The "C" of viral hepatitis in children

Seminars in Liver Disease

Volumn 27, Issue 3, 2007, Pages 295-311

  Narkewicz, Michael R ^a   Cabrera, Roniel ^b   González Peralta, Regino P ^b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Children; Hepatitis C virus; Transmission; Treatment

Indexed keywords

A 831; ACH 0137171; ALBUMIN ALPHA INTERFERON; ANTIFIBROTIC AGENT; AVI 4065; BAVITUXIMAB; BETA1A INTERFERON; BIVN 401; BLX 883; CASTANOSPERMINE 6 BUTYRATE; GI 5005; HCV MF 59; IC 41; IMMUNOMODULATING AGENT; INTERFERON; ITMN 191; JBK 122; MERIMEPODIB; MITOQUINONE; NITAZOXANIDE; NOV 205; OGLUFANIDE; PEGINTERFERON; PEGINTERFERON ALPHA2A; PF 03491390; PROTEINASE INHIBITOR; R 1626; R 7128; RIBAMIDINE; RIBAVIRIN; TG 4040; THYMOSIN ALPHA1; UNCLASSIFIED DRUG; UNINDEXED DRUG; VGX 410C; XTL 2125; XTL 6865;

ABDOMINAL PAIN; ANOREXIA; ANTIVIRAL ACTIVITY; BLOOD TRANSFUSION; CHILD; DEPRESSION; FETUS MALFORMATION; FEVER; FLU LIKE SYNDROME; GENOTYPE; GEOGRAPHIC DISTRIBUTION; HEADACHE; HEMOLYTIC ANEMIA; HEPATITIS C; HEPATITIS C VIRUS; HOST; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INCIDENCE; LIFE CYCLE; MYALGIA; NAUSEA; NEUTROPENIA; PERINATAL INFECTION; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SEIZURE; SERUM FACTOR; SIDE EFFECT; SUICIDAL IDEATION; SUICIDE ATTEMPT; THYROID DISEASE; TREATMENT RESPONSE; VERTICAL TRANSMISSION; VIREMIA; VIRUS GENOME; VIRUS TRANSMISSION; WEIGHT REDUCTION;

ANTIVIRAL AGENTS; CHILD; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; INFANT; INFANT, NEWBORN; RISK FACTORS;

EID: 34548169370     PISSN: 02728087     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-985074     Document Type: Review

References (121)

1. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5:558-567
2. World Health Organization. Hepatitis C. Wkly Epidemiol Rec 1997;72:65-72
3. Wong JB, McQuillan GM, McHutchison JG, Poynard T. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000;90:1562-1569
4. Jhaveri R, Grant W, Kauf TL, McHutchison J. The burden of hepatitis C virus infection in children: estimated direct medical costs over a 10-year period. J Pediatr 2006;148:353-358
5. Donahue JG, Munoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med 1992;327:369-373
6. Robertson B, Myers G, Howard C, et al. Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. Arch Virol 1998;143:2493-2503
7. Branch AD, Stump DD, Gutierrez JA, Eng F, Walewski JL. The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. Semin Liver Dis 2005;25:105-117
8. Thomson M, Liang TJ. Molecular biology of hepatitis C virus. In: Liang TJ, Hoofnagle JH, eds. Hepatitis C. San Diego, CA: Academic Press; 2000:1-23
9. Smith RM, Wu GY. Molecular virology of hepatitis B and C. In: Koff RS, Wu GY, eds. Chronic Viral Hepatitis: Diagnosis and Therapeutics. Totowa, NJ: Humana Press; 2002:1-24
10. Tellinghuisen TL, Rice CM. Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol 2002;5:419-427
11. Martell M, Esteban JI, Quer J, et al. Hepatitis C virus circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol 1992;66:3225-3229
12. Moribe T, Hayashi N, Kanasawa Y, et al. Hepatitis C viral complexity detected by single strand conformational polymorphism and response to interferon therapy. Gastroenterology 1995;108:789-795
13. Gonzalez-Peralta RP, Qian K, She JY, et al. Clinical implications of viral quasispecies in chronic hepatitis C. J Med Virol 1996;49:242-247
14. González-Peralta RP, Liu W, Davis GL, et al. Modulation of hepatitis C virus quasispecies heterogeneity by interferon-alpha and ribavirin. J Viral Hepat 1997;4:99-106
15. Canobio S, Guilbert CM, Troesch M, et al. Differing patterns of liver disease progression and hepatitis C virus (HCV) quasispecies evolution in children vertically coinfected with HCV and human immunodeficiency virus type 1. J Clin Microbiol 2004;42:4365-4369
16. Ishii T, Ohto H, Takeuchi C, et al. Evolution in the hypervariable region of the hepatitis C virus in two infants infected by mother-to-infant transmission. Pediatr Int 2005;47:278-285
17. Farci P, Quinti I, Farci S, et al. Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively. Proc Natl Acad Sci USA 2006;103:8475-8480
18. Caudai C, Battiata M, Riccardi MP, et al. Vertical transmission of the hepatitis C virus to infants of antihuman immunodeficiency virus-negative mothers: molecular evolution of hypervariable region 1 in prenatal and perinatal or postnatal infections. J Clin Microbiol 2003;41:3955-3959
19. Lau JYN, Davis GL, Prescott LE, et al. Distribution of hepatitis C virus genotypes determined by line probe assay in patients with chronic hepatitis C seen at tertiary referral centers in the United States. Ann Intern Med 1996;124:868-876
20. Jara P, Resti M, Hierro L, et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003;36:275-280
21. Wirth S, Lang T, Gehring S, Gerner P. Recombinant alfa-interferon plus ribavirin therapy in children and adolescents with chronic hepatitis C. Hepatology 2002;36:1280-1284
22. González-Peralta RP, Kelly DA, Haber Bet alfor the International Pediatric Hepatitis C Therapy Group. Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: efficacy, safety, and pharmacokinetics. Hepatology 2005;42:1010-1018
23. Jacobson KR, Murray K, Zellos A, Schwarz KB. An analysis of published trials of interferon monotherapy in children with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2002;34:52-58
24. Jonas MM, Ott MJ, Nelson SP, et al. Interferon-alpha treatment of chronic hepatitis C virus infection in children. Pediatr Infect Dis J 1998;17:241-246
25. Matsuoka S, Tatara K, Hayabuchi Y, et al. Serologic, virologic, and histologic characteristics of chronic phase hepatitis C virus disease in children infected by transfusion. Pediatrics 1994;94:919-922
26. Garcia-Monzon C, Jara P, Fernandez-Bermejo M, et al. Chronic hepatitis C in children: a clinical and immunohistochemical comparative study with adult patients. Hepatology 1998;28:1696-1701
27. Brass V, Moradpour D, Blum HE. Molecular virology of hepatitis C virus: 2006 update. Int J Med Sci 2006;3:29-34
28. Lindenbach BD, Rice CM. Unraveling hepatitis C virus replication from genome to function. Nature 2005;436:933-938
29. Evans MJ, von Hahn T, Tscherne DM, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007;446:801-805
30. Cocquerel L, Voisset C, Dubuisson J. Hepatitis C virus entry: potential receptors and their biological functions. J Gen Virol 2006;87:1075-1084
