Objective To investigate the clinical significance of co-infection with hepatitis B virus ( HBV) and Epstein-Barr virus ( EBV) in HBV-related liver diseases such as chronic hepatitis B ( CHB) , liver cirrhosis, and hepatocellular carcinoma ( HCC) . Methods A retrospective analysis was performed for the clinical data of 487 patients with HBV infection who were diagnosed in Zhongnan Hospital of Wuhan University from May 2016 to August 2018, among whom 194 ( 39. 8%) had co-infection with HBV and EBV. The patients were divided into groups according to the copy number of EBV DNA ( > 400 IU/ml) , Child-Pugh class ( Child-Pugh class A, B, and C) , and progression of liver disease ( CHB, liver cirrhosis, and HCC) , and related indices were compared between groups. The t-test was used for comparison of normally distributed continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Dunn-Bonferroni test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Results The patients with CHB had a significantly higher copy number of HBV-DNA than those with liver cirrhosis or HCC ( t = 2. 417 and 3. 258, P = 0. 017 and 0. 001) , while the patients with HCC tended to have a higher copy number of EBV DNA than those with CHB or liver cirrhosis, but there was no significant difference between the three groups ( F = 1. 161, P = 0. 315) . After adjustment for liver function based on Child-Pugh class, the HCC patients with Child-Pugh class A liver function had a significantly higher copy number of EBV DNA than the CHB patients and the patients with liver cirrhosis ( t = 2. 062 and 2. 615, P = 0. 041 and 0. 010) , the liver cirrhosis patients with Child-Pugh class C liver function had a significantly higher copy number of EBV DNA than the CHB patients ( t = 2. 647, P = 0. 012) . ALT/AST, globulin, and lymphocyte percentage were specific clinical indices for co-infection with HBV and EBV. Conclusion There is an increase in EBV load in HCC patients, and both EBV and HBV are involved in the progression of liver diseases. Dynamic quantification of EBV DNA in patients with HBV infection has a certain significance in early intervention of the progression of liver diseases.
[1]TREPO C, CHAN H L, LOK A. Hepatitis B virus infection[J].Lancet, 2014, 384 (9959) :2053-2063.
|
[2]SCHWEITZER A, HORN J, MIKOLAJCZYK RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection:A systematic review of data published between 1965 and2013[J]. Lancet, 2015, 386 (10003) :1546-1555.
|
[3]ELGUI DE OLIVEIRA D, MULLER-COAN BG, PAGANO JS.Viral carcinogenesis beyond malignant transformation:EBV in the progression of human cancers[J]. Trends Microbiol, 2016, 24 (8) :649-664.
|
[4]RAO SC, ASHRAF I, MIR F, et al. Dual infection with hepatitis B and Epstein-Barr virus presenting with severe jaundice, coagulopathy, and hepatitis B virus chronicity outcome[J]. Am J Case Rep, 2017, 18:170-172.
|
[5]HUANG JW, HAN FZ. A clinical study of chronic hepatitis B patients with Epstein-Barr virus infection[J]. J Clin Hepatol, 2018, 34 (8) :1659-1663. (in Chinese) 黄姜伟, 韩方正.慢性乙型肝炎重叠EB病毒感染的临床观察[J].临床肝胆病杂志, 2018, 34 (8) :1659-1663.
|
[6]LI M. Investigation and characteristics of Epstein-Barr virus infection among patients with different liver diseases[D].Changchun:Jilin University, 2016. (in Chinese) 李敏.不同肝病Epstein-Barr virus感染的调查及临床特点分析[D].长春:吉林大学, 2016.
|
[7]Experts in combined team of the Major Special Project of Ministry of Science and Technology supported by China’s“Twelfth Five-Year Plan”. Management of clinical diagnosis, evaluation, and antiviral therapy for HBV-related cirrhosis[J]. J Clin Hepatol, 2014, 30 (2) :99-108. (in Chinese) 科技部十二五重大专项联合课题组专家.乙型肝炎病毒相关肝硬化的临床诊断、评估和抗病毒治疗的综合管理[J].临床肝胆病杂志, 2014, 30 (2) :99-108.
