HBsAg与Anti-HBs双阳性乙肝患者的临床特征及S区基因测序分析

Clinical characteristic and S region gene sequencing analysis in hepatitis B patients with coexistence of HBsAg and Anti-HBs

目的分析和讨论HBsAg和Anti-HBs双阳性HBV感染患者的临床特征及S区基因测序情况。方法收集HBsAg阳性患者乙肝五项及定量结果、肝功能和HBV DNA载量,记录其基本临床信息。根据Anti-HBs的阴阳性分组,并对两组结果的临床和病毒学特点进行分析。同时,17320例HBsAg阳性HBV感染患者中有994例进行了基因测序检测,对该994例患者的S区氨基酸突变、位点变异检出率和基因型进行统计分析。结果HBsAg和Anti-HBs双阳性率为4.36%(756/17320)。HBsAg+/Anti-HBs+组HBV相关性肝硬化(19.71%)显著高于HBsAg+/Anti-HBs-组(15.94%),而慢性乙型肝炎(62.04%)显著低于HBsAg+/Anti-HBs-组(67.06%)。同时,HBsAg+/Anti-HBs+组HBsAg-QN以及ALT均显著低于HBsAg+/Anti-HBs-组,HBeAg阳性率显著高于HBsAg+/Anti-HBs-组,HBV DNA则高于HBsAg+/Anti-HBs-组但差异无统计学意义。994例HBV感染者进行了基因测序检测,两组的C基因型(81.79%)最多,B基因型(17.40%)次之,D基因型(0.80%)最少。HBV感染患者C基因型的sP120Q/T/A/S位点检出率HBsAg+/Anti-HBs+组显著高于HBsAg+/Anti-HBs-组;无论B或C基因型或整体比较,HBV感染患者的sG145A/E/K/R位点检出率HBsAg+/Anti-HBs+组均显著高于HBsAg+/Anti-HBs-组,差异具有统计学意义。结论HBsAg和Anti-HBs双阳性HBV感染患者更易发展为肝硬化,且进行基因测序的乙肝患者以C2型为主。HBV感染患者的S区sP120Q/T/A/S和sG145A/E/K/R位点耐药变异是导致HBsAg和Anti-HBs双阳性的重要原因。

Objective In this article,we analyzed and discussed the clinical characteristics and S region gene sequencing of hepatitis B virus in HBsAg anti-HBs coexistent patients.Methods Data of 5 serologic markers of hepatitis B and quantitative result,liver function and HBV DNA load of HBsAg positive patients were collected,and their basic clinical information were recorded.According to the positive and negative result of Anti-HBs,the clinical and virological characteristics of these two groups were analyzed.At the same time,among 17320 patients with HBsAg positive HBV infection,994 cases were tested by gene sequencing.The S region amino acid mutation,site mutation detection rate and genotype of 994 HBV infected patients with gene sequencing were statistically analyzed.Results The positive rate of HBsAg and Anti-HBs was 4.36%(756/17320).HBV-related cirrhosis in HBsAg+/Anti-HBs+group(19.71%)was significantly higher than that in HBsAg+/Anti-HBs-group(15.94%),while chronic hepatitis B(62.04%)was significantly lower than that in HBsAg+/Anti-HBs-group(67.06%).At the same time,the positive rates of HBsAg-quantification(QN)and ALT in HBsAg+/Anti-HBs+group were significantly lower than those in HBsAg+/Anti-HBs-group,the positive rate of HBeAg was significantly higher than that in HBsAg+/Anti-HBs-group,and the HBV DNA was higher than that in HBsAg+/Anti-HBs-group,but the difference was no statistical significance.Gene sequencing was performed in 994 HBV patients.Genotype C(81.79%)had the highest proportion,genotype B(17.40%)was the second,and genotype D(0.80%)was the least in two groups.In genotype C HBV infected patients,the detection rate of sP120Q/T/A/S mutant in HBsAg+/Anti-HBs+group was significantly higher than that in HBsAg+/Anti-HBs-group.Meanwhile,regardless of genotype B or C or overall comparison,the detection rate of sG145A/E/K/R mutant of HBV infected patients in HBsAg+/Anti-HBs+group was significantly higher than that in HBsAg+/Anti-HBs-group,these differences were all statistically significant.Conclusions The hepatitis B patients with coexistence of HBsAg and Anti-HBs were more likely to develop cirrhosis,and the hepatitis B patients with HBV gene sequencing results were mainly type C2.The drug resistance variation of S-region sP120Q/T/A/S and sG145A/E/K/R mutants of patients with HBV infection is an important reason for the coexistence of HBsAg and Anti-HBS.