31. Spahn CM, Kieft JS, Grassucci RA, et al. Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit. Science 2001;291:1959-1962
32. Gosert R, Egger D, Lohmann V, et al. Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 2003;77:5487-5492
33. Quinkert D, Bartenschlager R, Lohmann V. Quantitative analysis of the hepatitis C virus replication complex. J Virol 2005;79:13594-13605
34. Sakai A, Claire MS, Faulk K, et al. The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci USA 2003;100:11646-11651
35. Yi M, Ma Y, Yates J, Lemon SM. Compensatory mutations in E1, p7, NS2, and NS3 enhance yields of cell culture-infectious intergenotypic chimeric hepatitis C virus. J Virol 2007;81:629-638
36. Haqshenas G, Mackenzie JM, Dong X, Gowans EJ. Hepatitis C virus p7 protein is localized in the endoplasmic reticulum when it is encoded by a replication-competent genome. J Gen Virol 2007;88:134-142
37. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy. Science 1998;282:103-107
38. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999;341:556-562
39. Bortolotti F, Jorio R, Resti M, et al. Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period. J Hepatol 2007;46:783-790
40. Roberts EA, Yeung L. Maternal-infant transmission of hepatitis C virus infection. Hepatology 2002;36(suppl 1):S106-S113
41. European Paediatric Hepatitis C Virus Network. A significant sex - but not elective cesarean section - effect on mother-to-child transmission of hepatitis C virus infection. J Infect Dis 2005;192:1872-1879
42. Dore GJ, Kaldor JM, McCaughan GW. Systematic review of role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. BMJ 1997;315:333-337
43. Pappalardo BL. Influence of maternal human immunodeficiency virus (HIV) co-infection on vertical transmission of hepatitis C virus (HCV): a meta-analysis. Int J Epidemiol 2003;32:727-734
44. Gibb DM, Goodall RL, Dunn DT, et al. Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet 2000;356:904-907
45. Ferrero S, Lungaro P, Bruzzone BM, Gotta C, Bentivoglio G, Ragni N. Prospective study of mother-to-infant transmission of hepatitis C virus: a 10-year survey (1990-2000). Acta Obstet Gynecol Scand 2003;82:229-234
46. Giacchino R, Tasso L, Timitilli A, et al. Vertical transmission of hepatitis C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C virus-seropositive mothers. J Pediatr 1998;132:167-169
47. Okamoto M, Nagata I, Murakami J, et al. Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody. J Infect Dis 2000;182:1511-1514
48. Resti M, Azzari C, Mannelli F, et al. Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. Tuscany Study Group on Hepatitis C Virus Infection. BMJ 1998;317:437-441
49. Steininger C, Kundi M, Jatzko G, Kiss H, Lischka A, Holzmann H. Increased risk of mother-to-infant transmission of hepatitis C virus by intrapartum infantile exposure to maternal blood. J Infect Dis 2003;187:345-351
50. Tajiri H, Miyoshi Y, Funada S, et al. Prospective study of mother-to-infant transmission of hepatitis C virus. Pediatr Infect Dis J 2001;20:10-14
51. Zanetti AR, Tanzi E, Romano L, et al. A prospective study on mother-to-infant transmission of hepatitis C virus. Intervirology 1998;41:208-212
52. Azzari C, Resti M, Moriondo M, Ferrari R, Lionetti P, Vierucci A. Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection. Blood 2000;96:2045-2048
53. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology 2000;31:751-755
54. Paccagnini S, Principi N, Massironi E, et al. Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population. Pediatr Infect Dis J 1995;14:195-199
55. Resti M, Azzari C, Galli L, et al. Maternal drug use is a preeminent risk factor for mother-to-child hepatitis C virus transmission: results from a multicenter study of 1372 mother-infant pairs. J Infect Dis 2002;185:567-572
56. European Paediatric Hepatitis C Virus Network. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. BJOG 2001;108:371-377
57. McIntyre PG, Tosh K, McGuire W. Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. Cochrane Database Syst Rev 2006;(4):CD005546
58. Pembrey L, Newell ML, Tovo PA. The management of HCV infected pregnant women and their children. European Paediatric HCV Network. J Hepatol 2005;43:515-525
59. Davies G, Wilson RD, Desilets V, et al. Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus. J Obstet Gynaecol Can 2003;25:145-152
60. Mok J, Pembrey L, Tovo PA, Newell ML. When does mother to child transmission of hepatitis C virus occur? Arch Dis Child Fetal Neonatal Ed 2005;90:F156-F160
61. Kumar RM, Shahul S. Role of breast-feeding in transmission of hepatitis C virus to infants of HCV-infected mothers. J Hepatol 1998;29:191-197
62. Lin HH, Kao JH, Hsu HY, et al. Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers. J Pediatr 1995;126:589-591
