, Colleen Brensinger, Abraham Shaked, Kim Olthoff, Gerald Wertheim, Sriram Venneti, Rosalyn Diaz, and Helen Zhu.

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Conflicts of interest The authors disclose no conflicts.

Funding Supported by a National Institutes of Health grant (DK-058123 to R.G.W.) and Pathology and Laboratory Medicine intradepartmental grant support (E.E.F.).

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