How I treat hepatitis C virus infection in patients with hematologic malignancies

Blood

Volumn 128, Issue 11, 2016, Pages 1449-1457

  Torres, Harrys A ^a   McDonald, George B ^b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; BILIRUBIN; BORTEZOMIB; CISPLATIN; CYCLOPHOSPHAMIDE; DASABUVIR; DOXORUBICIN; FLUDARABINE; FLUOROURACIL; HEPATITIS C ANTIBODY; LEDIPASVIR; LENALIDOMIDE; MELPHALAN; MYCOPHENOLATE MOFETIL; OMBITASVIR; PACLITAXEL; PARITAPREVIR; PREDNISONE; RIBAVIRIN; RITONAVIR; RITUXIMAB; SOFOSBUVIR; SORAFENIB; TACROLIMUS; VINCRISTINE;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL THERAPY; ARTICLE; ASCITES; BILIRUBIN BLOOD LEVEL; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CHOLESTATIC HEPATITIS; CLINICAL ARTICLE; CONFUSION; CORD BLOOD STEM CELL TRANSPLANTATION; DIARRHEA; ENDOSCOPIC BIOPSY; FEMALE; GRAFT VERSUS HOST REACTION; HEMATOLOGIC MALIGNANCY; HEPATITIS C; HEPATITIS C VIRUS GENOTYPE 1; HLA MATCHING; HUMAN; HUMAN TISSUE; JAUNDICE; LEUKEMIA REMISSION; LIVER BIOPSY; LIVER FIBROSIS; LIVER FUNCTION TEST; LIVER NODULE; MALE; MIDDLE AGED; NAUSEA; NEUROTOXICITY; NONHUMAN; PERIPHERAL NEUROPATHY; POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; REDUCED INTENSITY CONDITIONING; SIDE EFFECT; SPLENIC MARGINAL ZONE LYMPHOMA; T CELL LYMPHOMA; TREATMENT DURATION; TREATMENT PLANNING; VOMITING; CASE REPORT; COMBINATION DRUG THERAPY; COMPLICATION; DRUG EFFECTS; HEMATOLOGIC DISEASE; HEPACIVIRUS; HEPATITIS C, CHRONIC; PATHOLOGY;

ADULT; ANTIVIRAL AGENTS; DRUG THERAPY, COMBINATION; FEMALE; HEMATOLOGIC NEOPLASMS; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; MALE; MIDDLE AGED;

EID: 84988432754     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2016-05-718643     Document Type: Article

References (99)