63. Delia Bella S, Riva A, Tanzi E, et al. Hepatitis C virus-specific reactivity of CD4 + -lymphocytes in children born from HCV-infected women. J Hepatol 2005;43:394-402
64. Martinetti M, Pacati I, Daielli C, Salvaneschi L, Maccabruni A. Critical role of Val/Gly86 HLA-DRB dimorphism in the neonatal resistance or susceptibility to maternal hepatitis C virus infection. Pediatr Infect Dis J 1997;16:1001-1002
65. Mast EE, Hwang LY, Seto DS, et al. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis 2005;192:1880-1889
66. Polywka S, Pembrey L, Tovo PA, Newell ML. Accuracy of HCV-RNA PCR tests for diagnosis or exclusion of vertically acquired HCV infection. J Med Virol 2006;78:305-310
67. Resti M, Jara P, Hierro L, et al. Clinical features and progression of perinatally acquired hepatitis C virus infection. J Med Virol 2003;70:373-377
68. Jara P, Resti M, Hierro L, et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003;36:275-280
69. 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
70. Casiraghi MA, De Paschale M, Romano L, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology 2004;39:90-96
71. McDiarmid SV, Anand RSPLIT Research Group. Studies of pediatric liver transplantation (SPLIT): a summary of the 2003 annual report. Clin Transpl 2003:119-130
72. Rumbo C, Fawaz RL, Emre SH, et al. Hepatitis C in children: a quaternary referral center perspective. J Pediatr Gastroenterol Nutr 2006;43:209-216
73. González-Peralta RP, Langham MR, Mohan P, Colombani PM, Alford MK, Schwarz KB. Hepatocellular carcinoma in two adolescents with chronic hepatitis C virus infection. J Pediatr Gastroenterol Nutr 2003;37:380 (Abstract)
74. 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;41:1431-1437
75. Shneider BL, González-Peralta RP, Roberts EA. Controversies in the management of pediatric liver diseases: hepatitis B, C and NAFLD. Hepatology 2006;44:1344-1354
76. Feld JJ, Hoofnagle JH. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 2005;436:967-972
77. de Veer MJ, Holko M, Frevel M, et al. Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 2001;69:912-920
78. Sen GC. Viruses and interferons. Annu Rev Microbiol 2001;55:255-281
79. Shindo M, Di Bisceglie AM, Cheung L, et al. Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C. Ann Intern Med 1991;115:700-704
80. Davis GL. Treatment of acute and chronic hepatitis C. Clin Liver Dis 1997;1:615-630
81. Jacobson KR, Murray K, Zellos A, Schwarz KB. An analysis of published trials of interferon monotherapy in children with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2002;34:52-58
82. Davis GL, Esteban-Mur R, Rustgi V, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. N Engl J Med 1998;339:1493-1499
83. McHutchison JG, Gordon SC, Schiff ER, 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;339:1485-1492
84. Christensson B, Wiebe T, Akesson A, Widell A. Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission. Clin Infect Dis 2000;30:585-586
85. Lackner H, Moser A, Deutsch J, et al. Interferon-alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy. Pediatrics 2000;106:E53-E56
86. Wirth S, Lang T, Gehring S, Gerner P. Recombinant alfa-interferon plus ribavirin therapy in children and adolescents with chronic hepatitis C. Hepatology 2002;36:1280-1284
87. González-Peralta RP, Glue P, Hodik M, Davis GL, Lau JYN. Single-dose pharmacokinetics of interferon alfa2b in children with chronic hepatitis C. Hepatology 1999;30:264A
88. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965
89. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-982
90. Schwarz KB, Mohan P, Narkewicz MR, et al. The safety, efficacy, and pharmacokinetics of peginterferon alfa-2b (40kD) in children with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2006;43:499-505
91. Wirth S, Pieper-Boustani H, Lang T, et al. Peginterferon alfa-2b plus ribavirin treatment in children and adolescents with chronic hepatitis C. Hepatology 2005;41:1013-1018
92. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003;38:645-652
93. Polifka JE, Friedman JM. Developmental toxicity of ribavirin/IFalpha combination therapy: is the label more dangerous than the drugs? Birth Defects Res A Clin Mol Teratol 2003;67:8-12
94. Barlow CF, Priebe CJ, Mulliken JB, et al. Spastic diplegia as a complication of interferon alfa-2a treatment of hemangiomas of infancy. J Pediatr 1998;132:527-530
95. Murray KF, Barton B, González-Peralta RPet alfor the PEDS-C Clinical Research Network. Development of a multi-center, randomized controlled trial for children with chronic hepatitis C (PEDS-C). J Pediatr Gastroenterol Nutr 2005;41:524 (Abstract)
96. U.S. Code of Federal Regulations. Title 21, Food and Drugs: 314.55 and 601.27.
