不同抗病毒策略治疗慢性乙型肝炎低病毒血症临床疗效的Meta分析-现代医学

不同抗病毒策略治疗慢性乙型肝炎低病毒血症临床疗效的Meta分析

单位：1. 湖北中医药大学中医临床学院, 湖北武汉 430065;
2. 江汉大学附属湖北省第三人民医院中西医结合肝病科, 湖北武汉 430033

分类号：R512.6

出版年·卷·期（页码）：2023·51·第十二期（1661-1667）

摘要：

目的：运用Meta分析方法评价不同抗病毒策略治疗慢性乙型肝炎经治后低病毒血症(LLV)的临床疗效。方法：检索PubMed、Embase、Web of Science、中国知网(CNKI)、万方知识服务平台(WanFang Data)文献数据库，选取符合纳入标准的治疗慢性乙型肝炎LLV的临床研究文献，使用Rev Man 5.4.1软件进行统计学分析。结果：本研究纳入8篇文献，涉及1 150例患者，经Meta分析后提示与维持原核苷类药物(NAs)治疗相比，换用新NAs的治疗方案可以获得更高的HBV DNA阴转率[RR=5.49，95%CI(3.73,8.08)，P<0.01]以及HBeAg清除率[RR=2.77，95%CI(1.33,5.77)，P= 0.006]；含有长效干扰素(PEG-IFN)治疗方法可以获得更高的HBsAg清除率,差异有统计学意义[RR=8.29，95%CI(1.01,68.33)]；不同治疗策略谷丙转氨酶(ALT)复常率差异无统计学意义(P＞0.05)。在含有PEG-IFN治疗策略组中，治疗相关不良事件发生率更高[RR=6.42，95%CI(1.69,24.36)，P<0.05]。结论：不同抗病毒策略安全性均较高，换用新NAs治疗可以提高LLV患者HBV DNA阴转率和HBeAg消除率。

Objective: Meta analysis was used to evaluate the clinical efficacy of different antiviral strategies for the treatment of treated chronic hepatitis B with low-level viremia(LLV). Methods: The literature databases of PubMed, Embase, Web of Science, CNKI and WanFang Data were searched, and the clinical research literatures on the treatment of chronic hepatitis B hypoviremia LLV were selected and statistically analyzed by RevMan5.4.1 software. Results: This study included 8 literatures involving 1 150 patients. Meta analysis suggested that compared with maintaining pronucleoside drugs(NAs), the new NAs treatment regimen could achieve higher HBVDNA negative conversion rate [RR=5.49,95%CI(3.73,8.08), P<0.01] and higher HBeAg clearance rate [RR=2.77,95%CI(1.33,5.77), P=0.006]. Treatment with long-acting interferon(PEG-IFN) could achieve HBsAg clearance rate(9/241), however, the difference was not statistically significant[RR=8.29,95%CI(1.01,68.33), P=0.05], and there was no significant difference in ALT normalization rate among different treatment strategies(P>0.05). The incidence of treatment-related adverse events was higher in the group with PEG-IFN treatment strategy [RR=6.42，95%CI(1.69,24.36)，P＜0.05]. Conclusion: The safety of different antiviral strategies was high, switching to new NAs treatment can increase the negative conversion rate of HBVDNA and HBeAg clearance rate in patients with LLV, and the treatment regimen containing PEG-IFN can increase the dearamce rate of HBsAg.

参考文献：

[1] HUANG D Q,LI X,LE M H,et al.Natural history and hepatocellular carcinoma risk in untreated chronic hepatitis B patients with indeterminate phase[J].Clin Gastroenterol H,2022,20(8):1803-1812.
[2] 中华医学会感染病学分会,中华医学会肝病学分会.慢性乙型肝炎防治指南(2022版)[J].中华肝脏病杂志,2022,30(12):1309-1331.
[3] ZHANG Q,CAI D C,HU P,et al.Low-level viremia in nucleoside analog-treated chronic hepatitis B patients[J].Chin Med J(Engl),2021,134(23):2810-2817.
[4] LEE S B,JEONG J,PARK J H,et al.Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir[J].Clin Mol Hepatol,2020,26(3):364-365.
[5] WILLEM P B,QING X,MILAN J S,et al.Adding peginterferon to entecavir for HBeAg-positive chronic hepatitis B:a multicenter randomized trial(ARES study)[J].Hepatology,2015,61(5):p1512-1522.
[6] HAMAD A A,MUSTGAFA C P,MOHAMMED A Q,et al.HBsAg clearance in chronic hepatitis B patients with addon pegylated interferon alfa2a to ongoing tenofovir treatment:a randomized controlled study[J].Saudi J Gastroenterology,2017,23(3):190-198.
[7] HYUNG J Y,IN H K,SANG J S,et al.Switching to tenofovir vs continuing entecavir for HBV with partial virologic response to entecavir:a randomized controlled trial[J].J Viral Hepatitis,2018,11:351-356.
[8] 胡鹏,尚佳,张文宏,等.核苷酸类似物治疗部分应答的乙型肝炎患者通过聚乙二醇干扰素α-2a治疗获得HBsAg消失:New Switch研究[J].中华肝脏病杂志,2018,26(10):756-764.
[9] NING Q,HAN M,SUN Y,et al.Switching from entecavir to PeglFNalfa-2a in patients with HBeAg-positive chronic hepatitis B:a randomised open-label trial(OSST trial)[J].J Hepatol,2014,61(4):777-784.
[10] HENG C,BETTINA E H,SIMIN G,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(1):1085-1093.
[11] ZHONG B L,LE L,XIAO X N,et al.Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia[J].Liver Int,2021,3(1):1-12.
[12] 程海林,胡旭东,夏冰,等.富马酸丙酚替诺福韦对恩替卡韦经治后低病毒载量的慢性乙型肝炎患者的临床疗效[J].临床肝胆病杂志,2022,38(3):537-540.
[13] TERRAULT N A,LOK A S F,MCMAHON B J,et al.Update on prevention,diagnosis,and treatment of chronic hepatitis B:AASLD 2018 hepatitis B guidance[J].Hepatology,2018,67(4):1560-1599.
[14] European Association for the Study of the Liver.EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J].J Hepatol,2017,67(2):370-398.
[15] SINN D H,LEE J,GOO J,et al.Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load[J].Hepatology,2015,62(3):694-701.
[16] 鲁凤民,封波,郑素军,等.核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的研究现状[J].临床肝胆病杂志,2021,37(6):1268-1270.
[17] KIM J H,SINN D H,KANG W,et al.Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J].Hepatology,2017,66:335-343.
[18] KIM T S,SINN D H,KANG W,et al.Hepatitis B virus DNA levels and overall survival in hepatitis B related hepatocellular carcinoma patients with low-level viremia[J].J Gastroenterol Hepatol,2019,34(2):2028-2035.
[19] JANSSEN H L,SONNEVELD M J,BRUNETTO M R.Quantification of serum hepatitis B surface antigen:is it useful for the management of chronic hepatitis B?[J].Gut,2012,61(5):641-645.
[20] WIELAND S F,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.
[21] YIN G Q,LI J,ZHONG B,et al.New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:increase of entecavir dosage[J].World J Gastroenterol,2021,27(8):666-676.

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