聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎部分应答患者序贯替比夫定治疗疗效观察*

doi:10.3969/j.issn.1672-5069.2020.01.009

摘要/Abstract

摘要： 目的探讨在聚乙二醇干扰素α-2a治疗的HBeAg阳性慢性乙型肝炎(CHB)部分应答患者序贯替比夫定继续治疗的临床疗效。方法 2016年1月～2017年2月我院感染病科收治的63例HBeAg阳性CHB患者在应用聚乙二醇干扰素α-2a治疗48周后呈部分应答的患者,其中31例在停止干扰素治疗后接受替比夫定序贯治疗48周,另32例则停药观察48周。两组随访24周。结果在治疗或观察24周、48周和随访24周,序贯治疗组患者血清HBeAg转阴率分别为22.5%、25.8%和35.4%,均显著高于停药观察组的0.0%、3.2%和3.2%(P<0.05),在治疗或观察48周和随访24周,序贯治疗组血清HBV DNA转阴率为90.3%和87.0%,显著高于停药观察组的34.3%和18.7%(P<0.05),ALT复常率为96.7%和90.3%,显著高于停药观察组的75.0%和25.0%(P<0.05);在治疗或观察48周和随访24周,序贯治疗组血清HBV DNA水平为(2.6±0.3)lgIU/mL和(1.9±0.1)lgIU/mL,显著低于停药组的【(4.5±0.7)lgIU/mL和(5.5±0.2)lgIU/mL,P<0.05】,血清ALT水平分别为(56.3±2.4)IU/L和(43.3±3.1)IU/L,显著低于停药组【分别为(60.1±7.2)IU/L和(71.3±2.8)IU/L,P<0.05】,在随访24周,序贯治疗组血清HBsAg水平为(2.0±0.2)lg IU/mL,显著低于停药组【(2.6±0.3)lg IU/mL,P<0.05】;序贯治疗组在48周治疗期间,其中9例(29.0%)患者在服用替比夫定期间出现血清肌酸激酶升高现象,在治疗10～13周后下降至正常水平。结论对于经聚乙二醇干扰素α-2a治疗结束后呈部分应答的血清HBeAg阳性CHB患者序贯应用替比夫定继续治疗48周,发现能够有效提高患者血清HBV DNA转阴率和ALT复常率,且安全性较高。

关键词: 慢性乙型肝炎, 聚乙二醇干扰素α-2a, 部分应答, 替比夫定, 疗效

Abstract: Objective This study was aimed to explore the clinical efficacy of sequential telbivudine treatment in serum HBeAg-positive chronic hepatitis B patients with partial response to standardized pegylated interferon alpha-2a therapy. Methods 63 patients with HBeAg-positive chronic hepatitis B were recruited in this study between January 2016 and February 2017 who had been treated with pegylated interferon alpha-2a for 48 weeks, and got partial response to the regimen. Out of them, 31 received tibivudine for further 48 week treatment, and 32 discontinued any treatment. All the patients were followed-up for 24 weeks. Results At week 24, week 48 of treatment and 24 week follow-up, the serum HBeAg negative rates in sequential treatment group were 22.5%, 25.8% and 35.4%, significantly higher than 0.0%, 3.2% and 3.2%(P<0.05) in patients who discontinued any treatment, at treatment or observation week 48 and follow-up week 24, serum HBV DNA negative rates in sequential treatment patients were 90.3% and 87.0%, significantly higher than 34.3% and 18.7%(P<0.05) in the control, and serum alanine aminotransaminase normalization rates in patients with sequential treatment were 96.7% and 90.3%, significantly higher than 75.0% and 25.0%(P<0.05) in the latter; at treatment or observation week 48 and follow-up week 24, serum HBV DNA level in patients with sequential treatment were (2.6±0.3)lg IU/mL and (1.9±0.1)lg IU/mL, siginificantly lower than 【(4.5±0.7)lgI U/mL and (5.5±0.2)lgIU/mL, P<0.05】, serum ALT level were (56.3±2.4)IU/L and (43.3±3.1)IU/L, significantly lower than 【(60.1±7.2)IU/L and (71.3±2.8)IU/L,respectively, P<0.05】 in the control, and at follow-up week 24, serum HBsAg level in patients receiving telbivudine was (2.0±0.2)lg IU/mL, significantly lower than 【(2.6±0.3)lg IU/mL, P<0.05】 in the control; 9 patients(29.0%)had transient serum CK elevation and got back to normal during telbivudine treatment. Conclusion The sequential administration of telbivudine for further treatment might effectively improve the negative serum conversion rate of HBeAg and HBV DNA in patients with HBeAg-positive chronic hepatitis B after failed pegylated interferon alpha-2a treatment.

Key words: Hepatitis B, Pegylated interferon alpha-2a, Partial response, Telbivudine, Efficacy

丁俊琪, 张偲, 张彬. 聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎部分应答患者序贯替比夫定治疗疗效观察^*[J]. 实用肝脏病杂志, 2020, 23(1): 26-29.

