Management of HCV in Cirrhosis—a Rapidly Evolving Landscape

Current Gastroenterology Reports

Volumn 17, Issue 5, 2015, Pages 1-11

  Sharma, Suraj A ^a   Feld, Jordan J ^a  

^a UNIVERSITY HEALTH NETWORK   (Canada)

Author keywords

Cirrhosis; Decompensation; Direct acting antivirals (DAA); Epidemiology; Hepatitis C; Peginterferon; Sustained virologic response

Indexed keywords

ALBUMIN; ANTIVIRUS AGENT; ASUNAPREVIR; BILIRUBIN; BOCEPREVIR; DACLATASVIR; DASABUVIR; GRAZOPREVIR; GS 5816; LEDIPASVIR; LEDIPASVIR PLUS SOFOSBUVIR; LIVER ENZYME; OMBITASVIR; PARITAPREVIR; PEGINTERFERON; RIBAVIRIN; RITONAVIR; SIMEPREVIR; SOFOSBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; ALPHA INTERFERON; N-(3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL)-3-(2-((((1,1-DIMETHYLETHYL)AMINO)CARBONYL)AMINO)-3,3-DIMETHYL-1-OXOBUTYL)-6,6-DIMETHYL-3-AZABICYCLO(3.1.0)HEXAN-2-CARBOXAMIDE; OLIGOPEPTIDE; PROLINE;

ALBUMIN BLOOD LEVEL; ASCITES; BILIRUBIN BLOOD LEVEL; BRAIN DISEASE; DECOMPENSATED LIVER CIRRHOSIS; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; HEPATITIS C; HEPATITIS C VIRUS GENOTYPE 2; HEPATITIS C VIRUS GENOTYPE 3; HEPATITIS C VIRUS GENOTYPE 4; HEPATITIS C VIRUS GENOTYPE 5; HEPATITIS C VIRUS GENOTYPE 6; HUMAN; INFECTION; LIVER CIRRHOSIS; REVIEW; SEPSIS; SUSTAINED VIROLOGICAL RESPONSE; THROMBOCYTE COUNT; TREATMENT CONTRAINDICATION; TREATMENT RESPONSE; ANALOGS AND DERIVATIVES; COMPLICATION; GENETICS; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; VIROLOGY;

ANTIVIRAL AGENTS; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; INTERFERON-ALPHA; LIVER CIRRHOSIS; OLIGOPEPTIDES; PROLINE;

EID: 84928407715     PISSN: 15228037     EISSN: 1534312X     Source Type: Journal    
DOI: 10.1007/s11894-015-0443-3     Document Type: Review

References (82)

1. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age‐specific antibody to HCV seroprevalence. Hepatology. 2013;57:1333–42.
2. Global Burden of Hepatitis C Working Group. Global burden of disease (GBD) for hepatitis C. J Clin Pharmacol. 2004;44:20–9.
3. Lavanchy D. The global burden of hepatitis C. Liver Int. 2009;29 Suppl 1:74–81.
4. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–72.
5. Thein H-H, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology. 2008;48:418–31.
6. Kanwal F, Kramer JR, Ilyas J, Duan Z, El-Serag HB. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. veterans with HCV. Hepatology. 2014;60:98–105.
7. Shahid M, Idrees M, Nasir B, Raja AJ, Raza SM, Amin I, et al. Correlation of biochemical markers and HCV RNA titers with fibrosis stages and grades in chronic HCV-3a patients. Eur J Gastroenterol Hepatol. 2014;26:788–94.
8. Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013;158:658–66.
9. Feld JJ, Liang TJ. Hepatitis C—identifying patients with progressive liver injury. Hepatology. 2006;43:S194–206.
10. Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34:809–16.
11. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–32.
12. Hui C-K, Belaye T, Montegrande K, Wright TL. A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase. J Hepatol. 2003;38:511–7.
13. Chu C-J, Lee S-D. Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment. J Gastroenterol Hepatol. 2008;23:512–20.
14. Gonzalez F, Van den Eynde E, Perez-Hoyos S, Navarro J, Curran A, Burgos J, et al. Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV-coinfected patients. HIV Med. 2014. doi:10.1111/hiv.12197.
15. Probst A, Dang T, Bochud M, Egger M, Negro F, Bochud P-Y. Role of hepatitis C virus genotype 3 in liver fibrosis progression—a systematic review and meta-analysis. J Viral Hepat. 2011;18:745–59.
16. Patin E, Kutalik Z, Guergnon J, Bibert S, Nalpas B, Jouanguy E, et al. Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection. Gastroenterology. 2012;143:1244–52.e1–12.
17. Zarski J-P, Mc Hutchison J, Bronowicki J-P, Sturm N, Garcia-Kennedy R, Hodaj E, et al. Rate of natural disease progression in patients with chronic hepatitis C. J Hepatol. 2003;38:307–14.
18. Wedemeyer H, Dore GJ, Ward JW. Estimates on HCV disease burden worldwide—filling the gaps. J Viral Hepat. 2015;22 Suppl 1:1–5. This paper summarizes the global epidemiology of HCV and the burden of disease in 2015.
19. Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today’s treatment paradigm. J Viral Hepat. 2014;21 Suppl 1:34–59.
20. Rein DB, Wittenborn JS, Weinbaum CM, Sabin M, Smith BD, Lesesne SB. Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States. Dig Liver Dis. 2011;43:66–72.
21. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002;122:1303–13.
22. Veldt BJ, Saracco G, Boyer N, Cammà C, Bellobuono A, Hopf U, et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut. 2004;53:1504–8.
23. Aleman S, Rahbin N, Weiland O, Davidsdottir L, Hedenstierna M, Rose N, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis Oxford Univ Press. 2013;57:230–6.
24. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour J-F, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584–93.
25. Schvarcz R, Ando Y, Sönnerborg A, Weiland O. Combination treatment with interferon alfa-2b and ribavirin for chronic hepatitis C in patients who have failed to achieve sustained response to interferon alone: Swedish experience. J Hepatol. 1995;23 Suppl 2:17–21.
26. Kakumu S, Yoshioka K, Wakita T, Ishikawa T, Takayanagi M, Higashi Y. A pilot study of ribavirin and interferon beta for the treatment of chronic hepatitis C. Gastroenterology. 1993;105:507–12.
27. McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580–93.
28. Heathcote EJ, Shiffman ML, Cooksley WG, Dusheiko GM, Lee SS, Balart L, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med. 2000;343:1673–80.
29. Kim KH, Jang BK, Chung WJ, Hwang JS, Kweon YO, Tak WY, et al. Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C virus-related liver cirrhosis. Korean J Hepatol. 2011;17:220–5.
30. Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, et al. Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis. Antivir Ther (Lond). 2008;13:663–73.
31. Yu M-L, Dai C-Y, Huang J-F, Hou N-J, Lee L-P, Hsieh M-Y, et al. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007;56:553–9.
32. Everson GT, Trotter J, Forman L, Kugelmas M, Halprin A, Fey B, et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology. 2005;42:255–62.
33. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–16.
34. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014;384:1756–65.
35. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–17.
36. Hézode C, Fontaine H, Dorival C, Larrey D, Zoulim F, Canva V, et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) - NCT01514890. J Hepatol. 2013;59:434–41. Real world data on the safety of boceprevir and telaprevir, showing high rates of adverse events, especially in cirrhotic patients.
37. Hézode C, Fontaine H, Dorival C, Zoulim F, Larrey D, Canva V, et al. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. Gastroenterology. 2014;147:132–4.
38. Flamm SL, Everson GT, M C. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with decompensated cirrhosis: preliminary results of a prospective, multicenter study. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 239. This important abstract describes the efficacy and safety of sofosbuvir/ledipasvir in decompensated cirrhosis.
39. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–24.
40. Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59:2083–91.
41. Jacobson IM, Dore GJ, Foster GR, Fried MW, Radu M, Rafalsky VV, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014;384:403–13.
42. Hézode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, Shafran SD, et al. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study. Gut. BMJ Publishing Group Ltd and British Society of Gastroenterology. 2014; gutjnl–2014–307498.
43. Reichard O, Andersson J, Schvarcz R, Weiland O. Ribavirin treatment for chronic hepatitis C. Lancet. 1991;337:1058–61.
44. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485–92.
45. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–82.
