Safety and Efficacy of New Daa Regimens in Kidney and Liver Transplant Recipients with Hepatitis C: Interval Results from the HCV-Target Study

POSTER PRESENTATIONS Results: If the current treatment paradigm continues (26,860 patients treated annually), the number of incident HCC cases is projected at 5,840 in 2030, a decrease of 75% as compared to 2014 (23,030 incident HCC cases). Annual HCC related deaths decline 55% from 24,890 in 2014 to 10,680 in 2030. Total viremic HCV infections decline to 271,000 in 2030 as compared to 1,014,000 in 2014 (75% decrease), largely due to mortality. Under scenario 1, incident HCC cases in 2014 were estimated at 25 070 (10% increase from base) while incident HCC in 2030 was estimated at 12,050 (105% increase from base). HCC related mortality was estimated at 25,690 deaths in 2014 (5% increase from base) and 15,980 deaths in 2030 (115% increase from base). Viremic HCV infections in 2014 are estimated at 1,223,000, an increase of 20% from the base case. Under scenario 2, incident HCC cases in 2030 were estimated at 3,340, a decrease of 45% as compared to the base case, while incident HCC deaths were estimated at 8,610, a decrease of 20% from the base. Viremic HCV infections in 2030 were estimated at 206,700, a decrease of 25% from the base case. Conclusions: The base case results show a substantial burden of incident HCC and related deaths attributable to HCV, while results from scenario 1 indicate that current HCC burden would be substantially greater if antiviral therapy had not been implemented in 1992. Treatments with greater efficacy (scenario 2) can reduce HCC-related disease burden in Japan, with marked declines in incident HCC and deaths by 2030. SAT-188 AN INTEGRATED SAFETY AND EFFICACY ANALYSIS OF SOFOSBUVIRBASED REGIMENS IN PATIENTS WITH HEREDITARY BLEEDING DISORDERS K.R. Reddy1, C. Stedman2, K. Workowski3, J.C. Yang4, L.M. Stamm4, M. Lin4, D.M. Brainard4, J.G. McHutchison4, G.P. Balba5, E.J. Gane6, C. Walsh7. 1Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, United States; 2Christchurch Clinical Studies Trust, Christchurch, New Zealand; 3Emory University, Atlanta; 4Gilead Sciences, Inc, Foster City; 5Georgetown University Hospital, Washington, DC, United States; 6Auckland Clinical Studies, Auckland, New Zealand; 7 Mount Sinai Hospital, New York, United States E-mail: [email protected] Background and Aims: Patients with hereditary bleeding disorders have been included in Phase 2 and 3 clinical trials of sofosbuvir (SOF) and ledipasvir/sofosbuvir (LDV/SOF) as well as in a dedicated study (n = 120) in this patient population. This integrated analysis evaluates the safety and efficacy of SOF-based regimens in HCV-infected patients with hereditary bleeding disorders. Methods: HCV-infected patients with a medical history of a hereditary bleeding disorder who participated in a SOF or LDV/SOF Phase 2 or 3 study were included in this pooled analysis. Medical history term(s) used to identify patients with bleeding disorders included variations of Hemophilia A or B, Von Willebrand’s Disease, Factor Deficiencies, or conditions associated with hemophilia such as hemophilic arthropathy. Results: A total of 184 patients (74% GT1, 9% GT2, 14% GT3, and 1% GT4) with bleeding disorders were identified across 14 studies. The majority were male (93%), Caucasian (81%), IL28B non-CC (69%), and without cirrhosis (72%). Hemophilia A (65%) and B (25%) were the most common bleeding disorders. SVR12 results are shown in the Table by treatment regimen and genotype. The most frequently reported adverse events (>10%) were headache, fatigue, and diarrhea; majority were mild or moderate in severity. One patient (<1%) discontinued LDV/SOF due to an adverse event and 11 patients (6%) experienced a serious adverse event. Hemarthrosis, muscle hemorrhage, and epistaxis were the only hemorrhagic events that occurred in >1 patient. Grade 3 or 4 laboratory abnormalities were infrequent with anemia and hyperbilirubinemia the most frequent Grade 3 laboratory abnormality consistent with RBV administration.

