How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?
Tóm tắt
Từ khóa
Tài liệu tham khảo
Schweitzer, 2015, Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013, Lancet, 386, 1546, 10.1016/S0140-6736(15)61412-X
2018, Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study, Lancet Gastroenterol Hepatol, 3, 383, 10.1016/S2468-1253(18)30056-6
World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. Website: https://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/. Accessed on 20 April 2021.
Cornberg, 2019, Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference, J Hepatol
Yip, 2019, HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues, J Hepatol, 70, 361, 10.1016/j.jhep.2018.10.014
Kim, 2014, HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability, Gut, 63, 1325, 10.1136/gutjnl-2013-305517
Kim, 2020, Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study, Gut, 69, 2214, 10.1136/gutjnl-2019-320015
Martinez, 2021, Covalently closed circular DNA: the ultimate therapeutic target for curing HBV infections, J Hepatol, 75, 706, 10.1016/j.jhep.2021.05.013
Evens, 2011, Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports, Ann Oncol, 22, 1170, 10.1093/annonc/mdq583
Caviglia, 2018, Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: a new tool to detect occult infection, J Hepatol, 69, 301, 10.1016/j.jhep.2018.03.021
Murai, 2020, Novel anti-HBV therapies using CRISPR/cas9 targeting HBV genome strongly suppress HBV, Hepatology, 72, 61A
Boyd, 2016, Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients, J Hepatol, 65, 683, 10.1016/j.jhep.2016.05.014
Huang, 2021, Rapid turnover of hepatitis B virus covalently closed circular DNA indicated by monitoring emergence and reversion of signature-mutation in treated chronic hepatitis B patients, Hepatology, 73, 41, 10.1002/hep.31240
Chow, 2020, Long term nucleos(t)ide analogue therapy reduced the extent of HBV DNA integration in chronic hepatitis B patients, Hepatology, 72, 19A
Hsu, 2020, Tenofovir disoproxil fumarate treatment reduces the number of transcriptionally active viral integrations in chronically infected HBV patients, Hepatology, 17, 13A
Soulette, 2021, VALIANT: a targeted long-read approach to study translocation and mRNA isoforms associated with HBV integration, J Hepatol, 75, S284
Wooddell, 2017, RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg, Sci Transl Med, 9, 10.1126/scitranslmed.aan0241
Cornberg, 2018, Hepatitis: No cure for hepatitis B and D without targeting integrated viral DNA?, Nat Rev Gastroenterol Hepatol, 15, 195, 10.1038/nrgastro.2017.185
Schuch, 2019, Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load, Gut, 68, 905, 10.1136/gutjnl-2018-316641
Honer Zu Siederdissen, 2014, The role of HBsAg levels in the current management of chronic HBV infection, Ann Gastroenterol, 27, 105
Lebosse, 2017, Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B, J Hepatol, 66, 897, 10.1016/j.jhep.2016.12.024
Martinet, 2012, Altered functions of plasmacytoid dendritic cells and reduced cytolytic activity of natural killer cells in patients with chronic HBV infection, Gastroenterology, 143, 1586, 10.1053/j.gastro.2012.08.046
Ren, 2019, Effects of pegylated interferon-alpha based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B, J Viral Hepat, 26, 5, 10.1111/jvh.13150
Jeng, 2021, Should treatment indications for chronic hepatitis B Be expanded?, Clin Gastroenterol Hepatol, 19, 2006, 10.1016/j.cgh.2020.04.091
Yip, 2018, Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients, J Hepatol, 68, 63, 10.1016/j.jhep.2017.09.018
Cornberg, 2017, The role of quantitative hepatitis B surface antigen revisited, J Hepatol, 66, 398, 10.1016/j.jhep.2016.08.009
