The Clinical Cure Project of Chronic Hepatitis B in China

Summary

Chronic hepatitis B is a global public health problem, with nearly 700,000 deaths each year because of hepatitis B-related diseases. Recent studies have found that some patients who have used nucleot(s)ide analogues(NAs) for some period can achieve higher hepatitis B surface antigen(HBsAg) clearance rate(which is called clinical cure or functional cure) by using pegylated interferon. Patients who achieve clinical cure will further reduce liver inflammation, fibrosis and risks of liver cirrhosis and cancer in the future. This study was initiated in May 2018 and plans to recruit 30,000 eligible patients. The enrollment conditions are as follows: 1. according with the diagnosis of chronic hepatitis B in the guideline of China in 2015; 2.18-60 years old; 3. more than 1 year history of NAs therapy with HBsAg ≤1500 IU/ml, negative hepatitis e antigen and hepatitis B virus DNA\<100 IU/ml; 4. no contraindications of interferon. For the above patients, pegylated interferon was used for 1-2 years(combined with NAs for at least 3 months).The primary goal of this study is to find out the optimal treatment for clinical cure.

Timeline

Start

2018-05-16

Primary completion

2025-12-31

Completion

2026-06-30

Publications

• Background Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.
• Background Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5.
• Background Brunetto MR. A new role for an old marker, HBsAg. J Hepatol. 2010 Apr;52(4):475-7. doi: 10.1016/j.jhep.2009.12.020. Epub 2010 Jan 30. No abstract available.
• Background Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol. 2013 May;58(5):853-60. doi: 10.1016/j.jhep.2012.12.006. Epub 2012 Dec 13.
• Background Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, Chen DS, Kao JH. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011 Aug;141(2):517-25, 525.e1-2. doi: 10.1053/j.gastro.2011.04.046. Epub 2011 Apr 28.
• Background Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009 Jun;50(6):1084-92. doi: 10.1016/j.jhep.2009.01.016. Epub 2009 Mar 9.
• Background Dietary effects on diurnal variation in lipogenesis. Nutr Rev. 1987 May;45(5):157-8. doi: 10.1111/j.1753-4887.1987.tb06353.x. No abstract available.
• Background European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20. No abstract available.
• Background Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology. 2010 Jun;51(6):1933-44. doi: 10.1002/hep.23571.
• Background Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.
• Xie C, Lin B, Mo Z, Fu L, Chen X, Yang J, Li G, Li J, Zeng Y, Gong G, Zhang W, Tang H, Guo Y, Wei J, Jiang J, Wu X, Lv R, Lin M, Yu Z, Shang J, Guan Y, Li J, Zhang L, Guo Q, Ye Q, Mao Q, Li Y, Xue X, Geng J, Mao X, Lian J, Lu X, Hu G, Bai H, Cai D, Liu Y, Zhang L, Mao Q, Li J, Chen H, Chang J, Li Q, Xie D, Deng H, Xu Q, Peng L, Yang X, Zhuang H, Gao Z. Peginterferon alpha-2b Enhances Hepatitis B Surface Antigen Loss in Nucleos(t)ide Analogue-Suppressed Low Hepatitis B Surface Antigen Chronic Hepatitis B Patients: Everest Study in China. Clin Gastroenterol Hepatol. 2026 Feb 2:S1542-3565(26)00057-1. doi: 10.1016/j.cgh.2026.01.029. Online ahead of print.
• Chang LJ, Hao CQ, Rao GR, Xu LL, Li J, Cheng Y, Zheng LJ, Wu CW, Chen HX, Chen ZR, Lian JQ, Wu SH, Luo LM, Zhang WL, Zhang Y. Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-alpha-2b-based therapy: a multicenter pilot study. Virol J. 2025 May 19;22(1):146. doi: 10.1186/s12985-025-02761-3.
• Wang Z, Wang X, Zhou L, Shi S, Hua Y, Feng Y. Safety and efficacy of 48-week pegylated interferon-alpha-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study. Front Med (Lausanne). 2024 Dec 4;11:1489671. doi: 10.3389/fmed.2024.1489671. eCollection 2024.
• Huang Q, Xiao X, Zhuang X, Chen W, Huang Y, Liao J, Wang W, Wang Y, Lu L, Liu Z, Huang J. Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients. Viral Immunol. 2023 Apr;36(3):209-221. doi: 10.1089/vim.2022.0130. Epub 2023 Mar 21.

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