[1]OTT JJ, STEVENS GA, GROEGER J, et al.Global epidemiology of hepatitis B virus infection:new estimates of age-specific HBs Ag seroprevalence and endemicity[J].Vaccine, 2012, 30 (12) :2212
|
[2]WHO.Hepatitis B factsheet[EB/OL].http://www.who.int/mediacentre/factsheets/fs204/en/.
|
[3]LEVRERO M, POLLICINO T, PETERSEN J, et al.Control of ccc DNA function in hepatitis B virus infection[J].J Hepatol, 2009, 51 (3) :581-592.
|
[4]OP den BROUW ML, BINDA RS, van ROOSMALEN MH, et al.Hepatitis B virus surface antigen impairs myeloid dendritic cell function:a possible immune escape mechanism of hepatitis B virus[J].Immunology, 2009, 126 (2) :280-289.
|
[5]LANG T, LO C, SKINNER N, et al.The hepatitis B e antigen (HBe Ag) targets and suppresses activation of the toll-like receptor signaling pathway[J].J Hepatol, 2011, 55 (4) :762-769.
|
[6]DAS A, HOARE M, DAVIES N, et al.Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection[J].J Exp Med, 2008, 205 (9) :2111-2124.
|
[7]BONI C, FISICARO P, VALDATTA C, et al.Characterization of hepatitis B virus (HBV) -specific T-cell dysfunction in chronic HBV infection[J].J Virol, 2007, 81 (8) :4215-4225.
|
[8] European Association for the Study of the Liver.EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J].J Hepatol, 2017, 67 (2) :370-398.
|
[9]LAMPERTICO P, LIAW YF.New perspectives in the therapy of chronic hepatitis B[J].Gut, 2012, 61 (Suppl 1) :i18-i24.
|
[10]SCAGLIONE SJ, LOK AS.Effectiveness of hepatitis B treatment in clinical practice[J].Gastroenterology, 2012, 142 (6) :1360-1368.e1.
|
[11]CHAN HL, WONG VW, TSE AM, et al.Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response[J].Clin Gastroenterol Hepatol, 2007, 5 (12) :1462-1468.
|
[12]MOUCARI R, MACKIEWICZ V, LADA O, et al.Early serum HBs Ag drop:a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBe Ag-negative patients[J].Hepatology, 2009, 49 (4) :1151-1157.
|
[13]MARTINOT-PEIGNOUX M, LAPALUS M, ASSELAH T, et al.HBs Ag quantification:useful for monitoring natural history and treatment outcome[J].Liver Int, 2014, 34 (Suppl 1) :97-107.
|
[14]ARENDS P, SONNEVELD MJ, ZOUTENDIJK R, et al.Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B:limited role for risk scores in Caucasians[J].Gut, 2015, 64 (8) :1289-1295.
|
[15]DARGAN A, WONG SY, COBEN R, et al.Persistent risk for hepatocellular carcinoma after more than a decade of successful hepatitis B virus suppression[J].Minerva Gastroenterol Dietol, 2017, 63 (1) :74-76.
|
[16] SARIN SK, KUMAR M, LAU GK, et al.Asian-Pacific clinical practice guidelines on the management of hepatitis B:a 2015 update[J].Hepatol Int, 2016, 10 (1) :1-98.
|
[17]TERRAULT NA, BZOWEJ NH, CHANG KM, et al.AASLD guidelines for treatment of chronic hepatitis B[J].Hepatology, 2016, 63 (1) :261-283.
|
[18]SADLER AJ, WILLIAMS BR.Interferon-inducible antiviral effectors[J].Nat Rev Immunol, 2008, 8 (7) :559-568.
|
[19]SAMUEL CE.Antiviral actions of interferons[J].Clin Microbiol Rev, 2001, 14 (4) :778-809.
|
[20]BONI C, LACCABUE D, LAMPERTICO P, et al.Restored function of HBV-specific T cells after long-term effective therapy with nucleos (t) ide analogues[J].Gastroenterology, 2012, 143 (4) :963-973.e9.
