慢性乙型肝炎临床治愈(功能性治愈)专家共识

中华医学会感染病学分会，中华医学会肝病学分会

doi:10.3969/j.issn.1001-5256.2019.08.008

慢性乙型肝炎临床治愈(功能性治愈)专家共识

DOI: 10.3969/j.issn.1001-5256.2019.08.008

中华医学会感染病学分会，中华医学会肝病学分会

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中图分类号: R512.62
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出版历程
- 出版日期: 2019-08-20

The expert consensus on clinical cure (functional cure) of chronic hepatitis B

Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association

摘要

摘要:
慢性HBV感染仍是全球重大公共卫生问题。慢性乙型肝炎（慢乙肝）临床治愈（亦称功能性治愈）即完成有限疗程治疗后,血清HBsAg和HBV DNA持续检测不到、HBeAg阴转、伴或不伴HBsAg血清学转换,肝脏炎症缓解和组织病理学改善,终末期肝病发生率显著降低,是目前国内外最新慢乙肝防治指南推荐的理想治疗目标。临床实践证明,以直接抗病毒药物（DAA）[如核苷（酸）类似物（NA）]或免疫调节剂[如聚乙二醇化干扰素（PEG-IFN）α]序贯或联合治疗的优化方案针对部分优势人群显示出良好的疗效,开展了系列成功实现HBsAg阴转的多中心随机对照临床研究。《慢性乙型肝炎临床治愈（功能性治愈）专家共识》阐述了联合治疗方案的最新循证医学依据,并总结了慢乙肝临床治愈路线图,以指导临床医师治疗决策的制订。
- 乙型肝炎,慢性 /
- 乙型肝炎表面抗原 /
- 功能性治愈 /
- 临床治愈 /
- 共识
Abstract:
Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA) ]or immunomodulators [such as pegylated interferon alpha (PEG-IFN) ]for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
- hepatitis B, chronic /
- hepatitis B surface antigens /
- functional cure /
- clinical cure /
- consensus

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参考文献(99)

[1] SCHWEITZER A, HORN J, MIKOLAJCZYK RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection:A systematic review of data published between 1965 and2013[J]. Lancet, 2015, 386 (10003) :1546-1555.

[2] World Health Organization. Global hepatitis report 2017[R].Licence:CC BY-NC-SA 3. 0 IGO. 2017.

[3] SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B:A 2015update[J]. Hepatol Int, 2016, 10 (1) :1-98.

[4] TERRAULT NA, LOK A, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B:AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67 (4) :1560-1599.

[5] European Association for the Study of the Liver. EASL 2017clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67 (2) :370-398.

[6] HOU J, WANG G, WANG F, et al. Guideline of prevention and treatment for chronic hepatitis B (2015 Update) [J]. J Clin Transl Hepatol, 2017, 5 (4) :297-318.

[7] YUEN MF, WONG DK, FUNG J, et al. HBsAg seroclearance in chronic hepatitis B in Asian patients:Replicative level and risk of hepatocellular carcinoma[J]. Gastroenterology, 2008, 135 (4) :1192-1199.

[8] NING Q, WU D, WANG G, et al. Roadmap to functional cure of chronic hepatitis B:An expert consensus[J]. J Viral Hepat, 2019.[Epub ahead of print]

[9] TU T, BUDZINSKA MA, SHACKEL NA, et al. HBV DNA Integration:Molecular mechanisms and clinical implications[J].Viruses, 2017, 9 (4) :e75.

[10] VISVANATHAN K, SKINNER NA, THOMPSON AJ, et al. Regulation of toll-like receptor-2 expression in chronic hepatitis B by the precore protein[J]. Hepatology, 2007, 45 (1) :102-110.

[11] 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.

[12] 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.

[13] 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.

[14] 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.

[15] BERTOLETTI A, KENNEDY P. HBV antiviral immunity:Not all CD8 T cells are born equal[J]. Gut, 2019, 68 (5) :770-773.

[16] SALIMZADEH L, LE BERT N, DUTERTRE CA, et al. PD-1blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection[J]. J Clin Invest, 2018, 128 (10) :4573-4587.

[17] TANG L, COVERT E, WILSON E, et al. Chronic hepatitis B infection:A review[J]. JAMA, 2018, 319 (17) :1802-1813.

[18] LEVRERO M, SUBIC M, VILLERET F, et al. Perspectives and limitations for nucleo (t) side analogs in future HBV therapies[J]. Curr Opin Virol, 2018, 30:80-89.

[19] DOLMAN GE, KOFFAS A, MASON WS, et al. Why, who and when to start treatment for chronic hepatitis B infection[J].Curr Opin Virol, 2018, 30:39-47.

