The prognosis of hepatitis E superinfection in hospitalized chronic hepatitis B patients in China:A systematic review and Meta-analysis
SU Ying-ying and HUANG Yue contributed equally to this article
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摘要:
目的 评估中国慢性乙型肝炎(chronic hepatitis B, CHB)患者中戊型肝炎病毒(hepatitis E virus, HEV)重叠感染的发生和转归情况。 方法 检索PubMed、中国知网(CNKI)以及万方数据资源库, 收集2008-2019年中国关于CHB患者中HEV重叠感染的文献和相关文献的参考文献, 按照纳入排除标准进行文献筛选, 对纳入的文献进行数据提取、质量评价和统计分析, 使用R 3.5.2和Revman 5.3软件进行异质性检验(统计量I2)、合并率和比值比(odds ratio, OR)的计算。 结果 共纳入28篇文献。在CHB住院患者中HEV重叠感染率为13.6%(95% CI:12.5%~14.9%)。重叠感染HEV的CHB住院患者(CHB-HEV住院患者)中肝衰竭发生率为34.7%(95% CI:29.6%~40.1%), 发生风险均高于单纯CHB患者(OR=10.9, 95% CI:6.8~17.4)、重叠感染甲型肝炎病毒(hepatitis A virus, HAV)的CHB住院患者(CHB-HAV住院患者)(OR=3.8, 95% CI:2.4~6.2)以及单纯戊型肝炎患者(OR=5.1, 95% CI:3.8~6.8)。CHB-HEV住院患者病死率为13.8%(95% CI:10.3~17.8), 病死风险均高于单纯CHB患者(OR=8.5, 95% CI:4.0~18.3)、CHB-HAV住院患者(OR=14.4, 95% CI:4.8~42.9)以及单纯戊型肝炎患者(OR=4.4, 95% CI:3.0~6.4)。 结论 我国CHB住院患者中重叠感染HEV较常见, 是肝衰竭和死亡的重要诱因。 Abstract:Objective To evaluate the prevalence and prognosis of hepatitis E virus(HEV) superinfection in patients with chronic hepatitis B(CHB). Methods Electronic databases of Pubmed, CNKI, and Wanfang were searched, and references of the relevant articles for literatures associated with HEV superinfection in CHB patients in China published during 2008-2019 were screened. Studies which met the inclusion and exclusion criterias were selected and related data were pooled for analysis. The R 3.5.2 and Revman 5.3 were used to measure heterogeneity with the I2 statistic and pooled incidence and odds ratio(OR). Results 28 literatures were eligible for inclusion. The results showed the rate of HEV superinfection in hospitalized CHB(CHB-HEV) patients was 13.6%(95%CI: 12.5%-14.9%). The pooled incidence of liver failure in CHB-HEV patients was 34.7%(95%CI:29.6%-40.1%), which was higher than CHB patients(OR=10.9, 95%CI: 6.8-17.4), CHB patients superinfected with hepatitis A virus(CHB-HAV)(OR=3.8, 95%CI: 2.4-6.2), and hepatitis E patients(OR=5.1, 95%CI: 3.8-6.8). The pooled mortality of CHB-HEV patients was 13.8%(95%CI:10.3-17.8), which was higher than CHB patients(OR=8.5, 95%CI: 4.0-18.3), CHB-HAV patients(OR=14.4, 95%CI: 4.8-42.9), and hepatitis E patients(OR=4.4, 95%CI: 3.0-6.4). Conclusion In China, HEV sueperinfection on chronic hepatitis B patients are common, and is an important cause of liver failure and death. -
Key words:
- Hepatitis B /
- Chronic /
- Hepatitis E /
- Superinfection /
- Liver failure /
- Mortality