|
[21]DANDRI M, LOCARNINI S.New insight in the pathobiology of hepatitis B virus infection[J].Gut, 2012, 61 (Suppl 1) :16-17.
|
[22]WIELAND SF, EUSTAQUIO A, WHITTEN-BAUER C, et al.Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids[J].Proc Natl Acad Sci U S A, 2005, 102 (28) :9913-9917.
|
[23]XU C, GUO H, PAN XB, et al.Interferons accelerate decay of replication-competent nucleocapsids of hepatitis B virus[J].J Virol, 2010, 84 (18) :9332-9340.
|
[24]BELLONI L, ALLWEISS L, GUERRIERI F, et al.IFN-αinhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear ccc DNA minichromosome[J].J Clin Invest, 2012, 122 (2) :529-537.
|
[25]BRUNETTO MR, BONINO F.Interferon therapy of chronic hepatitis B[J].Intervirology, 2014, 57 (3-4) :163-170.
|
[26]KIM SR, YANG J, KUDO M, et al.Recent advances in the management of chronic hepatitis B[J].Hepat Mon, 2011, 11 (8) :601-611.
|
[27]LAU GK, PIRATVISUTH T, LUO KX, et al.Peginterferon alfa-2a HBe Ag-positive chronic hepatitis B study group.Peginterferon alfa-2a, lamivudine, and the combination for HBe Ag-positive chronic hepatitis B[J].N Engl J Med, 2005, 352 (26) :2682-2695.
|
[28]JANSSEN HL, van ZONNEVELD M, SENTURK H, et al.Pegylated interferon alfa-2b alone or in combination with lamivudine for HBe Ag-positive chronic hepatitis B:a randomised trial[J].Lancet, 2005, 365 (9454) :123-129.
|
[29]CHANG TT, GISH RG, de MAN R, et al.A comparison of entecavir and lamivudine for HBe Ag-positive chronic hepatitis B[J].N Engl J Med, 2006, 354 (10) :1001-1010.
|
[30]LAI CL, CHIEN RN, LEUNG NW, et al.A one-year trial of lamivudine for chronic hepatitis B[J].N Engl J Med, 1998, 339 (12) :61-68.
|
[31]LAI CL, GANE E, LIAW YF, et al.Telbivudine versus lamivudine in patients with chronic hepatitis B[J].N Engl J Med, 2007, 357 (25) :2576-2588.
|
[32]MARCELLIN P, CHANG TT, LIM SG, et al.Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B[J].N Engl J Med, 2003, 348 (9) :808-816.
|
[33]MARCELLIN P, HEATHCOTE EJ, BUTI M, et al.Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B[J].N Engl J Med, 2008, 359 (23) :2442-2455.
|
[34]LIAW YF, GANE E, LEUNG N, et al.2-Year GLOBE trial results:telbivudine is superior to lamivudine in patients with chronic hepatitis B[J].Gastroenterology, 2009, 136 (2) :486-495.
|
[35]CHANG TT, LAI CL, KEW YOON S, et al.Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B[J].Hepatology, 2010, 51 (2) :422-430.
|
[36]GISH RG, LOK AS, CHANG TT, et al.Entecavir therapy for up to96 weeks in patients with HBe Ag-positive chronic hepatitis B[J].Gastroenterology, 2007, 133 (5) :1437-1444.
|
[37]MARCELLIN PGE, FLISIAK R, TRINH H, et al.Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic response with no detectable resistance:8 year results from two phase 3 trials[J].Hepatology, 2014, 60 (10) :313-314.
|
[38]MARCELLIN P, LAU GK, BONINO F, et al.Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBe Ag-negative chronic hepatitis B[J].N Engl J Med, 2004, 351 (12) :1206-1217.
|
[39]TASSOPOULOS NC, VOLPES R, PASTORE G, et al.Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B[J].Hepatology, 1999, 29 (3) :889-896.
|
[40]LAI CL, SHOUVAL D, LOK AS, et al.Entecavir versus lamivudine for patients with HBe Ag-negative chronic hepatitis B[J].N Engl J Med, 2006, 354 (10) :1011-1020.