Conclusions: SOF + RBV and LDV/SOF ± RBV led to high rates of SVR in genotype 1–4 HCV infected patients with bleeding disorders. SOF-based regimens were safe and well tolerated with no new toxicity specific to patients with bleeding disorders emerging. SAT-189 SAFETY AND EFFICACY OF NEW DAA REGIMENS IN KIDNEY AND LIVER TRANSPLANT RECIPIENTS WITH HEPATITIS C: INTERVAL RESULTS FROM THE HCV-TARGET STUDY K.R. Reddy1, M.S. Sulkowski2, M. Hassan3, J. Levitsky4, J. O’Leary5, R.S. Brown6, E.C. Verna6, A. Kuo7, R.T. Stravitz8, J.K. Lim9, V. Saxena10, D.R. Nelson11, P. Hayashi12, M. Vainorius12, M.W. Fried12, N. Terrault10. 1 University of Pennsylvania, Philadelphia; 2Johns Hopkins University, Baltimore; 3University of Minnesota, Minneapolis; 4Northwestern University Feinberg School of Medicine, Chicago; 5Baylor University Medical Center, Dallas; 6Columbia University, New York; 7University of California, San Diego; 8Virigina Commonwealth University, Richmond; 9 Yale University School of Medicine, New Haven; 10University of California, San Francisco; 11University of Florida, Gainesville; 12 University of North Carolina, Chapel Hill, United States E-mail: [email protected] Background and Aims: Chronic HCV therapy with DAAs is associated with high response rates and is well tolerated. However data in the solid organ transplant population are limited. We evaluated the safety and effectiveness of current treatment regimens in posttransplant patients enrolled in HCV-TARGET, an international consortium of academic and community medical centers. Methods: Demographic, clinical, adverse events and virological data were collected throughout treatment and post-treatment follow-up in solid organ transplant recipients treated between October 2014 and October 2015. Results: 374 patients were evaluated (Kidney (KT) only = 50, Liver (LT) only = 290, combined Liver/Kidney (kidney/LT) = 34). Majority were 40–64 years old (68%), 64% male, and 57% were non-cirrhotic, 207 (55%) had failed prior antiviral therapy. Among those with cirrhosis (n = 161), more than half (n = 86) had prior history of decompensating events. Majority was G1 (93% with 57% G1a, 27% G1b, 9% 1 indeterminate). (Table). The immunosuppression included Tacrolimus (TAC) 274 (73%), Cyclosporine (CSA) 58 (16%), Everolimus/ Sirolimus 39 (1%), and 184 (49%) additionally were on Mycophenolate Mofetil (MMF)/Mycophenolic acid (MPA). 350/374 (94%) were treated with Ledipasvir/ Sofosbuvir (LDV/SOF) +/−RBV;(15 (4%) patients) with Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (Omb/Par/r/Das) with or without Ribavirin and (9(2%) patients), with Daclatasvir/ Sofosbuvir containing regimens. SVR rates were 100% in KT, and 93% in LT and 88% combined kidney/LT (Table). At least one AE was reported in 159/230 (69%) of patients and most were mild. Anemia events were only observed in patients treated with RBV containing regimens and occurred in 5 patients. A total of 14 patients (13 in OLT group and 1 in OLT/KT group) in the safety cohort received EPO, and 4 (all in OLT only group) received a blood transfusion. There was one

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episode of acute kidney transplant rejection (LDV/SOF) in kidney transplant only group. 3 patients reported SAE (OLT group) one patient have developed acute renal failure (LDV/SOF +/− RBV). A total of 26 patients have an SAE reported to date and there was one death. Conclusions: Liver alone, liver/kidney, and kidney alone transplant recipients with chronic HCV can be effectively and safely treated with currently available all oral DAA regimens. Most patients were treated with LDV/SOF ± RBV and achieved high SVR. Graft rejection related to therapy was not observed. SAT-190 RENAL FUNCTION DECLINE IS FREQUENT IN PATIENTS UNDERGOING HEPATITIS C TREATMENT POST KIDNEY TRANSPLANT K.R. Bhamidimarri1, P. Martin1, C. Levy1, D. Roth1. 1University of MiamiMiller School of Medicine, Miami, United States E-mail: [email protected] Background and Aims: DAA therapy is now feasible post kidney transplantation (KT) and has also allowed transplantation of HCV positive organs in HCV positive recipients. However there are no reports of treatment experience in patients post KT to date with the

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new DAAs. Aim: To describe our experience of HCV treatment in KT recipients who received HCV positive grafts. Methods: Consecutive HCV RNA positive patients on the transplant waiting list who consented to receive a kidney from a HCV (+) donor were included in the analysis. Induction immunosuppression (IS) included thymoglobulin and simulect followed by maintenance IS with tacrolimus and mycophenolate mofetil. At approximately 3 months post-transplant, HCV treatment was initiated with sofosbuvir/ledipasvirand/or ribavirin for 12 weeks. Labaratory parameters were closely monitored during treatment. Results: HCV treatment was well tolerated but patients receiving ribavirin had variable grades of anemia which required ribavirin dose adjustment or discontinuation. We presented our SVR data in AASLD 2015 in this group which is around 92%. Interestingly, renal function decline was frequent in the KT recipients. Two thirds of the patients (10/15) required tacrolimus dose adjustments of which 9 patients (60%) required augmentation of the dose (range 12%>100%) and 1 patient required decreased dose. Three patients (20%) had biopsy proven antibody mediated rejection after the achievement of aviremia during treatment. Renal function improved with close titration and monitoring of immunosuppression.

Journal of Hepatology 2016 vol. 64 | S631–S832