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表 1 28篇纳入文献基本信息
Table 1. Characteristic of 28 included studies
第一作者, 年份 研究类型 人群特征 结局指标 研究周期 研究地区 研究质量评价 Zhang[8], 2018 病例-对照研究 社区人群 CHB-HEV 2014.04-2014.07 山东省 高 Lai[5], 2018 回顾性队列研究 住院患者 病死 2000.01-2016.12 香港 中 赵瑞红[9], 2018 回顾性队列研究 住院患者 CHB-HEV 1995.01-2014.12 湖北省 中 孟志杰[10], 2017 回顾性队列研究 住院患者 肝衰竭、病死 2013.01-2016.01 广西省 中 张勋[11], 2017 回顾性队列研究 住院患者 肝衰竭 2012.01-2015.12 安徽省 低 Chen[12], 2016 回顾性队列研究 住院患者 肝衰竭、病死 2009.09-2014.09 上海市 低 张丹[13], 2015 回顾性队列研究 住院患者 肝衰竭、病死 2010.06-2013.06 辽宁省 中 廖宝林[14], 2015 回顾性队列研究 住院患者 肝衰竭 2005.04-2013.06 广东省 低 杜敬佩[15], 2015 回顾性队列研究 住院患者 肝衰竭、病死 2006.02-2014.04 河南省 低 周燕[16], 2014 回顾性队列研究 住院患者 肝衰竭、病死 2010.07-2013.07 上海市 中 汤曦[17], 2014 回顾性队列研究 住院患者 肝衰竭、病死 2011.01-2012.12 北京市 低 朱鹏[18], 2014 回顾性队列研究 住院患者 病死 2003.01-2013.06 重庆市 低 Chow[6], 2014 回顾性队列研究 住院患者 肝衰竭、病死 2000.11-2012.02 香港 低 贺新春[19], 2013 回顾性队列研究 住院患者 肝衰竭、病死 2009.10-2011.10 无 中 Cheng[20], 2013 回顾性队列研究 住院患者 肝衰竭、病死 2003.01-2012.01 广东省 低 刘建湘[21], 2012 回顾性队列研究 住院患者 肝衰竭、病死 2008.05-2010.10 重庆市 低 温丽珍[22], 2012 回顾性队列研究 住院患者 病死 2007.01-2011.09 安徽省 低 姚维敏[23], 2011 回顾性队列研究 住院患者 肝衰竭、病死 2005.01-2010.01 广东省 中 魏嬛[24], 2011 回顾性队列研究 住院患者 肝衰竭、病死 2004.01-2010.12 广东省 低 阎鹏[25], 2011 回顾性队列研究 住院患者 肝衰竭 2006-2009 辽宁省 低 杨涛[26], 2010 回顾性队列研究 住院患者 肝衰竭、病死 2006.01-2007.05 辽宁省 中 李蔚莉[27], 2010 回顾性队列研究 住院患者 肝衰竭、病死 2005-2009 无 中 Zhang[28], 2010 回顾性队列研究 住院患者 肝衰竭、病死 1999.03-2007.10 广东省 低 章述军[29], 2010 回顾性队列研究 住院患者 病死 2007.01-2008.12 湖北省 中 李智[30], 2009 回顾性队列研究 住院患者 肝衰竭 2005.01-2008.07 湖北省 中 章以法[31], 2008 回顾性队列研究 住院患者 肝衰竭、病死 2004.02-2008.01 江苏省 中 王文虎[32], 2008 回顾性队列研究 住院患者 肝衰竭、病死 2000.08-2006.08 湖北省 低 夏小学[33], 2008 回顾性队列研究 住院患者 肝衰竭、病死 2003.06-2008.06 浙江省 低 
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表 2 不同肝炎患者肝衰竭发生率及病死率Meta分析
Table 2. Meta-analysis for liver failure incidence and mortality in different types of patients
患者类型 文献数量(篇) 例数(人) I2值(%) 合并模型 合并率(%)(95% CI)值 肝衰竭发生率 CHB-HEV 20 1 119 68 随机效应 34.7(29.6~40.1) 单纯CHB 6 380 0 固定效应 6.1(3.7~8.9) 单纯戊肝 13 1 240 69 随机效应 6.8(4.3~9.8) CHB-HAV 3 163 29 固定效应 16.3(10.9~22.5) 病死率 CHB-HEV 22 1 563 75 随机效应 13.8(10.3~17.8) 单纯CHB 6 331 0 固定效应 1.5(0.3~3.4) 单纯戊肝 14 1 963 76 随机效应 1.8(0.6~3.6) CHB-HAV 4 248 0 固定效应 0.9(0.0~2.8)
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表 3 CHB-HEV患者与不同对照患者对比的肝衰竭、病死风险的Meta分析
Table 3. Meta-analysis for risk factor of liver failure and death in CHE-HEV superinfection group and control groups