97. Balan V, Nelson DR, Sulkowski MS, et al. Phase I/II study evaluating escalating subcutaneous doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antivir Ther 2006;11:35-45
98. Bain VG, Kaita KD, Yoshida EM, et al. A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 2006;44:671-678
99. Gish RG. Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother 2006;57:8-13
100. Gish RG, Arora S, Reddy KR, et al. Virological response and safety outcomes in therapy-naive patients treated for chronic hepatitis C with taribavirin or ribavirin in combination with pegylated interferon alfa-2a: a randomized, phase 2 study. J Hepatol 2007;47:51-59
101. Benhamou Y, Pockros P, Rodriquez-Torres M, et al. The safety and efficacy of viramidine plus pegylated interferon alfa-2b versus ribavirin plus pegylated interferon alfa-2b in therapy-naive patients infected with HCV: phase 3 results. J Hepatol 2006;44(suppl 2):S273
102. McHutchison JG, Shiffman ML, Cheung RC, et al. A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C. Antivir Ther 2005;10:635-643
103. Pockros PJ, Pessoa MG, Diago M, et al. Combination of levovirin and peginterferon alfa-2a fails to generate virological response comparable to ribavirin and peginterferon alfa-2a in patients with chronic hepatitis C. Hepatology 2004;40(suppl):391A
104. Welbourn S, Green R, Gamache I, et al. Hepatitis C virus NS2/3 processing is required for NS3 stability and viral RNA replication. J Biol Chem 2005;280:29604-29611
105. Grakoui A, McCourt DW, Wychowski C, Feinstone SM, Rice CM. Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J Virol 1993;67: 2832-2843
106. Foy E, Li K, Wang C, et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 2003;300:1145-1148
107. Lemon SM, Yi M, Li K. "Strong reasons make strong actions" - the antiviral efficacy of NS3/4A protease inhibitors. Hepatology 2005;41:671-674
108. Hinrichsen H, Benhamou Y, Wedemeyer H, et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 2004;127:1347-1355
109. Reesink HW, Zeuzem S, Weegink CJ, et al. Final results of a phase lb, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. Hepatology 2005;42:234A
110. Reesink HW, Zeuzem S, Weegink CJ, et al. Initial results of a 14-day study of the hepatitis C virus inhibitor VX-950, in combination with peginterferon-alfa 2a. J Hepatol 2006;44(suppl 2):S272
111. Lawitz E, Rodriguez-Torres M, Muir A, et al. 28 days of the hepatitis C protease inhibitor VX-950, in combination with peg-interferon-alfa-2a and ribavirin, is well-tolerated and demonstrates robust antiviral effects. Gastroenterology 2006;130(suppl 2):A686
112. Zeuzem S, Sarrazin C, Rouzier R, et al. Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (peg-IFN-α). Hepatology 2005;42:233A
113. Zeuzem S, Sarrazin C, Wagner F, et al. Combination therapy with the HCV protease inhibitor, SCH 503034, plus PEG-Intron in hepatitis C genotype-1 PEG-Intron non-responders: phase Ib results. Hepatology 2005;42: 276A
114. Gale M, Foy E. Evasion of intracellular host defense by hepatitis C virus. Nat Med 2005;436:939-945
115. Zeuzem S, Sarrazin C, Rouzier R, et al. Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (peg-IFN-α). Hepatology 2005;42:233A
116. Kieffer T, Sarrazin C, Miller J, et al. Combination of telaprevir (VX-950) and PEG-IFN-alfa suppressed both wild-type virus and resistance variants in HCV genotype 1-infected patients in a 14-day phase 1B study. Hepatology 2006;44:222A
117. Kieffer T, Sarrazin C, Battels D, et al. Wild-type HCV NS3 protease re-emerges during follow-up after 14 days of dosing with VX-950 in patients with genotype 1 HCV. J Hepatol 2006;44(suppl 2):S7
118. O'Brien C, Godofsky E, Roriguez-Torres M, et al. Randomized trial of valopicitabine (NM283) alone or with PEG-interferon vs. retreatment with PEG-interferon plus ribavirin (PEGIFN/RBV) in hepatitis C patients with previous non-response to PEGIFN.RBV: first interim results. Hepatology 2005;42:232A
119. Dieterich D, Lawitz E, Nguyen T, et al. Early clearance of HCV RNA with valopicitabine (NM283) plus peginterferon in treatment-naive patients with HCV-1 infection: first results from a phase IIb trial. J Hepatol 2006;44(suppl 2):S271-S272
120. Roberts S, Cooksley G, Dore G, et al. Results of a phase 1B multiple dose study of R1626 a novel nucleoside analog targeting HCV polymerase in chronic HCV genotype 1 patients. Hepatology 2006;44:692A
121. Chandra P, Raible D, Harper D, Speth J, Villano S, Bichier G. Antiviral activity of the non-nucleoside polymerase inhibitor HCV-796 in patients with chronic hepatitis C virus: preliminary results from a randomized, double-blind, placebo-controlled, ascending multiple dose study. Gastroenterology 2006;130(suppl 2):A748