European Journal of Medical Research | |
New hepatitis C therapies in clinical development | |
Christoph Sarrazin1  Johannes Vermehren1  | |
[1] Medizinische Klinik 1, Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany | |
关键词: cyclophilin inhibitor; NS5A inhibitor; polymerase inhibitor; protease inhibitor; direct-acting antivirals; chronic hepatitis C; | |
Others : 825095 DOI : 10.1186/2047-783X-16-7-303 |
|
received in 2011-01-15, accepted in 2011-01-20, 发布年份 2011 | |
【 摘 要 】
With the current standard of care for the treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, sustained virologic response rates can be achieved in approximately 50% of patients only.
Improved understanding of the viral life cycle has led to the identification of numerous potential targets for novel, direct-acting antiviral compounds. Inhibitors of the NS3/4A protease are currently the most advanced in clinical development. Recently completed phase 3 studies of the two protease inhibitors telaprevir and boceprevir, each given in combination with standard of care, yielded sustained virologic response rates in the range of 66-75% in treatment-naive patients and 59-66% in treatment-experienced patients with HCV genotype 1 infection. Studies of second-generation protease inhibitors, with the potential advantage of improved potency, drug metabolism and pharmacokinetics profile, are already underway.
Inhibitors of the HCV NS5A protein and NS5B polymerase are potentially active across different HCV genotypes and have shown promising antiviral efficacy in early clinical studies. Other emerging mechanisms include silymarin components and inhibitors of cell proteins required for HCV replication.
While improved formulations of current HCV therapies are also being developed, future hopes lie on the combination of direct-acting antivirals with the eventual possibility of interferon-free treatment regimens.
【 授权许可】
2011 I. Holzapfel Publishers
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140713054449637.pdf | 1315KB | download | |
Figure 2. | 23KB | Image | download |
Figure 1. | 25KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]World Health Organization, Hepatitis C[http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index4.html] webcite accessed on 01.12.2010
- [2]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.
- [3]Hadziyannis SJ, Sette H, Morgan TR, et al.: Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004, 140:346-355.
- [4]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.
- [5]Zeuzem S, Hultcrantz R, Bourliere M, et al.: Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 2004, 40:993-999.
- [6]Kim JL, Morgenstern KA, Lin C, et al.: Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 1996, 87:343-355.
- [7]Lohmann Y, Korner F, Koch J, et al.: Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999, 285:110-113.
- [8]Moradpour D, Penin F, Rice CM: Replication of hepatitis C virus. Nat Rev Microbiol 2007, 5:453-463.
- [9]Wakita T, Pietschmann T, Kato T, et al.: Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 2005, 11:791-796.
- [10]Lamarre D, Anderson PC, Bailey M, et al.: An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 2003, 426:186-189.
- [11]Forestier N, Reesink HW, Weegink CJ, et al.: Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007, 46:640-648.
- [12]Lawitz E, Rodriguez-Torres M, Muir AJ, et al.: Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients. J Hepatol 2008, 49:163-169.
- [13]Reesink HW, Zeuzem S, Weegink CJ, et al.: Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 2006, 131:997-1002.
- [14]Kieffer TL, Sarrazin C, Miller JS, et al.: Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 2007, 46:631-639.
- [15]Sarrazin C, Kieffer TL, Bartels D, et al.: Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007, 132:1767-1777.
- [16]Hezode C, Forestier N, Dusheiko G, et al.: Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009, 360:1839-1850.
- [17]McHutchison JG, Everson GT, Gordon SC, et al.: Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009, 360:1827-1838.
- [18]McHutchison JG, Manns MP, Muir AJ, et al.: Telaprevir for previously treated chronic HVR infection. N Engl J Med 2010, 362:1292-1303.
- [19]Marcellin P, Forns X, Goeser T, et al.: Telaprevir Is Effective Given Every 8 or 12 Hours With Ribavirin and Peginterferon Alfa-2a or -2b to Patients With Chronic Hepatitis C. Gastroenterology 2010, in press.
- [20]Benhamou Y, Moussalli J, Ratziu Y, et al.: Activity of telaprevir monotherapy or in combination with peginterferon-alfa-2a and ribavirin in treatment-naive genotype 4 hepatitis-C-patients: final results of study C210. Hepatology 2010, 52:719A.