对照患者 文献数量(篇) 例数(人)(病例, 对照)a I2值(%) 合并模型 合并OR(95% CI)值 肝衰竭发生风险 合并对照 20 1 119, 1 783 41 固定效应 5.6(4.5~7.0) CHB对照 6 310, 380 35 固定效应 10.9(6.8~17.4) 戊肝对照 13 618, 1 240 19 固定效应 5.1(3.8~6.8) CHB-HAV对照 3 296, 163 0 固定效应 3.8(2.4~6.2) 病死风险 合并对照 20 1 260, 2 543 0 固定效应 6.1(4.4~8.5) CHB对照 6 303, 331 0 固定效应 8.5(4.0~18.3) 戊肝对照 14 813, 1 963 0 固定效应 4.4(3.0~6.4) CHB-HAV对照 4 410, 248 0 固定效应 14.4(4.8~42.9) 注:a表示合并人群CHB-HEV组人数和对照组人数。
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[1] World Health Organization. Global Hepatitis Report, 2017[R]. https://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455-eng.pdf;jsessionid=2F611CABB34A7F13B2CE3E29C0C3EC1B?sequence=1 (Accessed 29 Nov, 2019). [2] Murray KF, Shah U, Mohan N, et al. Chronic hepatitis[J]. J Pediatr Gastroenterol Nutr, 2008, 47(2): 225-233. DOI: 10.1097/MPG.0b013e318181b08b. [3] Keeffe E. Hepatitis A in patients with chronic liver disease-severity of illness and prevention with vaccination[J]. J Viral Hepat, 2000, 7Suppl1: 15-17. DOI: 10.1046/j.1365-2893.2000.00016.x. [4] Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology, 2016, 63(1): 261-283. DOI: 10.1002/hep.28156. [5] Lai JC, Wong GL, Yip TC, et al. Chronic hepatitis B increases liver-related mortality of patients with acute hepatitis E: A territorywide cohort study from 2000 to 2016[J]. Clin Infect Dis, 2018, 67(8): 1278-1284. DOI: 10.1093/cid/ciy234. [6] Chow CW, Tsang SW, Tsang OT, et al. Comparison of acute hepatitis E infection outcome in patients with and without chronic hepatitis B infection: a 10 year retrospective study in three regional hospitals in Hong Kong[J]. J Clin Virol, 2014, 60(1): 4-10. DOI: 10.1016/j.jcv.2014.01.024. [7] Cota GF, de Sousa MR, Fereguetti TO, et al. Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison[J]. PLoS Negl Trop Dis, 2013, 7(5): e2195. DOI: 10.1371/journal.pntd.0002195. [8] Zhang L, Jiang Z, Lv J, et al. Comparison of hepatitis E virus seroprevalence between HBsAg-positive population and healthy controls in Shandong province, China[J]. BMC Infect Dis, 2018, 18(1): 75. DOI: 10.1186/s12879-018-2974-3. [9] 赵瑞红, 马科, 胡静, 等.大型综合性医院感染科住院肝病患者病因近20年流行病学现状[J].中华肝脏病杂志, 2018, 26(2): 136-141. DOI: 10.3760/cma.j.issn.1007-3418.2018.02.012.Zhao RH, Ma K, Hu J, et al. Current epidemiological status of causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital within the past 20 years[J]. Chin J Hepatol, 2018, 26(2): 136-141. DOI: 10.3760/cma.j.issn.1007-3418.2018.02.012. [10] 孟志杰.乙型肝炎重叠戊型肝炎患者肝功能指标及预后分析[J].临床合理用药杂志, 2017, 10(6): 165-166. DOI: 10.15887/j.cnki.13-1389/r.2017.06.079.Meng ZJ. Analysis of liver function index and prognosis in chronic hepatitis B patients superinfected with HEV[J]. Chin J of Clinical Rational Drug Use, 2017, 10(6): 165-166. DOI: 10.15887/j.cnki.13-1389/r.2017.06.079. [11] 张勋, 孙秋林, 李家斌.