Hepatitis C virus (HCV) remains the most common indication for orthotopic liver transplantation (OLT) and universally reinfects the new liver graft; as a result, patients with HCV have poorer outcomes than patients undergoing OLT for non–HCV-related cirrhosis. Recently, new direct-acting antiviral (DAA) agents have been approved for genotype 1 HCV infections in combination with peginterferon/ribavirin (RBV).[2, 3] However, these therapies may be associated with morbidity and mortality when they are given to patients with advanced liver disease. We report a sustained response with an oral DAA/RBV combination without interferon in a 61-year-old male with HCV genotype 1b (interleukin-28B TT) who underwent OLT at our center for HCV-related cirrhosis.
He presented to our center for an OLT evaluation with a Model for End-Stage Liver Disease (MELD) score of 18 as well as ascites and encephalopathy, and interferon and RBV had previously failed in 1999. Once listed, he requested therapy with peginterferon/RBV and a DAA agent while he was awaiting OLT. Because of his ascites, encephalopathy, and MELD score, this was not offered. However, his HCV RNA viral level was found to be low at 887 IU/mL (Cobas TaqMan HCV assay), so telaprevir (TVR; 750 mg every 8 hours) and RBV (1200 mg daily) were initiated. At week 1 of therapy, his HCV RNA level was <43 IU/mL (target not detected). Because of gastrointestinal side effects at week 1 (nausea and diarrhea), he was converted to boceprevir (BOC; 800 mg every 8 hours) with RBV and underwent OLT 9 weeks after the initiation of therapy with a MELD score of 19. There were no additional episodes of decompensation, and he did not require transfusions, although an RBV dose reduction to 600 mg was required. Just before surgery, he took BOC (800 mg) as well as RBV (400 mg). Twenty-four weeks after OLT, he remained a sustained responder (Fig. 1).
Recent reports have demonstrated that a sustained virological response (SVR) can be achieved in HCV patients without interferon, although no studies to date have included patients with decompensated cirrhosis. However, to our knowledge, this represents the first successful cure of HCV in which DAA therapy without interferon was used to suppress the virus before OLT in a patient with decompensated liver disease in whom interferon was contraindicated. It should be emphasized that this case was unique because of the very low viral level and the more favorable genotype 1b infection. In addition, our patient was able to undergo OLT with a MELD score of 19, which is a level below the national median MELD score for deceased transplants in 2011. These factors allowed the combination of TVR and RBV followed by BOC with RBV to achieve viral suppression without the emergence of viral resistance. Because BOC may be administered for up to 44 weeks, our patient could have continued to receive BOC with RBV if no donor had been available, although it is unknown whether a breakthrough would have occurred with a longer duration of therapy. The vast majority of patients with genotype 1 infections who present for listing for OLT will have a viral level significantly higher than our patient's level (typically 104−106 IU/mL), and this level in our opinion would contraindicate our approach in this report because of the risk of treatment futility and resistance with nonstructural protein 3 protease inhibitors and RBV. However, more effective, all-oral DAA combinations with high barriers to resistance are currently being studied that can achieve high SVR rates in patients with high viral levels, and we believe the approach of DAA combinations without interferon may serve as a model for preventing reinfection of the liver graft and improving the survival of HCV-infected individuals who require OLT.
Paul Y. Kwo, M.D.1
A. Joseph Tector, M.D., Ph.D.2
Departments of 1Medicine and 2Transplant SurgeryIndiana University School of MedicineIndianapolis, IN