- [21]Foster GR, Hezode C, Bronowicki JP, et al.: Activity of telaprevir alone or in combination with peginterferon alfa-2a and ribavirin in treatment-naive genotype 2 and 3 hepatitis-C patients: final results of study C209. J Hepatol 2010, 52:S27.
- [22]Jacobson IM, McHutchison JG, Dusheiko G, et al.: Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment-naive patients: final results of phase 3 ADVANCE study. Hepatology 2010, 52:427A.
- [23]Vertex Pharmaceuticals Inc: 65% of people whose prior treatment for hepatitis C was unsuccessful achieved SVR (viral cure) with telaprevir-based therapy in phase 3 REALIZE study. [http://http: //investors.vrtx.com/releasedetail.cfm?ReleaseID_505239] webcitePress Release 2010. accessed on 01.12.2010
- [24]Sherman KE, Flamm SL, Afdhal NH, et al.: Telaprevir in combination with peginterferon alfa-2a and ribavirin for 24 or 48 weeks in treatment-naive genotype 1 HVR patients who achieved an extended rapid viral response: final results of phase 3 ILLUMINATE study. Hepatology 2010, 52:401A.
- [25]Zeuzem S, Sulkowski MS, Zoulim F, et al.: Long-term follow-up of patients with chronic hepatitis C treated with telaprevir in combination with peginterferon alfa-2a and ribavirin: interim analysis of the extend study. Hepatology 2010, 52:436A.
- [26]Susser S, Forestier N, Yermehren J, et al.: Decline of detectable resistance mutations within the HCV NS3 protease quasispecies during long-term follow-up after treatment with telaprevir. J Hepatol 2010, 52:S300.
- [27]Sarrazin C, Rouzier R, Wagner F, et al.: SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 2007, 132:1270-1278.
- [28]Susser S, Welsch C, Wang Y, et al.: Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology 2009, 50:1709-1718.
- [29]Vermehren J, Susser S, Karey U, et al.: Clonal analysis of mutations selected in the HCV NS3 protease domain of genotype 1 non-responders sequentially treated with boceprevir (SCH503034) and/or pegylated interferon alfa-2b (PEG-IFN alfa-2b). Hepatology 2009, 50:1040A.
- [30]Kwo PY, Lawitz EJ, McCone J, et al.: Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet 2010, 376:705-716.
- [31]Schiff E, Poordad F, Jacobson I, et al.: Boceprevir combination therapy in null responders: Response dependent on interferon resonsiveness. J Hepatol 2008, 48:S46.
- [32]Bacon BR, Gordon SC, Lawitz E, et al.: HCV RESPOND-2 final results: High sustained virologic response among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir plus pegintron (peginterferon alfa-2b)/ribavirin. Hepatology 2010, 52:430A.
- [33]Poordad F, McCone J, Bacon BR, et al.: Boceprevir (BOC) combined with peginterferon alfa-2b/ribavirin (P/R) for treatment-naive patients with hepatitis C virus (HVR) genotype (G) 1: SPRINT-2 final results. Hepatology 2010, 52:402A.
- [34]Berg T, Dieterich DT, Lalezari JP, et al.: Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alfa 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin. Hepatology 2010, 52:704A.
- [35]Brainard DM, Petry A, van Dyck K, et al.: Safety and antiviral activity of MK-5172, a novel HVR NS3/4A protease inhibitor with potent activity against known resistance mutants, in genotype 1 and 3 HCV-infected patients. Hepatology 2010, 52:706A.
- [36]de Bruijne J, Bergmann JF, Reesink HW, et al.: Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients. Hepatology 2010, 52:1590-9.
- [37]Detishin Y, Haazen W, Robison H, et al.: Virological response, safety, and pharmacokinetic profile following single-and multiple-dose administration of ACH-0141625 protease inhibitor to healthy volunteers and HCV genotype-1 patients. J Hepatol 2010, 52:S468.
- [38]Forestier N, Larrey D, Guyader D, et al.: Treatment of chronic hepatitis C Patients with the NS3/4A protease inhibitor danoprevir (ITMN-191/RG7227) leads to robust reductions in viral RNA: a phase 1b multiple ascending dose study. J Hepatol 2010, in press.
- [39]Fried MW, Buti M, Dore GJ, et al.: Efficacy and safety of TMC435 in combination with peginterferon alfa-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study. Hepatology 2010, 52:403A.