散发性戊型肝炎156例临床分析[J].实用肝脏病杂志, 2017, 20(6): 705-708. DOI: 10.3969/j.issn.1672-5069.2017.06.017.Zhang X, Sun QL, Li JB. Clinical features of patients with sporadic hepatitis E: ananalysis of 156 cases[J]. J Clin Hepatol, 2017, 20(6): 705-708. DOI: 10.3969/j.issn.1672-5069.2017.06.017. [12] Chen C, Zhang SY, Zhang DD, et al. Clinical features of acute hepatitis E super-infections on chronic hepatitis B[J]. World J Gastroenterol, 2016, 22(47): 10388-10397. DOI: 10.3748/wjg.v22.i47.10388. [13] 张丹, 于浩, 荣义辉. HBV慢性感染者重叠HEV感染的临床特征探讨[J].肝脏, 2015, (11): 841-843. DOI: 10.3969/j.issn.1008-1704.2015.11.001.Zhang D, Yu H, Rong YH. Clinical characteristics of HEV overlapping infection on patients with chronic HBV infection[J]. Chinese Hepatology, 2015, (11): 841-843. DOI: 10.3969/j.issn.1008-1704.2015.11.001. [14] 廖宝林, 林思炜, 施海燕, 等. 334例慢性乙型肝炎重叠感染戊型肝炎病毒患者临床特征分析[J].中华肝脏病杂志, 2015, 23(9): 697-699. DOI: 10.3760/cma.j.issn.1007-3418.2015.09.013.Liao BL, Lin SW, Shi HY, et al. Clinical feature analysis of 334 chronic hepatitis B patients coinfected with hepatitis E virus[J]. Chin J Hepatol, 2015, 23(9): 697-699. DOI: 10.3760/cma.j.issn.1007-3418.2015.09.013. [15] 杜敬佩, 赵巍峰.急性散发性戊型病毒性肝炎及乙戊重叠感染的研究[J].中国现代药物应用, 2015, 9(13): 67-68. DOI: 10.14164/j.cnki.cn11-5581/r.2015.13.036.Du JP, Zhao WF. Study on acute sporadic viral hepatitis E and hepatitis B patients coinfected with hepatitis E virus[J]. Chin J mod Drug Appl, 2015, 9(13): 67-68. DOI: 10.14164/j.cnki.cn11-5581/r.2015.13.036. [16] 周燕.慢性乙型肝炎重叠HAV、HEV感染的临床特点及疾病转归探讨[J].中国现代医生, 2014, 52(8): 34-35, 9. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zwkjzlml-yyws201408011Zhou Y. Discussion on the clinical characteristics and prognosis of chronic hepatitis B with HAV and HEV overlapping infection[J]. China Modern Doctor, 2014, 52(8): 34-35, 9. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zwkjzlml-yyws201408011 [17] 汤曦.协和医院171例急性散发型戊型病毒性肝炎临床特征分析[D].武汉: 华中科技大学, 2014.Tang X. Study on Acute Sporadic Hepatitis E of Clinical Characteristics of 171 Cases In Union Hospital[D]. Wuhan: Huazhong University of Science and Technology, 2014. [18] 朱鹏.稳定HBV感染及肝硬化重叠HEV的临床特征及IL-22水平研究[D].重庆: 第三军医大学, 2014.Zhu P. The research of clinical characters and serum levels of IL-22 in stable states of chronic HBV infection and cirrhosis overlapping with acute HEV infection[D]. Chongqing: Third Military Medical University, 2014. [19] 贺新春, 刘建湘, 蒋黎.慢性乙型肝炎重叠甲、戊型肝炎对肝功能及其预后的影响[J].