1. Smith BD, Morgan RL, Beckett GA, et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965 [published correction appears in MMWR Recomm Rep. 2012;61(43):886]. MMWR Recomm Rep. 2012;61(RR-4):1-32.
2. Fujii Y, Kaku K, Tanaka M, Yosizaki M, Kaneko T, Matumoto N. Hepatitis C virus infection in patients with leukemia. Am J Hematol. 1994;46(4): 278-282.
3. Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology. 1999; 46(29):2925-2930.
4. Faggioli P, De Paschale M, Tocci A, et al. Acute hepatic toxicity during cyclic chemotherapy in non Hodgkin's lymphoma. Haematologica. 1997; 82(1):38-42.
5. Vento S, Cainelli F, Longhi MS. Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy: an unresolved issue. Lancet Oncol. 2002;3(6):333-340.
6. Iqbal T, Mahale P, Turturro F, Kyvernitakis A, Torres HA. Prevalence and association of hepatitis C virus infection with different types of lymphoma. Int J Cancer. 2016;138(4):1035-1037.
7. Allison RD, Tong X, Moorman AC, et al; Chronic Hepatitis Cohort Study (CHeCS) Investigators. Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006-2010. J Hepatol. 2015;63(4): 822-828.
8. Nieters A, Kallinowski B, Brennan P, et al. Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology. 2006;131(6): 1879-1886.
9. Torres HA, Mahale P, Blechacz B, et al. Effect of hepatitis C virus infection in patients with cancer: addressing a neglected population. J Natl Compr Canc Netw. 2015;13(1):41-50.
10. Borchardt RA, Torres HA. Challenges in managing hepatitis C virus infection in cancer patients. World J Gastroenterol. 2014;20(11): 2771-2776.
11. Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol. 2012;9(3):156-166.
12. American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). HCV guidance: recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org. Accessed July 11, 2016.
13. Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374.
14. Hartridge-Lambert SK, Stein EM, Markowitz AJ, Portlock CS. Hepatitis C and non-Hodgkin lymphoma: the clinical perspective. Hepatology. 2012;55(2):634-641.
15. Torres HA, Mahale P. Most patients with HCVassociated lymphoma present with mild liver disease: a call to revise antiviral treatment prioritization. Liver Int. 2015;35(6):1661-1664.
16. Kawamura Y, Ikeda K, Arase Y, et al. Viral elimination reduces incidence of malignant lymphoma in patients with hepatitis C. Am J Med. 2007;120(12):1034-1041.
17. National Comprehensive Cancer Network (NCCN). Splenic Marginal Zone Lymphoma. Version 1, 2016.
18. Economides MP, Mahale P, Turturro F, et al. Development of non-Hodgkin lymphoma as a second primary cancer in hepatitis C virus-infected patients with a different primary malignancy [published online ahead of print June 27, 2016]. Leuk Lymphoma. doi:10.1080/10428194.2016.1196817.
19. Kyvernitakis A, Mahale P, Popat UR, et al. Hepatitis C virus infection in patients undergoing hematopoietic cell transplantation in the era of direct-acting antiviral agents. Biol Blood Marrow Transplant. 2016;22(4):717-722.
20. Radkowski M, Gallegos-Orozco JF, Jablonska J, et al. Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology. 2005;41(1):106-114.
21. Mahale P, Okhuysen PC, Torres HA. Does chemotherapy cause viral relapse in cancer patients with hepatitis C infection successfully treated with antivirals? Clin Gastroenterol Hepatol. 2014;12(6):1051-1054.
22. Peffault de Latour R, Lévy V, Asselah T, et al. Long-term outcome of hepatitis C infection after bone marrow transplantation. Blood. 2004;103(5): 1618-1624.
23. Torres HA, Chong PP, De Lima M, et al. Hepatitis C virus infection among hematopoietic cell transplant donors and recipients: American Society for Blood and Marrow Transplantation Task Force Recommendations. Biol Blood Marrow Transplant. 2015;21(11):1870-1882.
24. Mallet V, van Bömmel F, Doerig C, et al. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). Lancet Infect Dis. 2016;16(5):606-617.
25. Weinbaum CM, Williams I, Mast EE, et al; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR08):1-20.
26. Mahale P, Kontoyiannis DP, Chemaly RF, et al. Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients. J Hepatol. 2012;57(6):1177-1185.
27. Sakai M, Strasser SI, Shulman HM, McDonald SJ, Schoch HG, McDonald GB. Severe hepatocellular injury after hematopoietic cell transplant: incidence, etiology and outcome. Bone Marrow Transplant. 2009;44(7):441-447.
28. McGovern BH, Birch CE, Bowen MJ, et al. Improving the diagnosis of acute hepatitis C virus infection with expanded viral load criteria. Clin Infect Dis. 2009;49(7):1051-1060.
29. Evans AT, Loeb KR, Shulman HM, et al. Fibrosing cholestatic hepatitis C after hematopoietic cell transplantation: report of 3 fatal cases. Am J Surg Pathol. 2015;39(2):212-220.
30. Vento S, Cainelli F, Mirandola F, et al. Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus. Lancet. 1996; 347(8994):92-93.
31. Mahale P, Thomas SK, Kyvernitakis A, Torres HA. Management of multiple myeloma complicated by hepatitis C virus reactivation: the role of new antiviral therapy. Open Forum Infect Dis. 2015;3(1):ofv211.
32. Varma A, Saliba RM, Torres HA, et al. Outcomes in hepatitis C virus seropositive lymphoma and myeloma patients after autologous stem cell transplantation. Bone Marrow Transplant. 2016; 51(7):999-1001.
