Hepatic Injury in the Liver Allograft Biopsy Continues Despite Hepatitis C Viral Clearance with Interferon Treatment
Joshua P Cantor, George A Makar, Rajender Reddy, Emma E Furth. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Hepatitis C virus (HCV) recurrence following orthotopic liver transplantation (OLT) frequently results in progressive allograft injury, including cirrhosis and graft failure. Treatment of recurrent HCV after transplantation with interferon-based regimens has become widely accepted and has the potential to result in sustained virological response (SVR). The goal of this study is to determine what the histological outcome of SVR is in the transplanted liver.
Design: Fifty-five patients with recurrent HCV following liver transplantation and histological evidence of progressive hepatic fibrosis completed a standard course of interferon-based anti-viral therapy. Patients were categorized according to serologic response to therapy as measured by HCV RNA PCR. Progression of inflammatory activity and fibrosis was determined by histological comparison of biopsy material obtained before initiation of therapy to biopsies obtained during SVR. Biopsies were scored according to activity (0-3) and fibrosis (0-6). The presence and severity of acute and/or chronic rejection (ACR, CR) was recorded. The change in activity and fibrosis was measured over time.
Results: Thirty-one patients (56%) had undetectable serum levels of HCV RNA by PCR at the end of the therapy period, five of which serologically relapsed. Twenty-six patients (47%) achieved SVR. Twenty-four patients (44%) failed to demonstrate serologic viral clearance. Biopsy material for evaluation of progression of activity and fibrosis was available in 14/26 SVR patients (54%) and 16/24 nonresponders (67%). Time elapsed between pre-treatment and SVR biopsies ranged from 6-65 months (median 17) for the SVR group and from 3-37 months (median 8.5) for the nonresponder group. The Δactivity and Δfibrosis ranged from -0.04 to 0.036/month (median 0) and -0.033 to 0.333/month (median 0), respectively, for the SVR group and -0.3 to 0.091/month (median 0) and 0 to 0.667/month (median 0.06), respectively for the nonresponder group. There were 4 (29%) episodes of ACR in the SVR group and 3 (19%) in the nonresponder group. CR developed in 2 (14%) patients from the SVR group and 3 (19%) from the nonresponder group.
Conclusions: We conclude that hepatitic injury in the liver allograft persists despite SVR in response to interferon-based therapy. Additionally, there is no statistically significant difference in the Δactivity and in the Δfibrosis/time between biopsies from SVR and nonresponder liver allografts. Moreover, SVR may be associated with a mild increase in episodes of ACR.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 260, Monday Morning