46. Yee BE, Nguyen NH, Zhang B, Vutien P, Wong CR, Lutchman GA, et al. Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin. Eur J Gastroenterol Hepatol. 2014;26:1189–201.
47. Powis J, Peltekian KM, Lee SS, Sherman M, Bain VG, Cooper C, et al. Exploring differences in response to treatment with peginterferon alpha 2a (40 kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3. J Viral Hepat. 2008;15:52–7.
48. Bota S, Sporea I, Sirli R, Popescu A, Neghină AM, Dănilă M, et al. Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: a systematic review. World J Hepatol. 2013;5:120–6.
49. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417–28.
50. Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206.
51. Welsch C, Jesudian A, Zeuzem S, Jacobson I. New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Gut. 2012;61 Suppl 1:i36–46.
52. Schinazi R, Halfon P, Marcellin P, Asselah T. HCV direct-acting antiviral agents: the best interferon-free combinations. Liver Int. 2014;34 Suppl 1:69–78.
53. Manns M, Marcellin P, Poordad F, de Araujo ESA, Buti M, Horsmans Y, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;384:414–26.
54. Mariño Z, van Bömmel F, Forns X, Berg T. New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C. Gut. 2014;63:207–15.
55. Feld JJ. Interferon-free strategies with a nucleoside/nucleotide analogue. Semin Liver Dis. 2014;34:37–46.
56. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87.
57. Jensen DM, OLeary J, Pockros P, Sherman K. Safety and efficacy of sofosbuvir-containing regimens for hepatitis C: real-world experience in a diverse, longitudinal observational cohort. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 45. This abstract describes the real-world safety and efficacy of sofosbuvir-containing regimens, showing that treatment efficacy and safety is similar to results from large RCTs.
58. Capraru C, Kuczynski M, La D, Kaznowski D. Efficacy and safety of sofosbuvir plus simeprevir in patients with advanced HCV cirrhosis. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 963
59. Svarovskaia ES, Dvory-Sobol H, Parkin N, Hebner C, Gontcharova V, Martin R, et al. Infrequent development of resistance in genotype 1–6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin Infect Dis. 2014;59:1666–74.
60. Gao M. Antiviral activity and resistance of HCV NS5A replication complex inhibitors. Curr Opin Virol. 2013;3:514–20.
61. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889–98.
62. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483–93.
63. FDA 2014 - Label for Harvoni (Sofosbuvir/Ledipasvir) [Internet]. [cited 2015 Jan 26]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf
64. Bourlière M, Bronowicki J-P, de Ledinghen V, Hézode C, Zoulim F, Mathurin P. Ledipasvir/sofosbuvir fixed-dose combination is safe and efficacious in cirrhotic patients who have previously failed protease-inhibitor based triple therapy. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract LB-6
65. Bourlière M, Sulkowski M, Omata M. An integrated safety and efficacy analysis of >500 patients with compensated cirrhosis treated with ledipasvir/sofosbuvir with or without ribavirin. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 82
66. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211–21.
67. Poordad F, Hézode C, Trinh R, Kowdley KV, Zeuzem S, Agarwal K, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370:1973–82.
68. Sulkowski M, Mallolas J, Pol S, Bourliere M, Gerstoft J, Shibolet O, et al. O63 efficacy and safety of the all-oral regimen, Mk-5172/Mk-8742 +/− Rbv for 12 weeks In Gt1 HCV/HIV co-infected patients: The C-WORTHY Study. J Hepatol. 2014;60:S26.
69. Lawitz E. C-SWIFT: Grazoprevir (MK-5172) + elbasvir (MK-8742) + sofosbuvir in treatment-naive patients with hepatitis C virus genotype 1 infection, with and without cirrhosis, for durations of 4, 6, or 8 weeks. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract LB-33.
70. Reddy KR, Everson G, Flamm SL. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 8.
71. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867–77.
72. Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370:1993–2001.
73. Lawitz E, Poordad F, Brainard DM, Hyland RH, An D, Dvory-Sobol H, et al. Sofosbuvir with peginterferon-ribavirin for 12 weeks in previously treated patients with hepatitis C genotype 2 or 3 and cirrhosis. Hepatology. 2014. doi:10.1002/hep.27567.
74. Esteban R, Nyberg L, Lalezari J, Ni L, Doehle B, Kanwar B, et al. Successful retreatment with sofosbuvir-containing regimens for HCV genotype 2 or 3 infected patients who failed prior sofosbuvir plus ribavirin therapy. J Hepatol Elsevier. 2015;60:S4–5.
75. Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase 3 study. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). November 7–11, 2014; Boston, MA; abstract LB-3.
76. Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, et al. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014;57:2033–46.
77. Gane EJ, Hyland RH, An D, Pang PS, Symonds WT, McHutchison JG, et al. Sofosbuvir/ledipasvir fixed dose combination is safe and effective in difficult-to-treat populations including genotype-3 patients, decompensated genotype-1 patients, and genotype-1 patients with prior sofosbuvir treatment experience. J Hepatol. 2014;60:S3–4.
78. Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368:34–44.
79. Pianko S, Flamm SL, Shiffman ML. High Efficacy of Treatment with Sofosbuvir + GS-5816 ± Ribavirin for 12 Weeks in Treatment Experienced Patients with Genotype 1 or 3 HCV Infection. 65th Annual Meeting of the American Association for the Study of Liver Diseases, November 7–11, 2014, Boston, USA; abstract 80.
80. Ruane PJ, Ain D, Stryker R, Meshrekey R, Soliman M, Wolfe PR, et al. Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry. J Hepatol. 2014. doi:10.1016/j.jhep.2014.10.044.
81. Pol S, Reddy RK, Baykal T. Interferon-free regimens of ombitasvir and ABT-450/r with or without ribavirin in patients with HCV genotype 4 infection. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). November 7–11, 2014; Boston, MA; abstract 1928.
82. Kapoor R, Kohli A, Sidharthan S. All oral treatment for genotype 4 chronic hepatitis C infection with sofosbuvir and ledipasvir: interim results from the NIAID SYNERGY trial. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). November 7–11, 2014; Boston, MA; abstract 240.