[20] LIU F, WANG XW, CHEN L, et al. Systematic review with meta-analysis:Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance[J]. Aliment Pharmacol Ther, 2016, 43 (12) :1253-1261.

[21] KONG Y, YOU H, JIA J. Oral antiviral therapy reduces the risk of hepatocellular carcinoma in persons with chronic hepatitis B infection:Combining evidence and common sense[J]. Hepatol Int, 2016, 10 (2) :239-241.

[22] LEVRERO M, POLLICINO T, PETERSEN J, et al. Control of cccDNA function in hepatitis B virus infection[J]. J Hepatol, 2009, 51 (3) :581-592.

[23] SUNG JJ, WONG ML, BOWDEN S, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy[J]. Gastroenterology, 2005, 128 (7) :1890-1897.

[24] WERLE-LAPOSTOLLE B, BOWDEN S, LOCARNINI S, et al.Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy[J].Gastroenterology, 2004, 126 (7) :1750-1758.

[25] LAI CL, WONG D, IP P, et al. Reduction of covalently closed circular DNA with long-term nucleos (t) ide analogue treatment in chronic hepatitis B[J]. J Hepatol, 2017, 66 (2) :275-281.

[26] SADLER AJ, WILLIAMS BR. Interferon-inducible antiviral effectors[J]. Nat Rev Immunol, 2008, 8 (7) :559-568.

[27] 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.

[28] 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 cccDNA minichromosome[J]. J Clin Invest, 2012, 122 (2) :529-537.

[29] BUSTER EH, HANSEN BE, LAU GK, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa[J]. Gastroenterology, 2009, 137 (6) :2002-2009.

[30] 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.

[31] WU D, NING Q. Toward a cure for hepatitis B virus infection:Combination therapy involving viral suppression and immune modulation and long-term outcome[J]. J Infect Dis, 2017, 216 (Suppl 8) :s771-s777.

[32] TESTONI B, LEVRERO M, ZOULIM F. Challenges to a cure for HBV infection[J]. Semin Liver Dis, 2017, 37 (3) :231-242.

[33] NASSAL M. HBV cccDNA:Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B[J]. Gut, 2015, 64 (12) :1972-1984.

[34] 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.

[35] MICCO L, PEPPA D, LOGGI E, et al. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B[J]. J Hepatol, 2013, 58 (2) :225-233.

[36] 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.

[37] CHEN T, ZHU L, SHI A, et al. Functional restoration of CD56bright NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B[J]. Hepatol Int, 2017, 11 (5) :419-428.

[38] 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.

[39] GILL US, KENNEDY P. The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B:Considerations for future novel therapeutics[J]. J Viral Hepat, 2019, 26 (1) :4-15.

[40] 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.

[41] 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.

[42] 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.

[43] 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.

[44] SHI A, ZHANG X, XIAO F, et al. CD56brightnatural killer cells induce HBsAg reduction via cytolysis and cccDNA decay in long-term entecavir-treated patients switching to peginterferon alfa-2a[J]. J Viral Hepat, 2018, 25 (11) :1352-1362.

[45] LAU GK, PIRATVISUTH T, LUO KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBe Ag-positive chronic hepatitis B[J]. N Engl J Med, 2005, 352 (26) :2682-2695.

[46] 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.

[47] 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.

[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] 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.

[50] 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.

[51] AHN SH, MARCELLIN P, MA X, et al. Hepatitis B surface antigen loss with tenofovir disoproxil fumarate plus peginterferon alfa-2a:Week 120 analysis[J]. Dig Dis Sci, 2018, 63 (12) :3487-3497.

[52] HAGIWARA S, NISHIDA N, WATANABE T, et al. Sustained antiviral effects and clearance of hepatitis surface antigen after combination therapy with entecavir and pegylated interferon in chronic hepatitis B[J]. Antivir Ther, 2018, 23 (6) :513-521.

[53] SERFATY L, THABUT D, ZOULIM F, et al. Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone:Results of a pilot study[J]. Hepatology, 2001, 34 (3) :573-577.

[54] NING Q, HAN M, SUN Y, et al. Switching from entecavir to PegIFN 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.

[55] 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.

[56] BOGLIONE L, D'AVOLIO A, CARITI G, et al. Sequential therapy with entecavir and PEG-INF 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.

[57] TAMAKI N, KUROSAKI M, KUSAKABE A, et al. Hepatitis B surface antigen reduction by switching from long-term nucleoside/nucleotide analogue administration to pegylated interferon[J]. J Viral Hepat, 2017, 24 (8) :672-678.

