DOI QR코드

DOI QR Code

Hepatitis C Viral Infection in Children: Updated Review

  • El-Guindi, Mohamed A. (Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufiya University)
  • Received : 2016.02.15
  • Accepted : 2016.02.29
  • Published : 2016.06.30

Abstract

Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

References

  1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989;244:359-62. https://doi.org/10.1126/science.2523562
  2. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61: 77-87. https://doi.org/10.1002/hep.27259
  3. Jhaveri R. Diagnosis and management of hepatitis C virus- infected children. Pediatr Infect Dis J 2011;30: 983-5. https://doi.org/10.1097/INF.0b013e318236ac37
  4. El-Raziky MS, El-Hawary M, Esmat G, Abouzied AM, El-Koofy N, Mohsen N, et al. Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children. World J Gastroenterol 2007;13:1828-32. https://doi.org/10.3748/wjg.v13.i12.1828
  5. Bare P. Hepatitis C virus and peripheral blood mononuclear cell reservoirs Patricia Bare. World J Hepatol 2009;1:67-71. https://doi.org/10.4254/wjh.v1.i1.67
  6. Kato N. Genome of human hepatitis C virus (HCV): gene organization, sequence diversity, and variation. Microb Comp Genomics 2000;5:129-51. https://doi.org/10.1089/omi.1.2000.5.129
  7. Kim CW, Chang KM. Hepatitis C virus: virology and life cycle. Clin Mol Hepatol 2013;19:17-25. https://doi.org/10.3350/cmh.2013.19.1.17
  8. Alvisi G, Madan V, Bartenschlager R. Hepatitis C virus and host cell lipids: an intimate connection. RNA Biol 2011;8:258-69. https://doi.org/10.4161/rna.8.2.15011
  9. Kaplan DE, Sugimoto K, Newton K, Valiga ME, Ikeda F, Aytaman A, et al. Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology 2007; 132:654-66. https://doi.org/10.1053/j.gastro.2006.11.044
  10. Logvinoff C, Major ME, Oldach D, Heyward S, Talal A, Balfe P, et al. Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc Natl Acad Sci U S A 2004;101:10149-54. https://doi.org/10.1073/pnas.0403519101
  11. von Hahn T, Yoon JC, Alter H, Rice CM, Rehermann B, Balfe P, et al. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 2007;132: 667-78. https://doi.org/10.1053/j.gastro.2006.12.008
  12. Isken O, Langerwisch U, Jirasko V, Rehders D, Redecke L, Ramanathan H, et al. A conserved NS3 surface patch orchestrates NS2 protease stimulation, NS5A hyperphosphorylation and HCV genome replication. PLoS Pathog 2015;11:e1004736. https://doi.org/10.1371/journal.ppat.1004736
  13. Liang TJ. Current progress in development of hepatitis C virus vaccines. Nat Med 2013;19:869-78. https://doi.org/10.1038/nm.3183
  14. Zeisel MB, Barth H, Schuster C, Baumert TF. Hepatitis C virus entry: molecular mechanisms and targets for antiviral therapy. Front Biosci (Landmark Ed) 2009; 14:3274-85.
  15. Bartenschlager R, Penin F, Lohmann V, Andre P. Assembly of infectious hepatitis C virus particles. Trends Microbiol 2011;19:95-103. https://doi.org/10.1016/j.tim.2010.11.005
  16. Bartenschlager R, Lohmann V. Replication of hepatitis C virus. J Gen Virol 2000;81:1631-48. https://doi.org/10.1099/0022-1317-81-7-1631
  17. Kohaar I, Ploss A, Korol E, Mu K, Schoggins JW, O'Brien TR, et al. Splicing diversity of the human OCLN gene and its biological significance for hepatitis C virus entry. J Virol 2010;84:6987-94. https://doi.org/10.1128/JVI.00196-10
  18. Syed GH, Amako Y, Siddiqui A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab 2010;21:33-40. https://doi.org/10.1016/j.tem.2009.07.005
  19. Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 2013;19:837-49. https://doi.org/10.1038/nm.3248
  20. Horner SM, Gale M Jr. Regulation of hepatic innate immunity by hepatitis C virus. Nat Med 2013;19:879-88. https://doi.org/10.1038/nm.3253
  21. Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol 2007;5:453-63. https://doi.org/10.1038/nrmicro1645
  22. Pawlowska M, Domagalski K, Pniewska A, Smok B, Halota W, Tretyn A. What's new in hepatitis C virus infections in children? World J Gastroenterol 2015;21: 10783-9. https://doi.org/10.3748/wjg.v21.i38.10783
  23. World Health Organization. WHO Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection. Fact Sheet 2015, $N^{\circ}$ 164. Updated July 2015.