Ding Junqi, Zhang Cai, Zhang Bin. Therapeutic effect of sequential telbivudinetreatment in serum HBeAg-positive chronic hepatitis B patients with partial response to pegylated interferon alpha-2a regimen[J]. Journal of Practical Hepatology, 2020, 23(1): 26-29.

参考文献

[1] Stasi C, Silvestri C, Voller F. Emerging trends in epidemiology of hepatitis B virus infection. J Clin Transl Hepatol, 2017, 5(3):272-276.
[2] Sarin SK. Asian-pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int, 2016, 10(1):1-98.
[3] Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology, 2016, 63(1):261-283.
[4] Lu LG. Antiviral therapy of liver cirrhosis related to hepatitis B virus infection. J Clin Transl Hepatol, 2015, 2(3):197-201.
[5] Okoronkwo N, Wang Y, Pitchumoni C, et al. Improved outcomes following hepatocellular carcinoma (HCC) diagnosis in patients screened for HCC in a large academic liver center versus patients identified in the community. J Clin Transl Hepatol, 2017, 5(1):31-34.
[6] Jiang H, Wang J, Zhao W. Lamivudine versus telbivudine in the treatment of chronic hepatitis B: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis, 2013, 32(1):11-18.
[7] Lee M, Oh S, Lee HJ, et al. Telbivudine protects renal function in patients with chronic hepatitis B infection in conjunction with adefovir-based combination therapy. J Viral Hepat, 2013, 21(12):873-881.
[8] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[9] Lampertico P, Vigano M, Di Costanzo GG, et al.Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut, 2013, 62(2):290-298.
[10] Sun J, Ma H, Xie Q, et al. Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: a randomized controlled study. J Hepatol, 2016, 65(4):674-682.
[11] 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 Viral Hepat, 2013, 20(4):11-19.
[12]罗晓丹,陈小苹,陈仁,等.聚乙二醇干扰素α-2a治疗HBeAg阳性CHB24周应答不佳患者序贯替比夫定及恩替卡韦104周疗效观察.中华肝脏病杂志, 2016, 24(4):241-245.
[13]杨小安,舒欣,张英,等.聚乙二醇干扰素治疗效果不佳的HBeAg阳性慢乙型肝炎患者序贯替比夫定治疗的疗效观察.中华实验和临床病毒学杂志, 2014, 28(5):364-366.
[14] Gane EJ, Deray G, Liaw YF, et al. Telbivudine improves renal function in patients with chronic hepatitis B. Gastroenterology, 2014, 146(1):138-146.
[15] Huang Z, Zhao Z, Zheng Y, et al. Efficacy of sequential use of telbivudine in hepatitis B e antigen-positive chronic hepatitis B patients with partial responses to pegylated interferon: a pilot study. J Viral Hepat, 2013, 20(1):52-57.
[16] 张滢,郑琦,陈靖,等.替比夫定序贯聚乙二醇干扰素α治疗HBeAg阳性CHB部分应答者的疗效.中华肝脏病杂志, 2018, 26(2):102-107.
[17] Piccolo P, Lenci I. A randomized controlled trial of sequential pegylated interferon-α and telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic hepatitis B. Antivir Ther, 2013, 18(1):57-64.
[18] Luo XD, Chen XF, Zhou Y, et al. Comparison of 208‐week sequential therapy with telbivudine and entecavir in HBeAg‐positive chronic hepatitis B patients with suboptimal responses to 24weeks of Peg‐IFNα‐2a therapy: An open‐labelled, randomized, controlled, “real‐life” trial. J Viral Hepat, 2017, 24(1):36-42.
[19] An J, Lim YS, Kim GA, et al. Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial. BMC Gastroenterol, 2017, 17(1):15-21.
[20] Kao JH, Asselah T, Dou XG, et al. Telbivudine therapy for chronic hepatitis B: A journey to identify super‐responders and to optimize treatment using the roadmap model. J Gastroenterol Hepatol, 2017, 32(1):73-81.
[21] Katoonizadeh A, Motamed-Gorji N, Sharafkhah M,et al. Intra-familial Transmission of Chronic Hepatitis B Infection: A Large Population-Based Cohort Study in Northern Iran.Arch Iran Med, 2018,21(10):436-442.
[22] Bulathsinhala BKS, Siriwardana RC, Gunetilleke MB,et al. Clinical characteristics and outcomes of hepatocellular carcinoma: results from prospective study, from a tertiary referral center in 8136 A 636 Sri Lanka. Ceylon Med J, 2018,63(3):133-138.
[23] Aslam A, Campoverde Reyes KJ, Malladi VR, et al. Management of chronic hepatitis B during pregnancy. Gastroenterol Rep (Oxf), 2018,6(4):257-262.

聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎部分应答患者序贯替比夫定治疗疗效观察^*

Therapeutic effect of sequential telbivudinetreatment in serum HBeAg-positive chronic hepatitis B patients with partial response to pegylated interferon alpha-2a regimen

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