Chronic Allograft Hepatitis C Infection in Liver Transplant Recipients: Fibrosis Progression in Sustained Virological Response and In Situ Hybridization Negative Allografts

Abstract

Purpose: Allograft hepatitis C (HCV) infection is a major problem among liver transplant (LT) recipients with chronic HCV with an accelerated course post-transplantation. Cirrhosis occurs in 6-30% within 5 years. Therapy is usually offered when liver biopsy demonstrates Ishak fibrosis >1 with ongoing necro-inflammatory activity, and stopped per individual institution protocols after confirming sustained virological response (SVR). The major objective of treatment of recurrent chronic hepatitis C after OLT is to prevent progression to cirrhosis and thereby prevent loss of the graft. The aim of our study is to examine the progression or regression of HCV related fibrosis in LT recipients with SVR. Methods: This is a retrospective chart review of the LT recipients treated for HCV allograft infection. LT recipients who had a substantial follow up after SVR and had corresponding liver biopsies at least annually, and without coexisting conditions that may cause fibrosis were only included in the study. We utilized Ishak scoring system for grading and staging, and to avoid operator variability only one liver pathologist scored all of the biopsies. Results: A total of 16 LT recipients matching the criteria were identified. Details are in the enclosed table. Clinically significant HCV activity in the allografts warranting treatment was noted at a median of 129 days from the time of LT. Histologically this corresponded to HCV hepatitis activity Ishak 6 and fibrosis Ishak 1 (medians). Interferon based regimens were utilized in conjunction with ribavirin, and in varying doses subject to recipient's tolerance. Allograft biopsies and HCV serologies were followed for a median of 880 days from the serological HCV clearance. At the last histological follow up, with SVR, 2 was the median Ishak fibrosis score. 37.5% of the allografts demonstrated an increase in Ishak fibrosis score by 2 median points (1-3) while 25% demonstrated an improvement by 1 point. The remaining 37.5 % demonstrated no change in fibrosis score. Conclusion: In our study cohort, in spite of HCV-RNA absence in serum and the allograft, fibrosis progressed to some degree in 37.5% of the allografts. Possible mechanisms to explain this phenomenon are persistent, low grade, graft cellular immune response to HCV, which may take years to disappear or the currently available tests are not sufficiently sensitive to detect low level HCV RNA leading to a low level persistent replication state in the graft or other yet unknown mechanisms. It remains to be verified if continuation of treatment beyond SVR for a certain period of time, which also needs to be defined, will result in better outcome.Table