  24. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000;355:887-91. https://doi.org/10.1016/S0140-6736(99)06527-7
  25. Yeung CY, Lee HC, Chan WT, Jiang CB, Chang SW, Chuang CK. Vertical transmission of hepatitis C virus: Current knowledge and perspectives. World J Hepatol 2014;6:643-51. https://doi.org/10.4254/wjh.v6.i9.643
  26. Bortolotti F, Iorio R, Resti M, Camma C, Marcellini M, Giacchino R, et al; Italian Observatory for HCV Infection and Hepatitis C in Children. Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period. J Hepatol 2007;46:783-90. https://doi.org/10.1016/j.jhep.2006.12.014
  27. Roberts EA, Yeung L. Maternal-infant transmission of hepatitis C virus infection. Hepatology 2002;36(5 Suppl 1):S106-13. https://doi.org/10.1002/hep.1840360714
  28. Checa Cabot CA, Stoszek SK, Quarleri J, Losso MH, Ivalo S, Peixoto MF, et al; NICHD International Site Development Initiative Perinatal/Longitudinal Study in Latin American Countries Study Group. Mother-tochild transmission of hepatitis C virus (HCV) among HIV/HCV-coinfected women. J Pediatric Infect Dis Soc 2013;2:126-35. https://doi.org/10.1093/jpids/pis091
  29. Shebl FM, El-Kamary SS, Saleh DA, Abdel-Hamid M, Mikhail N, Allam A, et al. Prospective cohort study of mother-to-infant infection and clearance of hepatitis C in rural Egyptian villages. J Med Virol 2009;81: 1024-31. https://doi.org/10.1002/jmv.21480
  30. Jara P, Resti M, Hierro L, Giacchino R, Barbera C, Zancan L, et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003;36:275-80. https://doi.org/10.1086/345908
  31. Jara P, Hierro L. Treatment of hepatitis C in children. Expert Rev Gastroenterol Hepatol 2010;4:51-61. https://doi.org/10.1586/egh.09.76
  32. Bortolotti F, Resti M, Marcellini M, Giacchino R, Verucchi G, Nebbia G, et al. Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome. Gut 2005;54:852-7. https://doi.org/10.1136/gut.2004.053744
  33. European Paediatric Hepatitis C Virus Network. Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 2005;41:45-51. https://doi.org/10.1086/430601
  34. Pembrey L, Newell ML, Tovo PA; EPHN Collaborators. The management of HCV infected pregnant women and their children European paediatric HCV network. J Hepatol 2005;43:515-25. https://doi.org/10.1016/j.jhep.2005.06.002
