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      最全證據(jù)!臨床治愈可顯著改善慢乙肝遠期結(jié)局

       老國幾 2020-08-07

      編者按臨床治愈的相關(guān)研究已進入深入探索階段,最近慢乙肝臨床治愈珠峰工程項目年度工作會議上也傳來喜報,從2018年珠峰項目啟動以來,已有超1400例患者實現(xiàn)臨床治愈(相關(guān)鏈接),是非常值得期待的。臨床治愈的持久性和復(fù)發(fā)因素以及臨床治愈與遠期預(yù)后的關(guān)系一直是專家和患者都關(guān)注的重點問題。肝霖君曾系統(tǒng)分析臨床治愈后慢乙肝患者持久性佳(相關(guān)鏈接)和可顯著改善遠期結(jié)局的相關(guān)內(nèi)容(相關(guān)鏈接),這期系列分享將和大家整合最新證據(jù),并進行系統(tǒng)回顧。

      為了更系統(tǒng)地了解慢乙肝臨床治愈這十余年來的進展情況,雨露肝霖將推出4篇臨床治愈系列文章,上期第3篇與大家分享了十年慢乙肝臨床治愈詳細研究結(jié)果(相關(guān)鏈接),今天最后1篇將為大家?guī)砼R床治愈可顯著改善慢乙肝遠期結(jié)局的最全證據(jù)。

      01 慢乙肝患者獲得臨床治愈后持久應(yīng)答率高

      現(xiàn)有國內(nèi)外指南均認可臨床治愈作為慢乙肝抗病毒治療的理想結(jié)局?,F(xiàn)有基于PEG IFNα的治療策略已可大大提升慢乙肝患者臨床治愈率,因此臨床治愈后的持久性和能否安全停藥也成為了大家重點關(guān)注的問題。

      最近慢乙肝臨床治愈峰會暨中國派高峰論壇第二場會議上,眾多專家也探討了這個問題,均認可慢乙肝臨床治愈后持久性佳,復(fù)發(fā)率低,復(fù)發(fā)率均< 10%(相關(guān)鏈接)。從下表的多項研究均可證實不論通過何種方式獲得臨床治愈,其持久性佳,基本維持在85%以上。

      然而,我們知道NA單藥治療的HBsAg清除率極低,僅為 1-3%(相關(guān)鏈接)。因此,慢乙肝患者若想追求高臨床治愈率和持久應(yīng)答率,應(yīng)選擇基于PEG IFNα的治療方式。

      最全證據(jù)!臨床治愈可顯著改善慢乙肝遠期結(jié)局

      02 臨床治愈可顯著改善慢乙肝患者遠期結(jié)局

      我國原發(fā)性肝癌中92%是HBV感染導(dǎo)致(相關(guān)鏈接),而慢乙肝患者的最終治療目標是改善遠期結(jié)局,如肝癌發(fā)生發(fā)展的風(fēng)險,從而提高生存率和生活質(zhì)量。肝霖君曾系統(tǒng)分析慢乙肝患者獲得HBsAg清除后肝癌發(fā)生風(fēng)險顯著降低的相關(guān)研究。

      為方便大家查看,我們匯總最新證據(jù),多項來自美國、加拿大、日本和中國的針對不同國家和地區(qū)人群的回顧性研究和薈萃研究顯示,慢乙肝患者獲得臨床治愈后5年累積肝癌發(fā)生率為1.5%左右,甚至更低,顯著低于未獲得臨床治愈的人群(> 5%)。這證實了慢乙肝患者獲得臨床治愈后可顯著改善遠期結(jié)局。

      最全證據(jù)!臨床治愈可顯著改善慢乙肝遠期結(jié)局

      參考文獻:(可上下滑動查看)

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      [2] Yip TC, Wong GL, Wong VW, et al. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients[J]. J Hepatol, 2017.

      [3] Chi H, Wong D, Peng J, et al. Durability of Response After Hepatitis B Surface Antigen Seroclearance During Nucleos(t)ide Analogue Treatment in a Multiethnic Cohort of Chronic Hepatitis B Patients: Results After Treatment Cessation[J]. Clin Infect Dis, 2017, 65(4): 680-683.

      [4] Li MH, Yi W, Zhang L, et al. Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy[J]. J Viral Hepat, 2019, 26 Suppl 1: 32-41.

      [5] Liu Y, Li H, Yan X, et al. Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B[J]. J Viral Hepat, 2019, 26 Suppl 1: 69-76.

      [6] Alawad AS, Auh S, Suarez D, et al. Durability of Spontaneous and Treatment-Related Loss of Hepatitis B s Antigen[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 700-709 e703.

      [7] Lok AS, Zoulim F, Dusheiko G, et al. Durability of Hepatitis B Surface Antigen Loss With Nucleotide Analogue and Peginterferon Therapy in Patients With Chronic Hepatitis B[J]. Hepatol Commun, 2020, 4(1): 8-20.

      [8] Han M, Jiang J, Hou J, et al. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-alpha2a: 1 year follow-up of the OSST study[J]. Antivir Ther, 2016, 21(4): 337-344.

      [9] Yip TC, Chan HL, Wong VW, et al. Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance[J]. J Hepatol. 2017 Nov;67(5):902-908.

      [10] Tateda K, Suzuki F, Kobayashi M, et al. Predictive Factors Associated with Hepatocellular Carcinoma Incidence and Mortality after Hepatitis B Surface Antigen Seroclearance in Patients with Chronic Hepatitis B. AASLD2018 abstract (oral 213).

      [11] 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.

      [12] Song C, Zhu J, Ge Z, et al. Spontaneous Seroclearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma[J]. Clin Gastroenterol Hepatol, 2019, 17(6): 1204-1206.

      [13] F. Liu, X.-W. Wang, L. Chen, 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 Jun;43(12):1253-61.

      [14] Kuang XJ, Jia RR, Huo RR, et al. Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance[J]. J Viral Hepat, 2018, 25(9): 1026-1037.

      [15] Jiang JF, Sun J, Shi J, et al. Letter: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance[J]. Aliment Pharmacol Ther. 2017 May;45(9):1286-1288.

      [16] Hannah S Choi, Ryan Anderson, Oliver Lenz, et al. Association between HBsAg loss and risk of hepatocellular carcinoma in chronic hepatitis B: a systematic review and Meta-analysis. AASLD2019. Abstracts (poster 671).

      [17] Anderson RT, et al. Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic HBV Infection: Systematic Review and Meta-analysis[J]. Clin Gastroenterol Hepatol, 2020.

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