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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 9
Sep.  2016
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Article Contents

Mechanism of action of direct-acting antiviral agents in treatment of chronic hepatitis C

DOI: 10.3969/j.issn.1001-5256.2016.09.013
  • Published Date: 2016-09-20
  • With the development and launch of direct- acting antiviral agents( DAAs) in the world in recent years,therapeutic regimens for chronic hepatitis C are constantly evolving. DAAs will also be launched in China in the near future. DAAs mainly target at the non-structural proteins of HCV and can inhibit HCV RNA replication. This article introduces the targets,mechanism of action,and resistance characteristics of different DAAs,as well as their current research and development in China and the results of phase Ⅲ clinical studies,in order to provide a reference for combined therapeutic strategies with DAAs in the treatment for chronic hepatitis C.

     

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  • [1]World Health Organization.Guidelines for the screening,care and treatment of persons with hepatitis C infection[R].Geneva:WHO,2016.
    [2]SIEVERT W,ALTRAIF I,RAZAVI HA,et al.A systematic review of hepatitis C virus epidemiology in Asia,Australia and Egypt[J].Liver Int,2011,31(Suppl 2):61-80.
    [3]RAO H,WEI L,LOPEZ-TALAVERA JC,et al.Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection[J].J Gastroenterol Hepatol,2014,29(3):545-553.
    [4] Chinese Society of Hepatology,Chinese Society of Infectious Disease,Chinese Medical Association.The guideline of prevention and treatment for hepatitis C:a 2015 update[J].J Clin Hepatol,2015,31(12):1961-1979.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.丙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1961-1979.
    [5]GUO X,ZHAO Z,XIE J,et al.Prediction of response to pegylatedinterferon-αand ribavirin therapy in Chinese patients infected with different hepatitis C virus genotype[J].Virol J,2012,9(1):123.
    [6]HE LL,CHEN Z,CHEN Y,et al.Association between the influential factors and the effectiveness of pegylated interferon alpha-2a plus ribavirin as a combination treatment for chronic hepatitis C patients[J].Chin J Hepatol,2011,19(1):34-37.(in Chinese)何伶俐,陈竹,陈杨,等.聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的疗效及其影响因素[J].中华肝脏病杂志,2011,19(1):34-37.
    [7]MA LN,CHEN XY,CHEN J,et al.Efficacy,influencing factors and safety of PEG-INF alpha-2a(PEG-INF-2a)in the treatment of chronic hepatitis C:analysis of 89 patients[J].Chin J Exp Clin Virol,2006,20(2):42-45.(in Chinese)马丽娜,陈新月,陈杰,等.聚乙二醇干扰素治疗慢性丙型肝炎临床疗效、影响因素及安全性分析(附89例临床分析)[J].中华实验和临床病毒学杂志,2006,20(2):42-45.
    [8]LIAO XW,LING Y,LI XH,et al.Association of genetic variation in IL28B with hepatitis C treatment-induced viral clearance in the Chinese Han population[J].Antivir Ther,2011,16(2):141-147.
    [9]TSANG TY,ZEE ST,CHAN MC,et al.Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1[J].J Gastroenterol Hepatol,2010,25(4):766-771.
    [10]YU JW,WANG GQ,SUN LJ,et al.Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferonα-2a and ribavirin[J].J Gastroenterol Hepatol,2007,22(6):832-836.
    [11]ZHOU BT,FAN YM,LI DM,et al.Effectiveness of combined therapies using two types of peginterferon and ribavirin in treating chronic hepatitis C virus genotypes 1b/6a infections[J].Acta Acad Med Sin,2010,32(3):320-323.(in Chinese)周宝桐,范蕴明,李德明,等.两种聚二醇干扰素联合利巴韦林治疗1b及6a亚型慢性丙型肝炎的疗效[J].中国医学科学院学报,2010,32(3):320-323.
    [12]WEI L,ZHANG M,XU M,et al.A phase 3,open-label study of daclatasvir plus asunaprevir in Asian patients with chronic hepatitis C virus genotype 1b infection who are ineligible for or intolerant to interferon alfa therapies with or without ribavirin[J].J Gastroenterol Hepatol,2016.[Epub ahead of print]
    [13]LEE MH,YANG HI,LU SN,et al.Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases:a community-based long-term prospective study[J].J Infect Dis,2012,206(4):469-477.
