Analysis of S region gene mutation in patients with HBsAg+/HBsAb+ chronic hepatitis B
SUN Yu1* ZHANG Honghai1* CHEN Dexi2 WEI Feili2 GUO Xianghua2 SHI Ying2
1.Minimally Invasive Interventional Center of Oncology, Beijing You′an Hospital, Capital Medical University, Beijing 100069, China;
2.Beijing Institute of Liver Diseases, Beijing 100069, China
Abstract：Objective To study the S region gene mutation in patients with hepatitis B surface antigen (HBsAg) +/ hepatitis B surface antibody (HBsAb) + chronic hepatitis B (CHB). Methods From June 2012 to October 2017, 32 cases of CHB patients with double positive HBsAg and HBsAb in Beijing You′an Hospital, Capital Medical University (hereinafter referred to as “our hospital”) were selected as subjects (HBsAg+/HBsAb+ group),79 cases of CHB patients diagnosed with HBsAg+ and HBsAb- in our hospital in the same period were randomly selected as the control group (HBsAg+/HBsAb- group). The plasma viral DNA was isolated, the S region gene was amplified by PCR, and the mutation was analyzed by sequencing. Results All patients in the HBsAg+/HBsAb+ group had S-region mutation (100%), and the frequency was significantly higher than that in the HBsAg+/HBsAb- group (84.81%) (P ＜ 0.05). Moreover, the mutations were mostly concentrated in the subunits 1 and 3 of S region. The proportion of multiple site mutations in S region in HBsAg+/HBsAb+ group was significantly higher than that in HBsAg+/HBsAb- group (P ＜ 0.01). Conclusion The increased frequency of S region gene mutation and the presence of multiple mutations are closely related to the change of S antigen antibody in CHB patients, and the accumulation of this mutation indicates an adverse disease process.
孙玉1* 张洪海1* 陈德喜2 魏飞力2 郭向华2 石英2. HBsAg+/HBsAb+慢性乙型肝炎患者S区基因突变分析[J]. 中国医药导报, 2019, 16(5): 118-121.
SUN Yu1* ZHANG Honghai1* CHEN Dexi2 WEI Feili2 GUO Xianghua2 SHI Ying2. Analysis of S region gene mutation in patients with HBsAg+/HBsAb+ chronic hepatitis B. 中国医药导报, 2019, 16(5): 118-121.
[1] Hutin YJ，Bulterys M，Hirnschall GO. How far are we from viral hepatitis elimination service coverage targets? [J] J Int AIDS Soc，2018，21（Suppl 2）：e25050.
[2] Ott JJ，Stevens GA，Groeger J，et al. Global epidemiology of hepatitis B virus infection：new estimates of age-specific HBsAg seroprevalence and endemicity [J]. Vaccine，2012，30（12）：2212-2219.
[3] 贾继东，庄辉.携手推动中国慢性乙型肝炎治疗的可及性[J].肝脏，2016，21（4）：239-240.
[4] Gerlich WH. Medical virology of hepatitis B：how it began and where we are now [J]. Virol J，2013，10：239.
[5] Kohno H，Inoue T，Tsuda F，et al. Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B [J]. J Gen Virol，1996，77（Pt 8）：1825-1831.
[6] Mimms L. Hepatitis B virus escape mutants：“pushing the envelope”of chronic hepatitis B virus infection [J]. Hepatology，1995，21（3）：884-887.
[7] Ding F，Miao XL，Li YX，et al. Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs [J]. Braz J Infect Dis，2016，20（1）：1-7.
[8] Lee BS，Cho YK，Jeong SH，et al. Korean Hepatitis Epidemiology Study Group. Nationwide seroepidemiology of hepatitis B virus infection in South Korea in 2009 emphasizes the coexistence of HBsAg and anti-HBs [J]. J Med Virol，2013，85（8）：1327-1333.
[9] Liu K，Xie M，Lu X，et al. Mutations within the major hydrophilic region （MHR） of Hepatitis B virus from individuals with simultaneous HBsAg and anti-HBs in Guangzhou，Southern China [J]. J Med Virol. 2018，90（8）：1337-1342.
[10] Inoue J，Kondo Y，Wakui Y，et al. Reactivation of resolved hepatitis B virus infection with immune escape mutations after long-term corticosteroid therapy [J]. Clin J Gastroenterol，2016，9（2）：93-98.
[11] 中华医学会肝病分会.中华医学会感染病学分会.慢性乙型肝炎防治指南[J].临床肝胆病杂志，2011，27（1）：1-16.
[12] Cooreman MP，Leroux-Roels G，Paulij WP. Vaccine-and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen [J]. J Biomed Sci，2001，8（3）：237-247.
[13] Shizuma T，Hasegawa K，Ishikawa K，et al. Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus [J]. J Gastroenterol，2003，38（3）：244-253.
[14] Rodriguez-Frias F，Buti M，Jardi R，et al. Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B，chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation [J]. Liver，1999，19（3）：177-182.
[15] Mohebbi A，Lorestani N，Tahamtan A，et al. An Overview of Hepatitis B Virus Surface Antigen Secretion Inhibitors [J]. Front Microbiol，2018，9：662.
[16] Kalinina T1，Iwanski A，Will H，et al. Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R [J]. Hepatology，2003， 38（5）：1274-1281.
[17] 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.
[18] 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.
[19] Ding F，Yu HG，Li YX，et al. Sequence analysis of the HBV S protein in Chinese patients with coexisting HBsAg and anti-HBs antibodies [J]. J Med Virol，2015，87（12）：2067-2073.
2019, Vol. 16 
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