- [40]Goldwater R, DeMicco MP, Zong J, et al.: Safety, pharmacokinetics, and antiviral activity of single oral doses of the HCV NS3 protease inhibitor GS 9256. Hepatology 2010, 52:717A.
- [41]Hotho D, de Bruijne J, O'Farrell AM, et al.: Accelerated clinical trial design to assess the safety, tolerability and anti-viral activity of PHX1766, a novel HCV NS3/4A protease inhibitor, in healthy volunteers and chronic hepatitis C patients. Hepatology 2009, 50:1031A.
- [42]Lawitz E, Hill JM, Marbury TC, et al.: Three-day, dose-ranging study of the HCV NS3 protease inhibitor GS-9451. Hepatology 2010, 52:714A.
- [43]Lawitz E, Gaultier F, Poordad F, et al.: 4-week virologic response and safety of ABT-450 given with low-dose ritonavir (ABT-450/r) in combination with pegylated interferon alpha-2a and ribavirin (SOC) after 3-day monotherapy in genotype 1 (GT1) HCV-infected treatment-naive subjects. Hepatology 2010, 52:878A.
- [44]Manns MP, Gane EJ, Rodriguez-Torres M, et al.: Sustained viral response (SVR) rates in genotype 1 treatment-naive patients with chronic hepatitis C (CHC) infection treated with vaniprevir (MK-7009), a NS3/4A protease inhibitor, in combination with pegylated interferon alfa-2a and ribavirin for 28 days. Hepatology 2010, 52:361A.
- [45]Pasquinelli C, Eley T, Villegas C, et al.: Safety, tolerability, pharmacokinetics and antiviral activity following single- and multiple-dose administration of BMS-650032, a novel HCV NS3 inhibitor, in subjects with chronic genotype 1 HCV infection. Hepatology 2009, 50:411A.
- [46]Terrault NA, Cooper C, Balart LA, et al.: Phase II randomised, partially-blind, parallel-group study of oral danoprevir (RG7227) with PegIFNalfa-2a (PEGASYS) plus ribavirin in treatment-naive genotype 1 patients with CHC: results of planned week 12 interim analysis of the ATLAS study. Hepatology 2010, 52:335A.
- [47]Sarrazin C, Zeuzem S: Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 2010, 138:447-462.
- [48]Lesburg CA, Cable MB, Ferrari E, et al.: Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol 1999, 6:937-943.
- [49]Lawitz E, Nguyen T, Younes Z, et al.: Clearance of HCV RNA with valopicitabine (NM283) plus peg-interferon in treatment-naive patients with HCV-1 infection: Results at 24 and 48 weeks. J Hepatol 2007, 46:S9.
- [50]Pockros PJ, Nelson D, Godofsky E, et al.: R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin. Hepatology 2008, 48:385-397.
- [51]Roberts SK, Cooksley G, Dore GJ, et al.: Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C. Hepatology 2008, 48:398-406.
- [52]Jensen DM, Wedemeyer H, Herring RW, et al.: High rates of early viral response, promising safety profile and lack of resistance-related breakthrough in HCV GT 1/4 patients treated with RG7128 plus PEGIFN alfa-2a (40KD)/RBV: planned week 12 interim analysis from the propel study. Hepatology 2010, 52:360A.
- [53]Lawitz E, Lalezari JP, Rodriguez-Torres M, et al.: High rapid virologic response (RVR) with PSI-7977 qd plus PEG-IFN/ RBV in a 28-day phase 2a trial. Hepatology 2010, 52:706A.
- [54]Pharmasset Inc: Positive preliminary antiviral data with PSI-938 for the treatment of hepatitis C. [http://htpp: //investor.pharmasset.com/releasedetail.cfm?Relea seID = 531337] webcitePress Release 2010. accessed on 01.12.2010
- [55]Brainard DM, Anderson MS, Petry A, et al.: Safety and antiviral activity of NS5B polymerase inhibitor MK-3281 in treatment-naive genotype 1a, 1b and 3 HCV-infected patients. Hepatology 2009, 50:1026A.
- [56]Erhardt A, Deterding K, Benhamou Y, et al.: Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment. Antivir Ther 2009, 14:23-32.
- [57]Larrey DG, Benhamou Y, Lohse AW, et al.: BI 207127 is a potent HCV RNA polymerase inhibitor during 5 days monotherapy in patients with chronic hepatitis C. Hepatology 2009, 50:1044A.