    [14]ANDREONE P,COLOMBO MG,ENEJOSA JV,et al.ABT-450,ritonavir,ombitasvir,and dasabuvir achieves 97%and 100%sustained virologic response with or without ribavirin in treatmentexperienced patients with HCV genotype 1b infection[J].Gastroenterology,2014,147(2):359-365.
    [15]FELD JJ,KOWDLEY KV,COAKLEY E,et al.Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin[J].N Engl J Med,2014,370(17):1594-1603.
    [16]FERENCI P,BERNSTEIN D,LALEZARI J,et al.ABT-450/rombitasvir and dasabuvir with or without ribavirin for HCV[J].N Engl J Med,2014,370(21):1983-1992.
    [17]KOWDLEY KV,GORDON SC,REDDY KR,et al.Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis[J].N Engl J Med,2014,370(20):1879-1888.
    [18]MANNS M,POL S,JACOBSON IM,et al.All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b:a multinational,phase 3,multicohort study[J].Lancet,2014,384(9954):1597-1605.
    [19]POORDAD F,SCHIFF ER,VIERLING JM,et al.Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence[J].Hepatology,2016,63(5):1493-1505.
    [20]ZEUZEM S,JACOBSON IM,BAYKAL T,et al.Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin[J].N Engl J Med,2014,370(17):1604-1614.
    [21]AASLD/IDSA HCV Guidance Panel.Hepatitis C guidance:AASLD-IDSA recommendations for testing,managing,and treating adults infected with hepatitis C virus[J].Hepatology,2015,62(3):932-954.
    [22]European Association for the Study of Liver.EASL recommendations on treatment of hepatitis C 2015[J].J Hepatol,2015,63(1):199-236.
    [23]SCHEEL TK,RICE CM.Understanding the hepatitis C virus life cycle paves the way for highly effective therapies[J].Nat Med,2013,19(7):837-849.
    [24]FEENEY ER,CHUNG RT.Antiviral treatment of hepatitis C[J].BMJ,2014,348:g3308.
    [25]GOFFARD A,CALLENS N,BARTOSCH B,et al.Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins[J].J Virol,2005,79(13):8400-8409.
    [26]MADAN V,BARTENSCHLAGER R.Structural and functional properties of the hepatitis C virus p7 viroporin[J].Viruses,2015,7(8):4461-4481.
    [27]MORADPOUR D,PENIN F,RICE CM.Replication of hepatitis C virus[J].Nat Rev Microbiol,2007,5(6):453-463.
    [28]STEINMANN E,PENIN F,KALLIS S,et al.Hepatitis C virus p7protein is crucial for assembly and release of infectious virions[J].PLo S Pathog,2007,3(7):962-971.
    [29]BARTENSCHLAGER R,AHLBORN-LAAKE L,MOUS J,et al.Nonstructural protein 3 of the hepatitis C virus encodes a serinetype proteinase required for cleavage at the NS3/4 and NS4/5 junctions[J].J Virol,1993,67(7):3835-3844.
    [30]GALLINARI P,BRENNAN D,NARDI C,et al.Multiple enzymatic activities associated with recombinant NS3 protein of hepatitis C virus[J].J Virol,1998,72(8):6758-6769.
    [31]BRESSANELLI S,TOMEI L,ROUSSEL A,et al.Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus[J].Proc Natl Acad Sci U S A,1999,96(23):13034-13039.
    [32]BRESSANELLI S,TOMEI L,REY FA,et al.Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides[J].J Virol,2002,76(7):3482-3492.
    [33]KIM DY,AHN SH,HAN KH.Emerging therapies for hepatitis C[J].Gut Liver,2014,8(5):471-479.
    [34]PREMOLI C,AGHEMO A.Directly acting antivirals against hepatitis C virus:mechanisms of action and impact of resistant associated variants[J].Minerva Gastroenterol Dietol,2016,62(1):76-87.
    [35]ROSENQUIST,SAMUELSSON B,JOHANSSON PO,et al.Discovery and development of simeprevir(TMC435),a HCV NS3/4A protease inhibitor[J].J Med Chem,2014,57(5):1673-1693.
    [36]Mc PHEE F,SHEAFFER AK,FRIBORG J,et al.Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor asunaprevir(BMS-650032)[J].Antimicrob Agents Chemother,2012,56(10):5387-5396.