Hadziyannis, 2012, Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir, Gastroenterology, 143, 629, 10.1053/j.gastro.2012.05.039
Chen, 2018, Long-term incidence and predictors of hepatitis B surface antigen loss after discontinuing nucleoside analogues in noncirrhotic chronic hepatitis B patients, Clin Microbiol Infect, 24, 997, 10.1016/j.cmi.2017.12.013
Jeng, 2018, Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B, Hepatology, 68, 425, 10.1002/hep.29640
Wong, 2020, The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg-negative chronic hepatitis B, Liver Int, 40, 549, 10.1111/liv.14330
Berg, 2017, Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study, J Hepatol, 67, 918, 10.1016/j.jhep.2017.07.012
Liem, 2019, Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study), Gut, 68, 2206, 10.1136/gutjnl-2019-318981
van Bommel, 2021, Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients: results of the Stop-NUC trial (LBO06), J Hepatol, 73, S118, 10.1016/S0168-8278(20)30755-8
Hirode, 2020, HBsAg loss is higher among Caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multiethnic cohort of patients with chronic hepatitis b (RETRECT-B study), Hepatology, 72, 19A
Kao, 2021, APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients, Hepatol Int, 15, 833, 10.1007/s12072-021-10223-5
Hadziyannis, 2020, Current practice and contrasting views on discontinuation of nucleos(t)ide analog therapy in chronic hepatitis B, Expert Rev Gastroenterol Hepatol, 14, 243, 10.1080/17474124.2020.1738219
Lucifora, 2014, Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA, Science, 343, 1221, 10.1126/science.1243462
Nishio, 2021, Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection, Sci Transl Med, 13, 10.1126/scitranslmed.aba6322
Marcellin, 2016, Combination of tenofovir disoproxil fumarate and peginterferon alpha-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B, Gastroenterology, 150, 134, 10.1053/j.gastro.2015.09.043
Liu, 2020, Effect of combination treatment based on interferon and nucleos(t)ide analogues on functional cure of chronic hepatitis B: a systematic review and meta-analysis, Hepatol Int, 14, 958, 10.1007/s12072-020-10099-x
Lok, 2021, Endpoints and new options for treatment of chronic hepatitis D, Hepatology, 10.1002/hep.32082
Yuen, 2019, Antiviral activity, safety, and pharmacokinetics of capsid assembly modulator NVR 3-778 in patients with chronic HBV infection, Gastroenterology, 156, 1392, 10.1053/j.gastro.2018.12.023
Janssen, 2020, Efficacy and safety results of the phase 2 JNJ-56136379 JADE study in patients with chronic hepatitis B: interim week 24 data, J Hepatol, 73, S219, 10.1016/S0168-8278(20)30773-X
Zoulim, 2020, JNJ-56136379, an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection, Gastroenterology, 159, 521, 10.1053/j.gastro.2020.04.036
Yuen, 2020, Safety, pharmacokinetics, and antiviral effects of ABI-H0731, a hepatitis B virus core inhibitor: a randomised, placebo-controlled phase 1 trial, Lancet Gastroenterol Hepatol, 5, 152, 10.1016/S2468-1253(19)30346-2
Yuen, 2021, Safety, pharmacokinetics, and antiviral activity of RO7049389, a core protein allosteric modulator, in patients with chronic hepatitis B virus infection: a multicentre, randomised, placebo-controlled, phase 1 trial, Lancet Gastroenterol Hepatol, 6, 723, 10.1016/S2468-1253(21)00176-X
Yuen, 2020, Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-positive chronic hepatitis B infection in a long-term extension study, J Hepatol, 73, S140, 10.1016/S0168-8278(20)30790-X
Gane, 2021, Virologic response and safety following discontinuation of treatment with the core inhibitor vebicorvir and a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg positive or negative chronic hepatitis B virus infection, J Hepatol, 75, S736