  35. Akhter A, Said A. Cutaneous manifestations of viral hepatitis. Curr Infect Dis Rep 2015;17:452.
  36. Alkhouri N, Zein NN. Hepatitis C in children and adolescents: the good, the bad, and the ugly. Curr Hepat Reports 2008;7:145-51. https://doi.org/10.1007/s11901-008-0029-8
  37. Bortolotti F, Verucchi G, Camma C, Cabibbo G, Zancan L, Indolfi G, et al; Italian Observatory for HCV Infection and Hepatitis C in Children. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 2008;134: 1900-7. https://doi.org/10.1053/j.gastro.2008.02.082
  38. Bortolotti F, Muratori L, Jara P, Hierro L, Verucchi G, Giacchino R, et al. Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children. J Pediatr 2003;142:185-90. https://doi.org/10.1067/mpd.2003.45
  39. Rumbo C, Fawaz RL, Emre SH, Suchy FJ, Kerkar N, Morotti RA, et al. Hepatitis C in children: a quaternary referral center perspective. J Pediatr Gastroenterol Nutr 2006;43:209-16. https://doi.org/10.1097/01.mpg.0000228117.52229.32
  40. Gonzalez-Peralta RP, Langham MR Jr, Andres JM, Mohan P, Colombani PM, Alford MK, et al. Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2009;48:630-5. https://doi.org/10.1097/MPG.0b013e318170af04
  41. Barshes NR, Udell IW, Lee TC, O'Mahony CA, Karpen SJ, Carter BA, et al. The natural history of hepatitis C virus in pediatric liver transplant recipients. Liver Transpl 2006;12:1119-23. https://doi.org/10.1002/lt.20793
  42. Chevaliez S, Pawlotsky JM. Diagnosis and management of chronic viral hepatitis: antigens, antibodies and viral genomes. Best Pract Res Clin Gastroenterol 2008;22:1031-48. https://doi.org/10.1016/j.bpg.2008.11.004
  43. Kamili S, Drobeniuc J, Araujo AC, Hayden TM. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis 2012;55 Suppl 1:S43-8. https://doi.org/10.1093/cid/cis368
  44. Park MS, Kim BK, Cheong JY, Kim DJ, Park JY, Kim do Y, et al. Discordance between liver biopsy and FibroTest in assessing liver fibrosis in chronic hepatitis B. PLoS One 2013;8:e55759. https://doi.org/10.1371/journal.pone.0055759
  45. Russo P, Ruchelli ED, Piccoli DA. Pathology of pediatric gastrointestinal and liver disease. 2nd ed. Berlin: Springer, 2014:371-93.
  46. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431-5. https://doi.org/10.1002/hep.1840010511
  47. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696-9. https://doi.org/10.1016/0168-8278(95)80226-6
  48. Theise ND. Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. Mod Pathol 2007;20 Suppl 1:S3-14. https://doi.org/10.1038/modpathol.3800693
  49. Guido M, Bortolotti F, Leandro G, Jara P, Hierro L, Larrauri J, et al. Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time? Am J Gastroenterol 2003;98:660-3. https://doi.org/10.1111/j.1572-0241.2003.07293.x
  50. Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-Peralta RP, Haber B, et al. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology 2008;47:836-43. https://doi.org/10.1002/hep.22094
  51. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008;371:838-51. https://doi.org/10.1016/S0140-6736(08)60383-9
  52. European Association for Study of Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 2015;63:199-236. https://doi.org/10.1016/j.jhep.2015.03.025
  53. El Naghi S, Abdel-Ghaffar TY, El-Karaksy H, Abdel-Aty EF, El-Raziky MS, Allam AA, et al. Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children. World J Gastroenterol 2014;20:4681-91. https://doi.org/10.3748/wjg.v20.i16.4681
  54. Department of Veterans Affairs Hepatitis C Resource Center, Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J Gastroenterol 2006;101:2360-78. https://doi.org/10.1111/j.1572-0241.2006.00754.x
  55. Kamal SM. Hepatitis C genotype 4 therapy: increasing options and improving outcomes. Liver Int 2009;29 Suppl 1:39-48. https://doi.org/10.1111/j.1478-3231.2008.01930.x
  56. Varghese R, Al-Khaldi J, Asker H, Fadili AA, Al Ali J, Hassan FA. Treatment of chronic hepatitis C genotype 4 with peginterferon alpha-2a plus ribavirin. Hepatogastroenterology 2009;56:218-22.
  57. Lee CK, Jonas MM. Treating HCV infection in children. Clin Liver Dis 2015;5:14-6. https://doi.org/10.1002/cld.439
  58. Hofmann WP, Sarrazin C, Zeuzem S. Current standards in the treatment of chronic hepatitis C. Dtsch Arztebl Int 2012;109:352-8.
  59. Navaneethan U, Kemmer N, Neff GW. Predicting the probable outcome of treatment in HCV patients. Therap Adv Gastroenterol 2009;2:287-302. https://doi.org/10.1177/1756283X09339079
  60. Noureddin M, Ghany MG. Pharmacokinetics and pharmacodynamics of peginterferon and ribavirin: implications for clinical efficacy in the treatment of chronic hepatitis C. Gastroenterol Clin North Am 2010;39: 649-58. https://doi.org/10.1016/j.gtc.2010.08.008
  61. FDA News Release. FDA approves rapid test for antibodies to hepatitis C virus. Silver Spring: U.S. Food and Drug Administration, 2010.