|
[41]HADZIYANNIS SJ, TASSOPOULOS NC, HEATHCOTE EJ, et al.Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B[J].N Engl J Med, 2003, 348 (12) :800-807.
|
[42]HADZIYANNIS SJ, TASSOPOULOS NC, HEATHCOTE EJ, et al.Long-term therapy with adefovir dipivoxil for HBe Ag-negative chronic hepatitis B for up to 5 years[J].Gastroenterology, 2006, 131 (6) :1743-1751.
|
[43] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.
|
[44]THIMME R, DANDRI M.Dissecting the divergent effects of interferon-alpha on immune cells:time to rethink combination therapy in chronic hepatitis B?[J].J Hepatol, 2013, 58 (2) :205-209.
|
[45]WU D, HAN M, NING Q.An integration of deep viral suppression with sequential immune modulation (cocktail therapy) to restore antiviral capacity:the future of chronic hepatitis B?[J].J Hepatol, 2015, 62 (2) :240-241.
|
[46]PICCOLO P, LENCI I, DEMELIA L, et al.A randomized controlled trial of pegylated interferon-alpha2a plus adefovir dipivoxil for hepatitis B e antigen-negative chronic hepatitis B[J].Antivir Ther, 2009, 14 (8) :1165-1174.
|
[47]WURSTHORN K, LUTGEHETMANN M, DANDRI M, et al.Peginterferon alpha-2b plus adefovir induce strong ccc DNA decline and HBs Ag reduction in patients with chronic hepatitis B[J].Hepatology, 2006, 44 (3) :675-684.
|
[48]MARCELLIN P, WURSTHORN K, WEDEMEYER H, et al.Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy[J].J Hepatol, 2015, 62 (1) :41-47.
|
[49]MARCELLIN P, AHN SH, MA X, et al.Combination of tenofovir disoproxil fumarate and peginterferonα-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B[J].Gastroenterology, 2016, 150 (1) :134-144.e10.
|
[50]JANSEN L, de NIET A, STELMA F, et al.HBs Ag loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels[J].J Hepatol, 2014, 61 (4) :730-737.
|
[51]STELMA F, JANSEN L, SINNIGE MJ, et al.HLA-C and KIR combined genotype as new response marker for HBe Ag-positive chronic hepatitis B patients treated with interferon-based combination therapy[J].J Viral Hepat, 2016, 23 (8) :652-659.
|
[52]TANGKIJVANICH P, CHITTMITTRAPRAP S, POOVORAWAN K, et al.A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBe Ag-negative chronic hepatitis B:role of host and viral factors associated with treatment response[J].J Viral Hepat, 2016, 23 (6) :427-438.
|
[53]NING Q, HAN M, SUN Y, et al.Switching from entecavir to Peg IFN alfa-2a in patients with HBe Ag-positive chronic hepatitis B:a randomised open-label trial (OSST trial) [J].J Hepatol, 2014, 61 (4) :777-784.
|
[54]HAN M, JIANG J, HOU J, et al.Sustained immune control in HBe Ag-positive patients who switched from entecavir therapy to pegylated interferon-α2a:1 year follow-up of the OSST study[J].Antivir Ther, 2016, 21 (4) :337-344.
|
[55]BOGLIONE L, D'AVOLIO A, CARITI G, et al.Sequential therapy with entecavir and PEGINF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes[J].J Viral Hepat, 2013, 20 (4) :e11-e19.
|
[56]HU P, GONG G, XIE Q, et al.High HBs Ag loss rate in HBe Ag loss CHB patients SWITCH from NUC to Peg-IFN alfa-2 a (NEW SWITCH study) [C].Asian Pacific Association for the Study of the Liver, 2017:s46.
|
[57]WU D, HAN MF, CHEN YP, et al.THU-165-Sequential combination therapy with IFN, rh IL-2 and therapeutic vaccine enhanced HBs Ag loss in entecavir-suppressed CHB patients (the Endeavor study) :an interim analysis[J].J Hepatol, 2017, 66 (1) :s261.