    [37]ELTAHLA AA,LUCIANI F,WHITE PA,et al.Inhibitors of the hepatitis C virus polymerase:Mode of action and resistance[J].Viruses,2015,7(10):5206-5224.
    [38]LAM AM,ESPIRITU C,BANSAL S,et al.Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus[J].Antimicrob Agents Chemother,2012,56(6):3359-3368.
    [39]DONALDSON EF,HARRINGTON PR,O'REAR JJ,et al.Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir[J].Hepatolology,2015,61(1):56-65.
    [40]LONTOK E,HARRINGTON P,HOWE A,et al.Hepatitis C virus drug resistance-associated substitutions:state of the art summary[J].Hepatolology,2015,62(5):1623-1632.
    [41]Mc PHEE D,FALK P,FRACASSO P,et al.Characterization of viral escape in HCV genotype 1-infected patients treated with BMS-791325 and pegylated interferon-alfa and ribavirin[J].J Hepatol,2012,56(2):s473.
    [42]de FRANCESCO R,MIGLIACCIO G.Challenges and successes in developing new therapies for hepatitis C[J].Nature,2005,436(7053):953-960.
    [43]GAO M,NETTLES RE,BELEMA M,et al.Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect[J].Nature,2010,465(7294):96-100.
    [44]KOHLER JJ,NETTLES JH,AMBLARD F,et al.Approaches to hepatitis C treatment and cure using NS5A inhibitors[J].Infect Drug Resist,2014,7:41-56.
    [45]AHMED A,FELMLEE DJ.Mechanisms of hepatitis C viral resistance to direct acting antivirals[J].Viruses,2015,7(12):6716-6729.
    [46]Mc PHEE F,FRIBORG J,LEVINE S,et al.Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir[J].Antimicrob Agents Chemother,2012,56(7):3670-3681.
    [47]AFDHAL N,ZEUZEM S,KWO P,et al.Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection[J].N Engl J Med,2014,370(20):1889-1898.
    [48]Gilead Sciences,Inc.Sovaldi(sofosbuvir)tablets[prescribing information][Z].Foster City,2015.
    [49]JACOBSON IM,GORDON SC,KOWDLEY KV,et al.Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options[J].N Engl J Med,2013,368(20):1867-1877.
    [50]LAWITZ E,MANQIA A,WYLES D,et al.Sofosbuvir for previously untreated chronic hepatitis C infection[J].N Engl J Med,2013,368(20):1878-1887.
    [51]NELSON DR,COOPER JN,LALEZARI JP,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[J].Hepatology,2015,61(4):1127-1135.
    [52] Center for Drug Evaluation.Announcement of applications for HCV drug registration planned to be included in priority review process[EB/OL].http://www.cde.org.cn/news.do?method=view Info Common&id=313562.(in Chinese)国家食品药品监督管理局药品评价中心.拟纳入优先审评程序HCV药物注册申请的公示[EB/OL].http://www.cde.org.cn/news.do?method=view Info Common&id=313562.
    [53]LIN TI,LENZ O,FANNING G,et al.In vitro activity and preclinical profile of TMC435350,a potent hepatitis C virus protease inhibitor[J].Antimicrob Agents Chemother,2009,53(4):1377-1385.
    [54]PILOT-MATIAS T,TRIPATHI R,COHEN D,et al.In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450[J].Antimicrob Agents Chemother,2015,59(2):988-997.
    [55]TSAI CE,CHANG LW,CHANG YT,et al.A phase I/IIa study of safety,tolerability,and pharmacokinetic profiles of TG-2349,a pan-genotypic HCV protease inhibitor,in healthy East Asian and Caucasian subjects,and its antiviral activity in chronic hepatitis C patients[C].64th Annual Meeting of the American Association for the Study of Liver Disease.Washington DC,USA,2013:LB-18.
    [56]GAO M.Antiviral activity and resistance of HCV NS5A replication complex inhibitors[J].Curr Opin Virol,2013,3(5):514-520.
    [57]DEGOEY DA,RANDOLPH JT,LIU D,et al.Discovery of ABT-267,a pan-genotypic inhibitor of HCV NS5A[J].J Med Chem,2014,57(5):2047-2057.
    [58]KATI W,KOEV G,IRVIN M,et al.In vitro activity and resistance profile of dasabuvir,a nonnucleoside hepatitis C virus polymerase inhibitor[J].Antimicrob Agents Chemother,2015,59(3):1505-1511.
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