[58] XIE Q, ZHOU H, BAI X, et al. A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B"e"antigenpositive chronic hepatitis B[J]. Clin Infect Dis, 2014, 59 (12) :1714-1723.

[59] HU P, SHANG J, ZHANG W, et al. HBsAg loss with Peg-interferon alfa-2a in hepatitis B patients with partial response to nucleos (t) ide analog:New switch study[J]. J Clin Transl Hepatol, 2018, 6 (1) :25-34.

[60] CHAN H, CHAN F, HUI AJ, et al. Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir-A prospective study[J]. J Viral Hepat, 2019, 26 (1) :126-135.

[61] WU D, WANG P, HAN M, et al. Sequential combination therapy with interferon, interleukin-2 and therapeutic vaccine in entecavir-suppressed chronic hepatitis B patients:The Endeavor study[J]. Hepatol Int, 2019.

[62] KITTNER JM, SPRINZL MF, GRAMBIHLER A, et al. Adding pegylated interferon to a current nucleos (t) ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B[J]. J Clin Virol, 2012, 54 (1) :93-95.

[63] OUZAN D, PNARANDA G, JOLY H, et al. Add-on peg-interferon leads to loss of HBs Ag in patients with HBe Ag-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs[J]. J Clin Virol, 2013, 58 (4) :713-717.

[64] CHI H, HANSEN BE, GUO S, et al. Pegylated interferon alfa-2b add-on treatment in hepatitis B virus envelope antigen-positive chronic hepatitis B patients treated with nucleos (t) ide analogue:A randomized, controlled trial (PEGON) [J]. J Infect Dis, 2017, 215 (7) :1085-1093.

[65] LI GJ, YU YQ, CHEN SL, et al. Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBe Ag) seroconversion in HBe Ag-positive chronic hepatitis B patients receiving longterm entecavir treatment[J]. Antimicrob Agents Chemother, 2015, 59 (7) :4121-4128.

[66] DEGASPERI E, GALMOZZI E, FACCHETTI F, et al. TLL1 variants do not predict hepatocellular carcinoma development in HCV cirrhotic patients treated with direct-acting antivirals[J].J Viral Hepat, 2019.[Epub ahead of print]

[67] BOURLIRE M, RABIEGA P, GANNE-CARRIE N, et al.Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos (t) ide analogue therapy versus nucleos (t) ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA:A randomised, controlled, open-label trial[J]. Lancet Gastroenterol Hepatol, 2017, 2 (3) :177-188.

[68] 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.

[69] JINDAL A, VYAS AK, KUMAR D, et al. Higher efficacy of pegylated interferon-α2b add-on therapy in hepatitis B envelope antigen-positive chronic hepatitis B patients on tenofovir monotherapy[J]. Hepatol Res, 2018, 48 (6) :451-458.

[70] CANNIZZO ES, TINCATI C, BINDA F, et al. Unconventional T cells in chronic hepatitis B patients on long-term suppressive therapy with tenofovir followed by a Peg-IFN add-on strategy:A randomized study[J]. J Viral Hepat, 2018, 25 (4) :381-390.

[71] QIU K, LIU B, LI SY, et al. Systematic review with meta-analysis:Combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance[J]. Aliment Pharmacol Ther, 2018, 47 (10) :1340-1348.

[72] YAN L, ZHU C, LI J, et al. Entecavir add-on or switch-to pegylated interferon improves HBsAg clearance in HBe antigen negative chronic hepatitis B patients[J]. Infect Drug Resist, 2018, 11:2001-2009.

[73] TATSUKAWA Y, TSUGE M, KAWAKAMI Y, et al. Reduction of hepatitis B surface antigen in sequential versus add-on pegylated interferon to nucleoside/nucleotide analogue therapy in HBe-antigen-negative chronic hepatitis B patients:A pilot study[J]. Antivir Ther, 2018, 23 (8) :639-646.

[74] LIM SG. HCV management in resource-constrained countries[J]. Hepatol Int, 2017, 11 (3) :245-254.

[75] HONER ZU SIEDERDISSEN C, CORNBERG M. The role of HBsAg levels in the current management of chronic HBV infection[J]. Ann Gastroenterol, 2014, 27 (2) :105-112.

[76] MARTINOT-PEIGNOUX M, LAPALUS M, ASSELAH T, et al.HBsAg quantification:Useful for monitoring natural history and treatment outcome[J]. Liver Int, 2014, 34 (Suppl 1) :97-107.

[77] 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 (1) :240-241.

[78] HUANG J, ZHANG K, CHEN W, et al. Switching to PegIFNα-2b leads to HBsAg loss in patients with low HBs Ag levels and HBV DNA suppressed by NAs[J]. Sci Rep, 2017, 7 (1) :13383.