|
[8]DONG H, CONG WM. Increasing the standardized pathology diagnosis level of primary hepatocellular carcinoma, escorting clinical precised treatment——Interpretation of"Guidelines for the diagnosis of primary hepatocellular carcinoma (2015) "[J]. Chin J Gen Surg, 2016, 25 (7) :939-943. (in Chinese) 董辉, 丛文铭.提高肝癌规范化病理诊断水平, 为临床精细化治疗保驾护航——《原发性肝癌规范化病理诊断指南 (2015年版) 》解读[J].中国普通外科杂志, 2016, 25 (7) :939-943.
|
[9]WANG GQ, WANG FS, CHENG J, et al. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 王贵强, 王福生, 成军, 等.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.
|
[10]The State Health and Family Planning Commission of the People's Republic of China. Diagnosis, management, and treatment of hepatocellular carcinoma (V2017) [J]. J Clin Hepatol, 2017, 33 (8) :1419-1431. (in Chinese) 中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范 (2017年版) [J].临床肝胆病杂志, 2017, 33 (8) :1419-1431.
|
[11]GUPTA E, BALLANI N, KUMAR M, et al. Role of non-hepatotropic viruses in acute sporadic viral hepatitis and acute-on-chronic liver failure in adults[J]. Indian J Gastroenterol, 2015, 34 (6) :448-452.
|
[12]SINHA M, RAO CR, PREMALATA CS, et al. Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas:Two lymphotropic, potentially oncogenic, latently occurring DNA viruses[J]. Indian J Med Paediatr Oncol, 2016, 37 (3) :146-151.
|
[13]TSENG TC, HUANG LR. Immunopathogenesis of Hepatitis B Virus[J]. J Infect Dis, 2017, 216 (suppl 8) :s765-s770.
|
[14]GUPTA E, BHATIA V, CHOUDHARY A, et al. Epstein-Barr virus associated acute hepatitis with cross-reacting antibodies to other herpes viruses in immunocompetent patients:report of two cases[J]. J Med Virol, 2013, 85 (3) :519-523.
|
[15]YANG C, LI N, WANG Y, et al. Serum levels of B-cell activating factor in chronic hepatitis B virus infection:Association with clinical diseases[J]. J Interferon Cytokine Res, 2014, 34 (10) :787-794.
|
[16]YANG YQ, ZHANG H, LI X, et al. Clinical study on the relationship between EBV infection and liver diseases infected by HBV[J/CD]. Chin J Liver Dis:Electronic Edition, 2015, 7 (4) :90-93. (in Chinese) 杨玉奇, 张慧, 李昕, 等.乙型肝炎、丙型肝炎合并EB病毒感染与肝硬化发生的横断面研究[J/CD].中国肝脏病杂志:电子版, 2015, 7 (4) :90-93.
|
[17]LI W, WU BA, ZENG YM, et al. Epstein-Barr virus in hepatocellular carcinogenesis[J]. World J Gastroenterol, 2004, 10 (23) :3409-3413.
|
[18]ONOZAWA E, SHIBAYAMA H, IMADOME KI, et al. Inflammatory cytokine production in chronic active Epstein-Barr virus infection[J]. Rinsho Ketsueki, 2017, 58 (3) :189-196.
|
[19]PETROVA M, KAMBUROV V, NIKOLOVSKA D, et al. Epstein-Barr virus:Is there any contribution to chronic hepatitis B and C?[J]. Liver Int, 2010, 30 (3) :488-489.
|
[20]YANG YD, LIN Q. Analysis on the virus markers and liver function of patients with EBV-Ig M positive[J/CD]. Chin J Exp Clin Infect Dis:Electronic Edition, 2014, 8 (6) :785-788. (in Chinese) 杨友道, 林青. EB病毒抗-VCA IgM阳性患者病毒标志物及肝功能检查结果分析[J/CD].中华实验和临床感染病杂志:电子版, 2014, 8 (6) :785-788.
|
[21]WU T, ZHENG X, YANG M, et al. Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients[J]. Sci Rep, 2017, 7:42710.
|
[22]AN H, ZHOU XJ, MIAO CM. Clinical study on the relationship between EBV infection and liver diseases infected by HBV[J].Chin J Integr Tradit West Med Liver Dis, 2005, 15 (3) :144-145. (in Chinese) 安辉, 周小军, 缪灿铭. EB病毒感染与乙肝病毒相关性肝病关系的临床研究[J].中西医结合肝病杂志, 2005, 15 (3) :144-145.
|