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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 5
May  2018
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Association of HBV precore/core promoter variants with the degree of liver fibrosis in patients with HBeAg-positive chronic hepatitis B

DOI: 10.3969/j.issn.1001-5256.2018.05.019
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  • Received Date: 2017-11-22
  • Published Date: 2018-05-20
  • Objective To investigate the association of hepatitis B virus ( HBV) precore/core promoter variants with liver pathological changes in patients with HBe Ag-positive chronic hepatitis B ( CHB) . Methods A total of 148 HBe Ag-positive CHB patients who were hospitalized in Guangzhou Eighth People's Hospital from April 2012 to December 2013, underwent liver biopsy, and had stored frozen serum samples were enrolled. Serum DAN was extracted and then nested PCR was used for the multiplication and sequencing of the HBV precore/core promoter region. The Mann-Whitney U test was used for comparison of continuous data with heterogeneity of variance between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was performed to identify the parameters associated with marked liver fibrosis. Results Of all patients, 116 ( 78. 4%) were found to have marked liver fibrosis ( ≥S2) by liver biopsy. Among the patients with ALT ≤upper limit of normal, 10 ( 58. 8%) had marked liver fibrosis; 11. 8% had T1753 V mutation, 35. 3% had A1762 T/G1764 A mutation, and 5. 9% had G1896 A mutation. The univariate logistic regression analysis showed that HBV A1762 T/G1764 A and G1896 A mutations were significantly associated with marked liver fibrosis ( P < 0. 05) , while age, sex, HBV genotype, and other HBV mutations were not associated with marked liver fibrosis. The multivariate logistic regression analysis showed that HBV A1762 T/G1764 A mutation ( odds ratio [OR]= 7. 098, P < 0. 001) and G1896 A mutation ( OR = 16. 816, P = 0. 007) were independently associated with marked liver fibrosis. Conclusion HBV precore/core promoter variants can be used as the risk factors for marked liver fibrosis in HBe Ag-positive CHB patients.

     

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  • [1]LEE YA, WALLACE MC, FRIEDMAN SL.Pathobiology of liver fibrosis:a translational success story[J].Gut, 2015, 64 (5) :830-841.
    [2]XU MC, ZHANG F, ZHUGE YZ.Current research status of mechanisms of the development and progression of liver fibrosis[J].J Clin Hepatol, 2016, 32 (9) :1806-1809. (in Chinese) 徐明翠, 张峰, 诸葛宇征.肝纤维化发生发展机制的研究现状[J].临床肝胆病杂志, 2016, 32 (9) :1806-1809.
    [3]ACHARYA C, SAHINGUR SE, BAJAJ JS.Microbiota, cirrhosis, and the emerging oral-gut-liver axis[J].JCI Insight, 2017, 2 (19) :94416.
    [4]MANN DA.Epigenetics in liver disease[J].Hepatology, 2014, 60 (4) :1418-1425.
    [5]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.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.
    [6]POLLICINAO T, CACCIOLA I, SAFFIOTI F, et al.Hepatitis B virus Pre S/S gene variants:pathobiology and clinical implications[J].J Hepatol, 2014, 61 (2) :408-417.
    [7]ZHOU HY, LUO Y, CHEN WD, et al.Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence:A systematic review and meta-regression analysis[J].J Gastroenterol Hepatol, 2015, 30 (6) :977-983.
    [8]LIN CL, KAO JH.Hepatitis B virus genotypes and variants[J].Cold Spring Harb Perspect Med, 2015, 5 (5) :a021436.
    [9]Chinese Society of Infectious Diseases and Parasitology, Chinese Society of Hepatology, Chinese Medical Association.Prevention and treatment of viral hepatitis[J].Chin J Hepatol, 2000, 8 (6) :324-329. (in Chinese) 中华医学会传染病与寄生虫病学分会, 肝病学分会.病毒性肝炎防治方案[J].中华肝脏病杂志, 2000, 8 (6) :324-329.
    [10]XIAO L, ZHOU B, GAO H, et al.Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is associated with hepatitis B related acute-on-chronic liver failure[J].J Med Virol, 2011, 83 (9) :1544-1550.
    [11]ZHAO ZG, HAN T, GAO YT, et al.Analysis of hepatitis B virus mutations in 20 patients with HBV-related acute-on-chronic liver failure and 19 patients with chronic hepatitis B[J].Chin J Hepatol, 2014, 22 (3) :228-231. (in Chinese) 赵振刚, 韩涛, 高英堂, 等.39例慢性乙型肝炎及相关性慢加急性肝衰竭患者多基因区变异位点分析[J].中华肝脏病杂志, 2014, 22 (3) :228-231.
    [12]MA XY, HAN T, PEI YZ, et al.Analysis of the relationship between hepatitis B virus precore and basal core promoter mutations and acute-on-chronic liver failure[J].Chin J Hepatol, 2012, 20 (9) :644-648. (in Chinese) 马晓艳, 韩涛, 裴彦祯, 等.乙型肝炎病毒前C区/BCP区变异与慢加急性肝衰竭的关系[J].中华肝脏病杂志, 2012, 20 (9) :644-648.
    [13]NIAN X, XU Z, LIU Y, et al.Association between hepatitis B virus basal core promoter/precore region mutations and the risk of hepatitis B-related acute-on-chronic liver failure in the Chinese population:an updated meta-analysis[J].Hepatol Int, 2016, 10 (4) :606-615.
    [14]XIAN YC, CHENG SQ.Research and application progress of hepatitis B virus genotyping[J].Int J Virol, 2016, 32 (4) :285-288. (in Chinese) 冼永超, 程书权.乙肝病毒基因分型研究及应用进展[J].国际病毒学杂志, 2016, 32 (4) :285-288.
    [15]TONG MJ, HSU L, HSIEN C, et al.A comparison of hepatitis B viral markers of patients in different clinical stages of chronic infection[J].Hepatol Int, 2010, 4 (2) :516-522.
    [16]ZHENG JX, ZENG Z, ZHENG YY, et al.Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients[J].J Viral Hepat, 2011, 18 (10) :e423-e431.
    [17]TSENG TC, LIU CJ, YANG HC, et al.Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers[J].Gut, 2015, 64 (2) :292-302.
    [18]CHAN HL, TSANG SW, LIEW CT, et al.Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBe Ag-negative chronic hepatitis B virus infection[J].Am J Gastroenterol, 2002, 97 (2) :406-412.
    [19]LIAO BL, LIN SW, CHEN WL, et al.Analysis on relationship between HBV precore/core promoter region and the liver histological changes in HBe Ag negative CHB patients[J].J Practical Med, 2016, 32 (14) :2347-2350. (in Chinese) 廖宝林, 林思炜, 陈伟烈, 等.HBV前C/C基因启动子区变异与HBe Ag阴性CHB患者肝组织病理变化的关系[J].实用医学杂志, 2016, 32 (14) :2347-2350.
    [20]LIAO B, WANG Z, LIN S, et al.Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT[J].PLo S One, 2013, 8 (10) :e78672.
    [21]DUCANCELLE A, PIVERT A, BERTRAIS S, et al.Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity[J].J Gastroenterol Hepatol, 2016, 31 (10) :1750-1756.
    [22]BUCKWOLD VE, XU Z, CHEN M, et al.Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication[J].J Virol, 1996, 70 (9) :5845-5851.
    [23]PAREKH S, ZOULIM F, AHN SH, et al.Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants[J].J Virol, 2003, 77 (12) :6601-6612.
    [24]OZASA A, TANAKA Y, ORITO E, et al.Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection[J].Hepatology, 2006, 44 (2) :326-334.
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