中国感染控制杂志, 2013, 12(4): 278-280, 284. DOI: 10.3969/j.issn.1671-9638.2013.04.010.He XC, Liu JX, Jiang X. Impact of hepatitis A or E viral superinfection on liver function and prog, nosis of patients with chronic hepatitis[J]. Chin J Infect control, 2013, 12(4): 278-280, 284. DOI: 10.3969/j.issn.1671-9638.2013.04.010. [20] Cheng SH, Mai L, Zhu FQ, et al. Influence of chronic HBV infection on superimposed acute hepatitis E[J]. World J Gastroenterol, 2013, 19(35): 5904-5909. DOI: 10.3748/wjg.v19.i35.5904. [21] 刘建湘, 蒋黎.戊型肝炎重叠慢性乙型肝炎病毒感染临床分析[J].中国现代医学杂志, 2012, 22(24): 76-78. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgxdyxzz201224018tLiu JX, Jiang L. A study of acute hepatitis E infection super-infected with hepatitis B infection[J]. China Journal of Modern Medicine, 2012, 22(24): 76-78. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgxdyxzz201224018t [22] 温丽珍, 沈秦.戊型肝炎107例临床分析[J].安徽医学, 2012, 33(7): 874-875. DOI: 10.3969/j.issn.1000-0399.2012.07.034.Wen LZ, Shen Q. Clinical features of patients with hepatitis E: ananalysis of 107 case[J]. Anhui Yixue, 2012, 33(7): 874-875. DOI: 10.3969/j.issn.1000-0399.2012.07.034. [23] 姚维敏, 陈焰, 郭健文, 等.慢性乙肝患者重叠急性戊肝对临床转归的影响[J].临床医学工程, 2011, 18(7): 1042-1043. DOI: 10.3969/j.issn.1674-4659.2011.07.1042.Yao WM, Chen Y, Guo JW, et al. The Effects of Chronic Hepatitis B Virus Infected Patients Superinfected with Hepatitis E on Clinical Outcomes[J]. Clinical Medical & Engineering, 2011, 18(7): 1042-1043. DOI: 10.3969/j.issn.1674-4659.2011.07.1042. [24] 魏嬛, 卫敏, 高文军, 等.急性戊肝与慢性乙肝重叠感染的临床研究[J].中国实用医刊, 2011, 38(16): 31-33. DOI: 10.3760/cma.j.issn.1674-4756.2011.16.013.Wei Y, Wei M, Gao WJ, et al. Clinical study on chronic hepatitis B virus infected patients superinfected with acute hepatitis E virus[J]. Chinese Journal of Practical Medicine, 2011, 38(16): 31-33. DOI: 10.3760/cma.j.issn.1674-4756.2011.16.013. [25] 阎鹏, 王红梅.慢性乙型肝炎与戊型肝炎重叠感染的临床研究[J].中国误诊学杂志, 2011, 11(22): 5385-5386. DOI: 1009-6647(2011)22-5385-02.Yan P, Wang HM. Clinical study on chronic hepatitis B virus infected patients superinfected with hepatitis E virus[J]. Chin J Misdiagn, 2011, 11(22): 5385-5386. DOI: 1009-6647(2011)22-5385-02. [26] 杨涛, 吴兵.戊肝重叠慢性乙型肝炎病毒感染临床分析[J].中国实用医药, 2010, 5(08): 86-87. DOI: 10.3969/j.issn.1673-7555.2010.08.052.Yang T, Wu B. Clinical analysis of chronic hepatitis B virus infected patients superinfected with hepatitis E virus[J]. China Prac Med, 2010, 5(08): 86-87. DOI: 10.3969/j.issn.1673-7555.2010.08.052. [27] 李蔚莉.戊型肝炎重叠乙型肝炎感染的临床特征分析[J].中华医院感染学杂志, 2010, 20(21): 3329-3331. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhyygrxzz201021037Li WL. Analysis of the clinical characteristics of chronic hepatitis B virus infected patients superinfected with hepatitis E virus[J]. Chinese J Nosocomiol, 2010, 20(21): 3329-3331. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhyygrxzz201021037 [28] Zhang X, Ke W, Xie J, et al. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B[J]. Hepatol Int, 2010, 4(3): 615-620. DOI: 10.1007/s12072-010-9204-4. [29] 章述军.武汉地区戊型肝炎的流行病学研究[D].武汉: 华中科技大学, 2010.Zhang XJ. The study of epidemiology of hepatitis E in Wuhan region[D]. Wuhan: Huazhong University of Science and Technology, 2010. [30] 李智, 汪彤, 梁群, 等.散发性戊型肝炎89例临床分析[J].实用肝脏病杂志, 2009, 12(4): 294-295. DOI: 10.3969/j.issn.1672-5069.2009.04.023.Li Z, Wang T, Liang Q, et al. Clinical features of patients with sporadic hepatitis E: ananalysis of 89 case[J]. J Prac Hepatol, 2009, 12(4): 294-295. DOI: 10.3969/j.issn.1672-5069.2009.04.023. [31] 章以法, 冯岚, 吴东刚, 等.慢性乙型肝炎病毒感染重叠戊型肝炎病毒感染临床研究[J].中华实用诊断与治疗杂志, 2008, 22(12): 945-946. DOI: 10.3969/j.issn.1674-3474.2008.12.032.Zhang YF, Feng L, Wu DG, et al. Clinical study on chronic hepatitis B virus infected patients superinfected with hepatitis E virus[J]. J Chin Pract Diagn Ther, 2008, 22(12): 945-946. DOI: 10.3969/j.issn.1674-3474.2008.12.032. [32] 王文虎, 王鲁文, 龚作炯.湖北省散发性戊型病毒性肝炎167例临床分析[J].公共卫生与预防医学, 2007, 18(2): 24-26. DOI: 10.3969/j.issn.1006-2483.2007.02.008.Wang WH, Wang LW, Gong ZQ. Clinical features of 167 patients with sporadic viral hepatitis E in Hubd province[J]. J of Pub Health and PrevMed, 2007, 18(2): 24-26. DOI: 10.3969/j.issn.1006-2483.2007.02.008. [33] 夏小学, 程进, 刘花, 等.慢性乙型肝炎重叠戊型肝炎病毒感染的临床分析[J].国际流行病学传染病学杂志, 2008, 35(6): 389-390. DOI: 10.3760/cma.j.issn.1673-4149.2008.06.022.Xia XX, Cheng J, Liu H, et al. Clinical analysis of dlronic hepatitis B patients superinfected with hepatitis E virus[J]. Inter J Epidemiol Infect Dis, 2008, 35(6): 389-390. DOI: 10.3760/cma.j.issn.1673-4149.2008.06.022. [34] Ke WM, Li XJ, Yu LN, et al. Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China[J]. J Gastroenterol, 2006, 41(4): 347-351. DOI: 10.1007/s00535-005-1781-y. [35] Aggarwal R. Hepatitis E: clinical presentation in disease-endemic areas and diagnosis[J]. Semin Liver Dis, 2013;33(1): 30-40. DOI: 10.1055/s-0033-1338112. [36] Zhu FC, Huang SJ, Wu T, et al. Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China[J]. PloS One, 2014;9(1): e87154. DOI: 10.1371/journal.pone.0087154. -
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