Mani, 2021, Preclinical antiviral profile of AB-836, a potent, highly selective hepatitis B virus capsid inhibitor, J Hepatol, 75, S281
Dawei Cai, 2021, Second generation Hepatitis B Virus core inhibitors ABI-H2158 and ABI-H3733 have enhanced potency and target coverage for both antiviral inhibition and covalently closed circular DNA establishment activities, J Hepatol, 75, S299
2021
Verbinnen, 2020, Viral sequence analysis of chronic hepatitis B (CHB) patients treated with the capsid assembly modulator (CAM-N) JNJ-56136379 (JNJ-6379) as monotherapy in the JADE phase 2a study, Hepatology, 72, 521A
Yuen, 2020, HBV RNAI inhibitor RG6346 in phase 1b-2a trial was safe, well tolerated, and resulted in substantial and durable reductions in serum HBsAg levels, Hepatology, 72, LP32
Gane, 2020, Preliminary safety and antiviral activity of VIR-2218, an X-targeting RNAi therapeutic, in chronic hepatitis B patients, J Hepatol, 73, S50, 10.1016/S0168-8278(20)30647-4
Yuen, 2020, Safety and pharmacodynamics of the gal-Nac siRNA AB-729 in subjects with chronic hepatitis B infection, Hepatology, 72, 62A
Gane, 2019, Dose response with the RNA interference therapy JNJ-3989 combined with nucleos(t)ide analogue treatment in expanded cohorts of patients with chronic hepatitis B, Hepatology, 70, 435A
Yuen, 2021, Repeat dosing of the GalNAc-siRNA AB-729 in subjects with chronic hepatitis B results in robust and sustained HBsAg suppression, J Hepatol, 75, S203
Paratala, 2021, Inhibition of hepatitis B surface antigen in chronic hepatitis B subjects by RNA interference therapeutic AB-729 is accompanied by upregulation of HBV-specific T cell activation markers, J Hepatol, 75, S761
Yuen, 2021, Preliminary on-treatment data from a Phase 2 study evaluating VIR-2218 in combination with pegIFNα2a in patients with CHB, J Hepatol, 75, S738
Yuen, 2020, Hepatitis B virus (HBV) surface antigen (HBsAg) inhibition with ISIS 505358 in chronic hepatitis B (CHB) patients on stable nucleos(t)ide analogue (NA) regimen and in NA -naive CHB patients: phase 2a, randomized, double-blind, placebo-controlled study, J Hepatol, 73, S49, 10.1016/S0168-8278(20)30646-2
Hong, 2020, Combination of antisense oligonucleotides (ASOs) ALG-020572 and ALG-020576 against hepatitis B virus (HBV) improves activity and can be combined with other anti-HBV agents, Hepatology, 72, 63A
Gilmore, 2017, Antiviral activity of GS-5801, a liver-targeted prodrug of a lysine demethylase 5 inhibitor, in a hepatitis B virus primary human hepatocyte infection model, J Hepatol, 66, S690, 10.1016/S0168-8278(17)31855-X
Erken, 2018, First clinical evaluation in chronic hepatitis B patients of the synthetic farnesoid X receptor agonist EYP001, J Hepatol, 68, S488, 10.1016/S0168-8278(18)31226-1
Al-Mahtab, 2016, Safety and efficacy of nucleic acid polymers in monotherapy and combined with immunotherapy in treatment-naive Bangladeshi patients with HBeAg+ chronic hepatitis B infection, PLoS One, 11, 10.1371/journal.pone.0156667
Bazinet, 2020, Safety and efficacy of 48 Weeks REP 2139 or REP 2165, tenofovir disoproxil, and pegylated interferon Alfa-2a in patients with chronic HBV infection naive to nucleos(t)ide therapy, Gastroenterology, 158, 2180, 10.1053/j.gastro.2020.02.058
Boulon, 2020, Characterization of the antiviral effects of REP 2139 on the HBV lifecycle in vitro, Antivir Res, 183, 104853, 10.1016/j.antiviral.2020.104853
Nie, 2020, ALG-010133, a representative S-antigen transport-inhibiting oligonucleotide polymer (STOPS) effectively inhibits hepatitis B surface antigen (HBsAg) secretion in multiple hepatitis B virus (HBV) cell models, Hepatology, 72, 502A
Gane, 2021, Safety, tolerability and pharmacokinetics (PK) of single and multiple doses of ALG-010133, an S-antigen Transport Inhibiting Oligonucleotide Polymer (STOP) for the treatment of chronic hepatitis B, J Hepatol, 75, S741
