Significant Hyperbilirubinemia with Sofosbuvir and Ribavirin-Based Antiviral Therapy in Post Liver Transplant Setting: An Unusual Etiology

Abstract

Introduction: Causes of hyperbilirubinemia in a patient on antiviral therapy with sofosbuvir and ribavirin include pre-existing or co-existing liver disease, ribavirin induced hemolysis, sofosbuvir induced hyperbilirubinemia and Gilbert's syndrome. We report a case of a post liver-transplant patient who developed hyperbilirubinemia after initiation of antiviral therapy with sofosbuvir and ribavirin. CaseSummary: A 52y male underwent live related liver transplant in August 2014. His daughter was the willing donor. He had twice failed therapy for chornic HCV with Interferon. Postoperative course was uneventful in both the recipient and the donor.In April 2015. He was treated with sofosbuvir and weight based ribavirin for active HCV GT3 infection. Liver stiffness was 3.0 kPa. Concomitant medications included tacrolimus 1 mg twice daily, mycophenolate 500 mg twice daily and amlodipine 2.5 mg daily. Tacrolimus level was 7.4 ng/ml. The patient showed progressive rise in bilirubin soon after initiation of this therapy with highest value of 10.6 mg/dl (direct 0.3 mg/dl and indirect 10.3 mg/dl) at week 16. Workup was inconclusive (table 1). He completed 6 months of therapy and had an SVR 12. The bilirubin level reached pre-treatment levels within 4 weeks after completion of the treatment. Discussion: Our patient demonstrated hyperbilirubinemia post-transplant on antiviral therapy with Sof/Riba. He had a peak Bilirubin of 10.6 mg/dl (direct/indirect 0.3/10.3) at week 16 with Pre and post antiviral treatment total bilirubin of 1.37 mg/dl and 1.63 mg/dl. This pattern is suggestive of underlying Gilbert's Syndrome in the graft. The patient had no jaundice during his antiviral treatments prior to transplant. We did not find any conclusive evidence of hyperbilirubinemia in the donor's record with pre donor hepatectomy, total bilirubin of 0.9 mg/dl (direct/indirect 0.29/ 0.61). We believe ribavirin induced hemolysis combined with bilirubin handling defect (Gilbert's Syndrome) in the graft lead to severe indirect hyperbilirubinemia during antiviral treatment. Conclusion: Severe indirect hyperbilirubinemia can occur with Sof/Riba containing antiviral therapy in liver transplant patient. Gilbert's syndrome in the donor should be an important consideration. This elevation in bilirubin level was asymptomatic and did not affect SVR12 in our case.