One Year Follow-Up with Histology of HCV Liver Transplant Recipients who Received IV Interferon During the Anhepatic Phase of Transplant - A Controlled Pilot Study

Abstract

Purpose: Post transplant recurrent Hepatitis C continues to be a challenge after liver transplantation (LT). Primary aim of this pilot study was to determine the safety of IV Interferon (IFN) & Ribavirin (RBV) administered during anhepatic phase of LT & determine their effect on HCV RNA. Secondary aims included histologic response at 48 weeks post-transplant. Methods: 15 consecutive subjects undergoing LT for HCV cirrhosis were enrolled {10 cases (received IFN), 5- controls}. All cases received RBV 1000/1200 mg PO on call to OR, 5 MU IFN α-2b SQ at time of incision & 5 MU IFN α-2b IV at start of the anhepatic phase. Adverse events within 48 weeks post LT were recorded. HCV RNA levels were obtained pre-transplant, before & after anhepatic phase, at 12, 24, 48 & 96 hrs & at week 4, 8, 12, 24 & 48 post LT. IL28B status was recorded. All subjects underwent protocol liver biopsy at 48 weeks. Immunosuppression was protocol based and all but 2 received tacrolimus. Repeated Measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction. Results: All but 1 subject were male & mean age was 51 years. All had genotype 1 virus & mean MELD of study group was 18 + 6.2 (no significant difference between cases & controls). IL28B differed significantly between the 2 groups (cases - 5 CT, 2 CC, 1 TT, 1 not available; controls - 3 TT, 1 CT, 1 not available, p<0.05). We previously reported the regimen to be safe with easily manageable adverse events (n=3 subjects) and a trend for lower HCV RNA at week 4 among cases compared to controls (p >0.07; ACG 2012 # S132). There was no significant difference in Hgb, ANC, creatinine, ALT and length of stay post LT between the 2 groups. We now report follow-up 48 week data on our primary and secondary end-points. No additional adverse events were observed. The trend towards lower HCV RNA observed at week 4 among cases was lost at week 48 [HCV RNA was similar among cases and controls at 48 weeks post LT (5,866,398 + 9,441,240 vs. 5,216,657 + 4,968,923 respectively); p>0.05]. No significant difference was observed in histologic stage/grade at 48 weeks [data available in all but 2 subjects (1 case and 1 control)] between the 2 groups- all controls- stage 0 fibrosis; cases: Five- no fibrosis, One- stage 1 fibrosis, Three- stage 2 fibrosis. Conclusion: This pilot study suggests that IV IFN administered during the anhepatic phase of LT appears to be safe. There was a trend towards lower HCV RNA at week 4 post-LT among cases, although no significant virologic/ histologic effect was noted at 48 weeks. This limited data support further study of this novel approach for preventing recurrent post-LT HCV, possibly involving direct acting antiviral agents in select IL28B sub-groups.