- [58]Larrey DG, Lohse AW, de Ledinghen V, et al.: 4 week therapy with the non-nucleoside polymerase inhibitor BI207127 in combination with peginterferon-alfa2a and ribavirin in treatment naive and treatment experienced chronic HCV GT1 patients. J Hepatol 2010, 52:S466.
- [59]Jacobson IM, Pockros PJ, Lalezari J, et al.: Virologic response rates following 4 weeks of filibuvir in combination with pegylated interferon alfa-2a and ribavirin in chronically-infected HCV genotype-1 patients. J Hepatol 2010, 52:S465.
- [60]Cooper C, Lawitz EJ, Ghali P, et al.: Evaluation of VCH-759 monotherapy in hepatitisC infection. J Hepatol 2009, 51:39-46.
- [61]Lawitz E, Cooper C, Rodriguez-Torres M, et al.: Safety, tolerability and antiviral activity of VCH-916, a novel non-nucleoside HCV polymerase inhibitor in patients with chronic HCV genotype-1 infection. J Hepatol 2009, 50:S37.
- [62]Rodriguez-Torres M, Lawitz E, Conway B, et al.: Safety and antiviral activity of the HCV non-nucleoside polymerase inhibitor VX-222 in treatment-naive genotype 1 HCV-infected patients. J Hepatol 2010, 52:S14.
- [63]Lawitz E, Rodriguez-Torres M, Rustgi VK, et al.: Safety and antiviral activity of ANA598 in combination with pegylated interferon alfa-2a plus ribavirin in treatment-naive genotype-1 chronic HCV patients. Hepatology 2010, 52:334A.
- [64]Rodriguez-Torres M, Lawitz E, Cohen D, et al.: Treatmentnaive, HCV genotype 1-infected subjects show significantly greater HCV RNA decreases when treated with 28 days of ABT-333 plus peginterferon and ribavirin compared to peginterferon and ribavirin alone. Hepatology 2009, 50:5A.
- [65]Kneteman NM, Howe AY, Gao T, et al.: HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology 2009, 49:745-752.
- [66]Harris J, Bae A, Sun SC, et al.: Antiviral response and resistance analysis of treatment-naive HCV infected subjects receiving single and multiple doses of GS-9190. Hepatology 2010, 52:722A.
- [67]de Bruijne J, van de Wetering de Rooij J, van Vliet AA, et al.: Phase I study in healthy volunteers and patients with IDX375, a novel non-nucleoside HCV polymerase inhibitor. Hepatology 2010, 52:1219A.
- [68]Gao M, Nettles RE, Belema M, et al.: Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 2010, 465:96-100.
- [69]Pol S, Everson GT, Ghalib R, et al.: Once-daily NS5A inhibitor (BMS-790052) plus peginterferon-alpha-2a and ribavirin produces high rates of extended rapid virologic response in treatment-naive HCV-genotype 1 subjects: phase 2a trial. J Hepatol 2010, 52:S462.
- [70]Colonno R, Peng E, Bencsik M, et al.: Identification and characterization of PPI-461, a potent and selective HCV NS5A inhibitor with activity against all HCV genotypes. J Hepatol 2010, 52:S14.
- [71]Gane EJ, Foster GR, Cianciara J, et al.: Antiviral activity, pharmakokinetics, and tolerability of AZD7295, a novel NS5A inhibitor, in a placebo-controlled multiple ascending dose study in HCV genotype 1 and 3 patients. J Hepatol 2010, 52:S464.
- [72]Nettles R, Wang X, Quadri S, et al.: BMS-824393 is a potent hepatitis C virus NS5A inhibitor with substantial antiviral activity when given as monotherapy in subjects with chronic G1 HCV infection. Hepatology 2010, 52:1203A.
- [73]Witthoeft T, Hueppe D, John C, et al.: Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study. J Viral Hepat 2010, 17:459-468.
- [74]Gane EJ, Roberts SK, Stedman CA, et al.: Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010, 376:1467-1475.
- [75]Zeuzem S, Buggisch P, Agarwal A, et al.: Dual, triple, and quadruple combination treatment with a protease inhibitor (GS-9256) and a polymerase inhibitor (GS-9190) alone and in combination with ribavirin (RBV) or PegIFN/RBV for up to 28 days in treatment naive, genotype 1 HCV subjects. Hepatology 2010, 52:400A.