Agarwal, 2020, Liver toxicity in the Phase 2 Catalyst 206 trial of inarigivir 400mg daily added to a nucleos(t)ide in HBeAg negative patients, J Hepatol, 73, S125
Yuen, 2019, Ascending dose cohort study of inarigivir - a novel RIG I agonist in chronic HBV patients: final results of the ACHIEVE trial, J Hepatol, 70, e47, 10.1016/S0618-8278(19)30084-2
Bertoletti, 2016, Adaptive immunity in HBV infection, J Hepatol, 64, S71, 10.1016/j.jhep.2016.01.026
Boni, 2012, Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues, Gastroenterology, 143, 963, 10.1053/j.gastro.2012.07.014
Rehermann, 1996, The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response, Nat Med, 2, 1104, 10.1038/nm1096-1104
Kosinska, 2015, Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck, Med Microbiol Immunol, 204, 103, 10.1007/s00430-014-0379-5
Gane, 2019, Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: a pilot study, J Hepatol, 71, 900, 10.1016/j.jhep.2019.06.028
Das, 2008, Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection, J Exp Med, 205, 2111, 10.1084/jem.20072076
Fisicaro, 2017, Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B, Nat Med, 23, 327, 10.1038/nm.4275
Lok, 2016, Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B, J Hepatol, 65, 509, 10.1016/j.jhep.2016.05.016
Boni, 2019, Combined GS-4774 and tenofovir therapy can improve HBV-specific T-cell responses in patients with chronic hepatitis, Gastroenterology, 157, 227, 10.1053/j.gastro.2019.03.044
Chinnakannan, 2020, The design and development of a multi-HBV antigen encoded in chimpanzee adenoviral and modified Vaccinia Ankara viral vectors; A novel therapeutic vaccine strategy against HBV, Vaccines (Basel), 8
Boni, 2019, HBV immune-therapy: from molecular mechanisms to clinical applications, Int J Mol Sci, 20, 10.3390/ijms20112754
Lau, 1997, Clearance of hepatitis B surface antigen after bone marrow transplantation: role of adoptive immunity transfer, Hepatology, 25, 1497, 10.1002/hep.510250631
Qasim, 2015, Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient, J Hepatol, 62, 486, 10.1016/j.jhep.2014.10.001
Lanford, 2013, GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees, Gastroenterology, 144, 1508, 10.1053/j.gastro.2013.02.003
Janssen, 2018, Safety, efficacy and pharmacodynamics of vesatolimod (GS-9620) in virally suppressed patients with chronic hepatitis B, J Hepatol, 68, 431, 10.1016/j.jhep.2017.10.027
Boni, 2018, TLR7 agonist increases responses of hepatitis B virus-specific T cells and natural killer cells in patients with chronic hepatitis B treated with nucleos(T)ide analogues, Gastroenterology, 154, 1764, 10.1053/j.gastro.2018.01.030
Janssen, 2021, Safety and efficacy of oral TLR8 agonist, selgantolimod, in viremic adult patients with chronic hepatitis B, J Hepatol, 75
Burton, 2018, Circulating and intrahepatic antiviral B cells are defective in hepatitis B, J Clin Invest, 128, 4588, 10.1172/JCI121960
Boni, 2003, Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B, J Hepatol, 39, 595, 10.1016/S0168-8278(03)00292-7
Garcia-Lopez, 2021, Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients, J Hepatol, 74, 1064, 10.1016/j.jhep.2020.11.043
Rinker, 2018, Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B, J Hepatol, 69, 584, 10.1016/j.jhep.2018.05.004
Rivino, 2018, Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation, J Clin Invest, 128, 668, 10.1172/JCI92812
Marcellin, 2019, Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection, Liver Int, 39, 1868, 10.1111/liv.14155
Hou, 2021, 3-year treatment of tenofovir alafenamide vs. Tenofovir disoproxil fumarate for chronic HBV infection in China, J Clin Transl Hepatol, 9, 324