  62. Yeung LT, Roberts EA. Current issues in the management of paediatric viral hepatitis. Liver Int 2010; 30:5-18. https://doi.org/10.1111/j.1478-3231.2009.02145.x
  63. Scherzer TM, Reddy KR, Wrba F, Hofer H, Staufer K, Steindl-Munda P, et al. Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C. J Viral Hepat 2008;15:659-65. https://doi.org/10.1111/j.1365-2893.2008.01006.x
  64. Iorio R, Giannattasio A, Sepe A, Terracciano LM, Vecchione R, Vegnente A. Chronic hepatitis C in childhood: an 18-year experience. Clin Infect Dis 2005;41: 1431-7. https://doi.org/10.1086/497141
  65. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401. https://doi.org/10.1038/nature08309
  66. Villar LM, Cruz HM, Barbosa JR, Bezerra CS, Portilho MM, Scalioni Lde P. Update on hepatitis B and C virus diagnosis. World J Virol 2015;4:323-42. https://doi.org/10.5501/wjv.v4.i4.323
  67. Jara P, Hierro L, de la Vega A, Diaz C, Camarena C, Frauca E, et al. Efficacy and safety of peginterferon- alpha2b and ribavirin combination therapy in children with chronic hepatitis C infection. Pediatr Infect Dis J 2008;27:142-8.
  68. Wirth S, Pieper-Boustani H, Lang T, Ballauff A, Kullmer U, Gerner P, et al. Peginterferon alfa-2b plus ribavirin treatment in children and adolescents with chronic hepatitis C. Hepatology 2005;41:1013-8. https://doi.org/10.1002/hep.20661
  69. Bortolotti F, Iorio R, Nebbia G, Marcellini M, Giacchino R, Zancan L, et al. Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in nonresponders. Dig Liver Dis 2005;37:336-41. https://doi.org/10.1016/j.dld.2004.12.010
  70. Jonas MM, Balistreri W, Gonzalez-Peralta RP, Haber B, Lobritto S, Mohan P, et al. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology 2012;56:523-31. https://doi.org/10.1002/hep.25690
  71. Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz MR, Roberts EA, et al; North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. NASPGHAN practice guidelines: diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr 2012;54:838-55. https://doi.org/10.1097/MPG.0b013e318258328d
  72. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, et al; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364:2417-28. https://doi.org/10.1056/NEJMoa1013086
  73. Charlton M, Gane E, Manns MP, Brown RS Jr, Curry MP, Kwo PY, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology 2015;148:108-17. https://doi.org/10.1053/j.gastro.2014.10.001
  74. Forns X, Prieto M, Charlton M, McHutchison JG, Symonds WT, Denning J, et al. O62 sofosbuvir compassionate use program for patients with severe recurrent hepatitis c including fibrosing cholestatic hepatitis following liver transplantation. J Hepatol 2014;60 (Suppl):S26.
  75. Kwo P, Gitlin N, Nahass R, Bernstein D, Etzkorn K, Rojter S, et al. Simeprevir plus sofosbuvir (12 and 8 weeks) in HCV genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology 2016. doi: 10.1002/hep.28467. [Epub ahead of print]
  76. Reddy KR, Everson GT, Flamm SL, Denning JM, Arterburn S, Brandt-Sarif T, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post-transplant recurrence: preliminary results of a prospective, multicenter study. Hepatology 2014;60: 200A-1A. https://doi.org/10.1002/hep.27449
  77. Mantry P, Kwo P, Coakley E, Te H, Vargas H, Brown RS, et al. High sustained virologic response rates in liver transplant recipients with recurrent HCV genotype 1 infection receiving ABT-450/R/ombitasvir+dasabuvir plus ribavirin. Paper presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014 Nov 7-11; Boston, USA. p. 298A.
  78. Brown RS, Reddy KR, O'Leary JG, Kuo A, Morelli G, Stravitz RT, et al. Safety and efficacy of new DAA-based therapy for hepatitis C post-transplant: interval results from the HCV-TARGET longitudinal, observational study. Paper presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014 Nov 7-11; Boston, USA. p. 1269A.