[79] HAN MF, WU D, TAN DM, et al. Combination/sequential therapy with ETV, Peg-IFN alpha-2b and GMCSF enhanced HBsAg loss and appearance of HBsAb in NA suppressed CHB patients (the Anchor A study) :An interim analysis[J]. Hepatology, 2017:o29.

[80] GAO Z, ZHU X, LIN B, et al. The optimizing treatment of peg interferon alfa in hbeag negative chronic hepatitis B patients with low level HBsAg:A multicenter real world study (Interferon Cure Study, I CURE Study) [J]. Hepatology, 2018, 68:246A.

[81] XIE Q, CAI W, OUYANG LJ, et al. Effectiveness of response-guided peginterferon alfa-2a therapy in nucleos (t) ide analogues treated patients with HBe Ag-positive chronic hepatitis B:Interim analysis of a prospective, multicenter, randomized study[J]. Hepatology 2018, 68:232A.

[82] SU TH, HSU CS, CHEN CL, et al. Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B[J]. Antivir Ther, 2010, 15 (8) :1133-1139.

[83] TSENG TC, KAO JH. Clinical utility of quantitative HBs Ag in natural history and nucleos (t) ide analogue treatment of chronic hepatitis B:New trick of old dog[J]. J Gastroenterol, 2013, 48 (1) :13-21.

[84] CAO Z, LIU Y, MA L, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66 (4) :1058-1066.

[85] SUN J, MA H, XIE Q, et al. Response-guided peginterferon therapy in patients with HBe Ag-positive chronic hepatitis B:A randomized controlled study[J]. J Hepatol, 2016, 65 (4) :674-682.

[86] WANG CC, TSENG KC, HSIEH TY, et al. Assessing the durability of entecavir-treated hepatitis B using quantitative HBsAg[J]. Am J Gastroenterol, 2016, 111 (9) :1286-1294.

[87] FUNG J, CHEUNG KS, WONG DK, et al. Long-term outcomes and predictive scores for hepatocellular carcinoma and hepatitis B surface antigen seroclearance after hepatitis B eantigen seroclearance[J]. Hepatology, 2018, 68 (2) :462-472.

[88] HOU FQ, SONG LW, YUAN Q, et al. Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBe Ag-positive chronic hepatitis B patients receiving peginterferon[J]. Theranostics, 2015, 5 (3) :218-226.

[89] FAN R, SUN J, YUAN Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBe Ag seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos (t) ide analogues[J]. Gut, 2016, 65 (2) :313-320.

[90] XU JH, SONG LW, LI N, et al. Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir[J]. J Viral Hepat, 2017, 24 (2) :148-154.

[91] HSU YC, TSENG CH, KAO JH. Quantification of hepatitis B core antibody helps predict clinical relapse after cessation of nucleos (t) ide analogues in chronic hepatitis B Patients:More needs to be done[J]. Clin Gastroenterol Hepatol, 2019, 17 (5) :1000-1001.

[92] HU HH, LIU J, CHANG CL, et al. Level of hepatitis B (HB) Core antibody associates with seroclearance of HBV DNA and HB surface antigen in HB e antigen-seronegative patients[J]. Clin Gastroenterol Hepatol, 2019, 17 (1) :172-181. e1.

[93] TANAKA E, MATSUMOTO A. Guidelines for avoiding risks resulting from discontinuation of nucleoside/nucleotide analogs in patients with chronic hepatitis B[J]. Hepatol Res, 2014, 44 (1) :1-8.

[94] WANG J, SHEN T, HUANG X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound[J]. J Hepatol, 2016, 65 (4) :700-710.

[95] van BMMEL F, BARTENS A, MYSICKOVA A, et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors[J]. Hepatology, 2015, 61 (1) :66-76.

[96] WANG J, CHEN X, WU Y, et al. Serum HBV RNA is a potential predictor of hepatitis B surface antigen reversion[J]. Hepatol Commun, 2018, 2 (10) :1168-1171.

[97] WU Y, LIU Y, LU J, et al. Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance[J]. Clin Gastroenterol Hepatol, 2019.[Epub ahead of print]

[98] YIP TC, WONG GL, CHAN HL, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos (t) ide analogues[J]. J Hepatol, 2019, 70 (3) :361-370.

[99] KOFFAS A, DOLMAN GE, KENNEDY PT. Hepatitis B virus reactivation in patients treated with immunosuppressive drugs:A practical guide for clinicians[J]. Clin Med (Lond) , 2018, 18 (3) :212-218.

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