|
[58]BROUWER WP, XIE Q, SONNEVELD MJ, et al.Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B:a multicenter randomized trial (ARES study) [J].Hepatology, 2015, 61 (5) :1512-1522.
|
[59]HNER ZU SIEDERDISSEN C, CORNBERG M.The role of HBs Ag levels in the current management of chronic HBV infection[J].Ann Gastroenterol, 2014, 27 (2) :105-112.
|
[60]HAN MF, WU D, TAN DM, et al.Combination/sequential therapy with ETV, Peg-IFN alpha-2b and GMCSF enhanced HBs Ag loss and appearance of HBs Ab in NA suppressed CHB patients (the Anchor A study) :an interim analysis[C].American Association for the Study of Liver Diseases, 2017:o29.
|
[61]MAINI MK, SCHURICH A.The molecular basis of the failed immune response in chronic HBV:therapeutic implications[J].J Hepatol, 2010, 52 (4) :616-619.
|
[62]THIMME R, WIELAND S, STEIGER C, et al.CD8 (+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection[J].J Virol, 2003, 77 (1) :68-76.
|
[63]BILLERBECK E, BOTTLER T, THIMME R.Regulatory T cells in viral hepatitis[J].World J Gastroenterol, 2007, 13 (36) :4858-4864.
|
[64]MICCO L, PEPPA D, LOGGI E, et al.Differential boosting of innate and adaptive antiviral responses during pegylated-interferonalpha therapy of chronic hepatitis B[J].J Hepatol, 2013, 58 (2) :225-233.
|
[65]PENNA A, LACCABUE D, LIBRI I, et al.Peginterferon-αdoes not improve early peripheral blood HBV-specific T-cell responses in HBe Ag-negative chronic hepatitis[J].J Hepatol, 2012, 56 (6) :1239-1246.
|
[66]PEPPA D, MICCO L, JAVAID A, et al.Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection[J].PLo S Pathog, 2010, 6 (12) :e1001227.
|
[67]ALLWEISS L, LTGEHETMANN M, VOLZ T, et al.Pegylatedinterferon-alpha alone or in combination with entecavir restores ISG responsiveness and reduces intrahepatic viral loads and antigenemia in hepatitis B virus infected humanized mice[J].J Hepatol, 2012, 56 (Suppl 2) :s18-s19.
|
[68]de NIET A, STELMA F, JANSEN L, et al.Restoration of T cell function in chronic hepatitis B patients upon treatment with interferon based combination therapy[J].J Hepatol, 2016, 64 (3) :539-546.
|
[69]TAN AT, HOANG LT, CHIN D, et al.Reduction of HBV replication prolongs the early immunological response to IFNαtherapy[J].J Hepatol, 2014, 60 (1) :54-61.
|
[70]YAN W, WU D, WANG X, et al.Upregulation of NKG2C+natural killer cells, TLR-2 expression on monocytes and downregulation of regulatory T-cells influence PEG-IFN treatment efficacy in entecavir-suppressed patients with CHB[J].Antivir Ther, 2015, 20 (6) :591-602.
|
[71]HAN M, LI Y, WU W, et al.Altered expression of interferonstimulated genes is strongly associated with therapeutic outcomes in hepatitis B virus infection[J].Antiviral Res, 2017, 147:75-85.
|
[72]LUCIFORA J, XIA Y, REISINGER F, et al.Specific and nonhepatotoxic degradation of nuclear hepatitis B virus ccc DNA[J].Science, 2014, 343 (6189) :1221-1228.
|
[73]LI Y, XIA Y, HAN M, et al.IFN-α-mediated base excision repair pathway correlates with antiviral response against hepatitis B virus infection[J].Sci Rep, 2017, 7 (1) :12715.
|
[74]LIN CL, KAO JH.Review article:novel therapies for hepatitis B virus cure-advances and perspectives[J].Aliment Pharmacol Ther, 2016, 44 (3) :213-222.
|
[75]YANG HC, KAO JH.Viral hepatitis.HBV cure-can we pin our hopes on immunotherapy?[J].Nat Rev Gastroenterol Hepatol, 2015, 12 (3) :129-131.
|