  79. Leroy V, Dumortier J, Coilly A, Sebagh M, Fougerou- Leurent C, Radenne S, et al. High rates of virological response and major clinical improvement during sofosbuvir and daclatasvir-based regimens for the treatment of fibrosing cholestatic HCV-recurrence after liver transplantation: the ANRS CO23 CUPILT study. Transpl Int 2015;28:14.
  80. Lawitz E, Poordad F, Hyland RH, Liu L, Dvory HS, Pang PS, et al. High rates of SVR in treatment-experienced patients with genotype 1 HCV infection and cirrhosis after treatment with ledipasvir/sofosbuvir and vedroprevir with or without ribavirin for 8 weeks. Paper presented at: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; Boston, USA. p. 337A.
  81. Kwo P, Bennett M, Wang S, Vargas HE, Wyles D, Overcash JS, et al. SURVEYOR-II: high SVR4 rates achieved with the next generation NS3/4A protease inhibitor ABT-493 and NS5A inhibitor ABT-530 in non-cirrhotic treatment-naive and treatment-experienced patients with HCV genotype 3 infection. Paper presented at: Frontiers in Drug Development for Viral Hepatitis; 2015 Dec 6-10; Wailea, USA. p. 337A-338A.
  82. Alessandra MA, Stuart K. Roberts SK, Pianko S, Thompson AJ, Cooper C, et al. Sofosbuvir/GS-5816 fixed dose combination for 12 weeks compared to sofosbuvir with ribavirin for 24 weeks in genotype 3 hcv infected patients: the randomized controlled phase 3 ASTRAL-3 study. Hetatology 2015;62(Suppl 1):338A.
  83. Wyles D, Sulkowski M, Wang S, Bennett M, Vargas HE, Overcash JS, et al. SURVEYOR-II: high SVR4 rates achieved with the next generation NS3/4A protease inhibitor ABT-493 and NS5A inhibitor ABT-530 in non-cirrhotic treatment-naive and treatment-experienced patients with HCV genotype 2 infection. Paper presented at: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; Boston, USA. p. 339A.
  84. Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros P, Robertson M, et al. High efficacy of elbasvir and grazoprevir with or without ribavirin in 103 treatment- naive and experienced patients with HCV genotype 4 infection: a pooled analysis. Paper presented at: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; Boston, USA. p. 339A.
  85. Herzer K, Welzel TM, Ferenci P, Petersen J, Gschwantler M, Cornberg M, et al. Daclatasvir in combination with sofosbuvir with or without ribavirin is safe and efficacious in liver transplant recipients with HCV recurrence: interim results of a European multicenter compassionate use program. Paper presented at: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; Boston, USA. p. 339A.
  86. Welzel TM, Petersen J, Ferenci P, Gschwantler M, Herzer K, Cornberg M, et al. Safety and efficacy of daclatasvir plus sofosbuvir with or without ribavirin for the treatment of chronic HCV genotype 3 infection: interim results of a multicenter European compassionate use program. Paper presented at: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015 Nov 13-17; Boston, USA. p. 225A.
  87. Lawitz E, Poordad F, Gutierrez JA, Kakuda T, Picchio G, Beets G, et al. SVR12 results from the Phase II, open-label IMPACT. Study of simeprevir (SMV) in combination with daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive and -experienced patients with chronic HCV genotype 1/4 infection and decompensated liver disease. Hepatology 2015;62(Suppl 1): 227A.
  88. Poordad F, Felizarta F, Asatryan A, Hassanein TI, Aguilar HI, Lalezari JP, et al. 98%-100% SVR4 in HCV genotype 1 non-cirrhotic treatment-naive or pegylated interferon/ribavirin null responders with the combination of the next generation NS3/4A protease inhibitor ABT-493 and NS5A inhibitor ABT-530 (SURVEYOR-1). Hepatology 2015;62(Suppl 1):228A.
  89. Gane EJ, Hyland RH, Yang Y, Stamm LM, Brainard DM, McHutchison JG, et al. Sofosbuvir/GS-5816+GS- 9857 for 6 or 8 weeks in genotype 1 or 3 HCV-infected patients. Hepatology 2015;62(Suppl 1):227A.
  90. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology 2015;62:932-54. https://doi.org/10.1002/hep.27950