33. Oliver NT, Nieto YL, Blechacz B, Anderlini P, Ariza-Heredia E, Torres HA. Severe hepatitis C reactivation as an early complication of hematopoietic cell transplantation [published online ahead of print July 18, 2016]. Bone Marrow Transplant. 2016.
34. van Schaik RH. CYP450 pharmacogenetics for personalizing cancer therapy. Drug Resist Updat. 2008;11(3):77-98.
35. Mahale P, Kaseb AO, Hassan MM, Torres HA. Hepatocellular carcinoma as a second primary cancer in patients with chronic hepatitis C virus infection. Dig Liver Dis. 2015;47(4):348-349.
36. Miyatake H, Kobayashi Y, Iwasaki Y, et al. Effect of previous interferon treatment on outcome after curative treatment for hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci. 2012; 57(4):1092-1101.
37. Breitenstein S, Dimitroulis D, Petrowsky H, Puhan MA, Müllhaupt B, Clavien PA. Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg. 2009;96(9):975-981.
38. Curry MP. Direct acting antivirals for decompensated cirrhosis. Efficacy and safety are now established. J Hepatol. 2016;64(6): 1206-1207.
39. Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59(3):1144-1165.
40. Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016;36(suppl 1):47-57.
41. Kyvernitakis A, Mahale P, Torres HA. Safety and tolerability of different antiviral regimens for chronic hepatitis c virus infection in cancer patients [abstract]. Hepatol Int. 2015;9(suppl): S272. Abstract 1235.
42. Mahale P, Kyvernitakis A, Kantarjian H, et al. Concomitant use of chemotherapy and antivirals in hepatitis C virus infected cancer patients [abstract]. Proceedings from the 66th Annual Meeting of the American Association for the Study of Liver Diseases. November 13-17, 2015; San Francisco, CA. Abstract 1160.
43. Shuhart MC, Myerson D, Childs BH, et al. Marrow transplantation from hepatitis C virus seropositive donors: transmission rate and clinical course. Blood. 1994;84(9):3229-3235.
44. Hsiao HH, Liu YC, Wang HC, et al. Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant. Transpl Infect Dis. 2014;16(6):1003-1006.
45. Vance EA, Soiffer RJ, McDonald GB, Myerson D, Fingeroth J, Ritz J. Prevention of transmission of hepatitis C virus in bone marrow transplantation by treating the donor with alpha-interferon. Transplantation. 1996;62(9):1358-1360.
46. Beckerich F, Hézode C, Robin C, et al. New nucleotide polymerase inhibitors to rapidly permit hematopoietic stem cell donation from a positive HCV-RNA donor. Blood. 2014;124(16): 2613-2614.
47. Strasser SI, Myerson D, Spurgeon CL, et al. Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up. Hepatology. 1999;29(6):1893-1899.
48. Pasquini M, Zhu X. Current use and outcome of hematopoietic stem cell transplantation CIBMTR summary slides. 2014.
49. Stirnimann G, Reichen J. Drug prescription in liver disease. In: Hawkey JC, Bosh J, Ritcher JE, Garcia-Tsao G, Chan, FKL, eds. Textbook of Clinical Gastroenterology and Hepatology. 2nd ed. Oxford, United Kingdom: Blackwell Publishing Ltd.; 2012:1077-1081.
50. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther. 2013;37(12): 1132-1156.
51. Field KM, Dow C, Michael M. Part I: Liver function in oncology: biochemistry and beyond. Lancet Oncol. 2008;9(11):1092-1101.
52. Field KM, Michael M. Part II: Liver function in oncology: towards safer chemotherapy use. Lancet Oncol. 2008;9(12):1181-1190.
53. Bodge MN, Culos KA, Haider SN, Thompson MS, Savani BN. Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic hepatic impairment: analysis of the literature and recommendations. Biol Blood Marrow Transplant. 2014;20(5): 622-629.
54. McDonald GB. Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology. 2010;51(4):1450-1460.
55. McDonald GB, Slattery JT, Bouvier ME, et al. Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood. 2003;101(5):2043-2048.
56. de Jonge ME, Huitema AD, Tukker AC, van Dam SM, Rodenhuis S, Beijnen JH. Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy. Clin Cancer Res. 2005;11(1):273-283.
57. de Jonge ME, van den Bongard HJ, Huitema AD, et al. Bayesian pharmacokinetically guided dosing of paclitaxel in patients with non-small cell lung cancer. Clin Cancer Res. 2004;10(7):2237-2244.
58. Furman WL, Baker SD, Pratt CB, Rivera GK, Evans WE, Stewart CF. Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia. J Clin Oncol. 1996;14(5):1504-1511.
59. Radich JP, Gooley T, Bensinger W, et al. HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen. Blood. 2003;102(1):31-35.
60. Slattery JT, Sanders JE, Buckner CD, et al. Graftrejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant. 1995;16(1):31-42.
61. McCune JS, Batchelder A, Guthrie KA, et al. Personalized dosing of cyclophosphamide in the total body irradiation-cyclophosphamide conditioning regimen: a phase II trial in patients with hematologic malignancy. Clin Pharmacol Ther. 2009;85(6):615-622.
62. Nath CE, Trotman J, Tiley C, et al. High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation. Br J Clin Pharmacol. 2016;82(1):149-159.
63. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research. Guidance for industry. Pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072123.pdf. 2003. Accessed July 28, 2016.