- [76]Zeuzem S, Asselah T, Angus PW, et al.: Strong antiviral activity and safety of IFN-sparing treatment with the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127 and ribavirin in patients with chronic hepatitis C. Hepatology 2010, 52:876A.
- [77]Lok AS, Gardiner DF, Lawitz E, et al.: Combination therapy with BMS-790052 and BMS-650032 alone or with PEGIFN/RBV results in undetectable HCV RNA through 12 weeks of therapy in HCV genotype 1 null responders. Hepatology 2010, 52:877A.
- [78]Rong L, Dahari H, Ribeiro RM, et al.: Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010, 2:30ra32.
- [79]Flisiak R, Feinman SY, Jablkowski M, et al.: The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology 2009, 49:1460-1468.
- [80]Horban A, Berak H, Kolakowska-Rzadzka A, et al.: Sustained virological response after 4-week treatment with debio 025 monotherapy or coadministered with PEG-IFN alpha 2a in HCV genotype 1 and 3 patients. J Hepatol 2010, 52:S294.
- [81]Coelmont L, Hanoulle X, Chatterji U, et al.: DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A. PLoS One 2010, 5:e13687.
- [82]Hopkins S, Heuman D, Gavis E, et al.: Safety, plasma pharmakokinetics, and anti-viral activity of SCY-635 in adult patients with chronic hepatitis C virus infection. J Hepatol 2009, 50:S36.
- [83]Hopkins S, Mosier S, Harris R, et al.: Resistance selection following 15 days of monotherapy with SCY-635 a non-immunosuppressive cyclophilin inhibitor with potent anti-HCV activity. J Hepatol 2010, 52:S15.
- [84]Gazak R, Walterova D, Kren V: Silybin and silymarin--new and emerging applications in medicine. Curr Med Chem 2007, 14:315-338.
- [85]Ahmed-Belkacem A, Ahnou N, Barbotte L, et al.: Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Gastroenterology 2010, 138:1112-1122.
- [86]Wagoner J, Negash A, Kane OJ, et al.: Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 2010, 51:1912-1921.
- [87]Ferenci P, Scherzer TM, Kerschner H, et al.: Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008, 135:1561-1567.
- [88]Biermer M, Schlosser B, Fülöp B, et al.: A short course of high-dose intravenous silibinin as rescue treatment for hepatitis C patients with incomplete virologic response to peginterferon alfa/ribavirin treatment. Hepatology 2010, 52:798A.
- [89]Benhamou Y, Afdhal NH, Nelson DR, et al.: A phase III study of the safety and efficacy of viramidine versus ribavirin in treatment-naive patients with chronic hepatitis C: ViSER1 results. Hepatology 2009, 50:717-726.
- [90]Marcellin P, Gish RG, Gitlin N, et al.: Safety and efficacy of viramidine versus ribavirin in ViSER2: randomized, double-blind study in therapy-naive hepatitis C patients. J Hepatol 2010, 52:32-38.
- [91]Poordad F, Lawitz E, Shiffman ML, et al.: Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C. Hepatology 2010, 52:1208-1215.
- [92]Nelson DR, Benhamou Y, Chuang WL, et al.: Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3. Gastroenterology 2010, 139:1267-1276.
- [93]Zeuzem S, Sulkowski MS, Lawitz EJ, et al.: Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 1. Gastroenterology 2010, 139:1257-1266.
- [94]Long WA, Takov D, Tchernev K, et al.: Q2week controlled-release-interferon-alpha2b+ribavirin reduces flu-like symptoms >50% and provides equivalent efficacy in comparison to weekly pegylated-interferon-alpha2b+ribavirin in treatment-naive-genotype-1-chronic-hepatitis C: results from EMPOWER, a randomized-open-label-12-week-comparison in 133 patients. J Hepatol 2010, 52:S467-S467.
- [95]Bacon BR, Shiffman ML, Mendes F, et al.: Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology 2009, 49:1838-1846.
- [96]Muir AJ, Shiffman ML, Zaman A, et al.: Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 2010, 52:822-832.
- [97]Seden K, Back D, Khoo S: New directly acting antivirals for hepatitis C: potential for interaction with antiretrovirals. J Antimicrob Chemother 2010, 65:1079-1085.