Abstract:Objective To analyze the correlation between the mutation of S protein sequence of hepatitis B virus (HBV) and the coexistence of HBsAg and anti-HBs in patients with chronic hepatitis B (CHB). Methods Thirty-three CHB patients with coexisting HBsAg and anti-HBs were randomly selected as the experimental group, and 33 CHB patients with HBsAg positive but anti-HBs negative as the control group. The S gene of HBV was amplified and sequenced. Results HBV in the two groups was B or C genotype, without other genotypes. No statistically significant differences were observed in age, gender, HBV genotype and serum HBV DNA level between the two groups (all P>0.05). The amino acid mutation rates in the N-terminal (2.61% vs. 1.21%), major hydrophilic region (1.69% vs. 0.48%), especially "α" determinant (3.23% vs. 0.63%) of S protein were significantly higher in the experimental group than in the control group (all P<0.01), but no statistically significant difference was found in the amino acid mutation rate in the C-terminal of S protein (1.75% vs. 1.22%, P>0.05). The most frequent amino acid mutation in the experimental group was located at position 126 of S protein. There were no statistically significant differences in the deletion or insertion mutations between the two groups (P>0.05). Conclusions The amino acid mutations, especially those in the "α" determinant, in the patients with CHB may be associated with the coexistence of HBsAg and anti-HBs.
申春梅, 唐思叶, 王妹芳, 贺乐奇. HBsAg与anti-HBs共阳性慢性乙肝患者病毒S蛋白序列分析[J]. 实用预防医学, 2018, 25(12): 1458-1461.
SHEN Chun-mei, TANG Si-ye, WANG Mei-fang, HE Le-qi. Sequence of S protein in chronic hepatitis B patients with coexisting HBsAg and anti-HBs. , 2018, 25(12): 1458-1461.
[1] 中华医学会肝病学分会. 慢性乙型肝炎防治指南[J].中华肝脏病杂志,2015,23(12):321-340. [2] Huang X, Qin Y, Zhang P, et al. PreS deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis-B surface antigen and anti-HBs antibodies[J]. J Med Virol, 2010, 82(1):23-31. [3] Sunbul M. Hepatitis B virus genotypes: global distribution and clinical importance[J].World J Gastroenterol, 2014,20(18):5427-5434. [4] Yano Y, Azuma T, Hayashi Y. Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics[J].World J Hepatol,2015,7(3):583-592. [5] Park GC, Hwang S, Ahn CS, et al. Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy[J].Transplant Oroc, 2013,45(8):3047-3051. [6] Kim KH, Chang HY, Park JY, et al. Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers[J]. Clin Mol Hepatol,2014,20(3):251-260. [7] Pollicino T, Cacciola L, Saffioti F, et al. Hepatitis B virus PreS/S gene variant: pathobiology and clinical implications[J]. J Hepatol, 2014,61(2):408-417. [8] Suppiah J, Mohd Zain R, Bahari N, et al. S gene mutants occurrence among hepatitis B carriers in Malaysia[J]. Hepat Mon, 2014,14(12):e22565. [9] Liu Y, Zhang L, Zhou JY, et al. Clinical and virological characteristics of chronic hepatitis B patients with coexistence of HBsAg and anti-HBs [J]. PLoS One,2016,11(1):e0146980. [10] Huang CH, Yuan Q, Chen PJ, et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors[J].J Hepatol,2012,57(4):720-729. [11] 高春芳.HBV S区基因变异与HBsAg检测[J].中华检验医学杂志,2010,33(6):574-576. [12] Wang L, Liu H, Ning X, et al. Sequence analysis of the S gene region in HBV DNA from patients positive for both HBsAg and HbsAb tests[J]. Hepatol Res,2010,40(12):1212-1218. [13] Sticchi L,Caligiuri P,Cacciani R,et al.Epidemiology of HBV S-gene mutants in the Liguria Region,Italy: implications for surveillance and detection of new escape variants[J].Hum Vaccin Immunother,2013,9(3):568-571. [14] Seo SI, Choi HS, Choi BY, et al. Coexistence of hepatitis B surface antigen and antibody to hepatitis B surface may increase the risk of hepatocellular carcinoma in chronic hepatitis B virus infection: a retrospective cohort study[J]. J Med Virol,2014,86(1):124-130.