64. Floyd J, Kerr TA, eds. Chemotherapy hepatotoxicity and dose modification in patients with liver disease. In: Drews RE, Lindor KD, eds. Waltham, MA: UpToDate. Available at: http://www.uptodate.com. 2016. Accessed July 28, 2016.
65. McDonald GB, McCune JS, Batchelder A, et al. Metabolism-based cyclophosphamide dosing for hematopoietic cell transplant. Clin Pharmacol Ther. 2005;78(3):298-308.
66. Rezvani AR, McCune JS, Storer BE, et al. Cyclophosphamide followed by intravenous targeted busulfan for allogeneic hematopoietic cell transplantation: pharmacokinetics and clinical outcomes. Biol Blood Marrow Transplant. 2013; 19(7):1033-1039.
67. Hogan WJ, Maris M, Storer B, et al. Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients. Blood. 2004;103(1):78-84.
68. McDonald GB, Frieze D. A problem-oriented approach to liver disease in oncology patients. Gut. 2008;57(7):987-1003.
69. Stine JG, Lewis JH. Hepatotoxicity of antibiotics: a review and update for the clinician. Clin Liver Dis. 2013;17(4):609-642, ix.
70. Kaplowitz N, DeLeve LD. Drug-Induced Liver Disease. 3rd ed. London, United Kingdom: Elsevier Inc.; 2013.
71. Li H, Mager DE, Sandmaier BM, Maloney DG, Bemer MJ, McCune JS. Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil. J Clin Pharmacol. 2013;53(4):393-402.
72. DeLeve LD. Cancer chemotherapy. In: Kaplowitz N, DeLeve LD, eds. Drug-Induced Liver Disease. 3rd ed. London, United Kingdom: Elsevier Inc.; 2013:541-567.
73. de Pree C, Giostra E, Galetto A, Perrin L, Zulian GB. Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma. Ann Oncol. 1994;5(9):861-862.
74. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA. 2000;283(1):74-80.
75. Davies SE, Portmann BC, O'Grady JG, et al. Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Hepatology. 1991;13(1):150-157.
76. Dixon LR, Crawford JM. Early histologic changes in fibrosing cholestatic hepatitis C. Liver Transpl. 2007;13(2):219-226.
77. Ceballos-Viro J, López-Picazo JM, Pérez-Gracia JL, Sola JJ, Aisa G, Gil-Bazo I. Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer. World J Gastroenterol. 2009;15(18):2290-2292.
78. Cooksley WG, McIvor CA. Fibrosing cholestatic hepatitis and HBV after bone marrow transplantation. Biomed Pharmacother. 1995; 49(3):117-124.
79. Delladetsima JK, Boletis JN, Makris F, Psichogiou M, Kostakis A, Hatzakis A. Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis C virus infection. Liver Transpl Surg. 1999;5(4):294-300.
80. Lau JY, Bain VG, Davies SE, et al. High-level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis. Gastroenterology. 1992; 102(3):956-962.
81. Kornberg A, Küpper B, Tannapfel A, Hommann M, Scheele J. Impact of mycophenolate mofetil versus azathioprine on early recurrence of hepatitis C after liver transplantation. Int Immunopharmacol. 2005;5(1):107-115.
82. Giard JM, Terrault NA. Severe cholestatic hepatitis C in transplant recipients: no longer a threat to graft survival. Clin Gastroenterol Hepatol. 2015;13(11):2002-2004.
83. Leroy V, Dumortier J, Coilly A, et al. Efficacy of sofosbuvir and daclatasvir in patients with fibrosing cholestatic hepatitis C after liver transplantation. Clin Gastroenterol Hepatol. 2015; 13(11):1993-2001.
84. Charlton M, Everson GT, Flamm SL, et al; SOLAR-1 Investigators. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649-659.
85. Lau GK, He ML, Fong DY, et al. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation. Hepatology. 2002;36(3):702-709.
86. Bosch M, Khan FM, Storek J. Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol. 2012;19(4): 324-335.
87. Clave E, Busson M, Douay C, et al. Acute graftversus-host disease transiently impairs thymic output in young patients after allogeneic hematopoietic stem cell transplantation. Blood. 2009;113(25):6477-6484.
88. Dick TB, Lindberg LS, Ramirez DD, Charlton MR. A clinician's guide to drug-drug interactions with direct-acting antiviral agents for the treatment of hepatitis C viral infection. Hepatology. 2016;63(2): 634-643.
89. Sebhatu P, Martin MT. Genotype 1 hepatitis C virus and the pharmacist's role in treatment. Am J Health Syst Pharm. 2016;73(11):764-774.
90. Höner Zu Siederdissen C, Maasoumy B, Marra F, et al. Drug-drug interactions with novel all oral interferon-free antiviral agents in a large realworld cohort. Clin Infect Dis. 2016;62(5):561-567.
91. MacBrayne CE, Kiser JJ. Pharmacologic considerations in the treatment of hepatitis C virus in persons with HIV. Clin Infect Dis. 2016;63(suppl 1): S12-S23.
92. Torres HA, Adachi JA, Roach LR, et al. Hepatitis C clinic operated by infectious disease specialists at a comprehensive cancer center: help is on the way. Clin Infect Dis. 2012;54(5):740-742.
93. Daklinza (daclatasvir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2016.
94. Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016.
95. Harvoni (ledipasvir and sofosbuvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; 2016.
96. Olysio (simeprevir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2016.
97. Sovaldi (sofosbuvir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2015.
98. Viekira pak (ombitasvir p, and ritonavir tablets; dasabuvir tablets) [prescribing information]. North Chicago, IL: AbbVie Inc.; 2016.
99. Zepatier (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc.; 2016.