分析隐匿性乙型肝炎病毒感染（OBI）患者的HBV preS/S基因突变，探讨其对严重肝功能损伤进展的影响。

收集于广州市番禺区市桥医院体检、门诊及住院的HBsAg阴性患者共689例，对其血清样本进行荧光定量PCR扩增，共检出76例OBI患者作为研究组，另外选取HBsAg阳性患者87例作为对照组。对两组患者血清样本进行preS/S区基因测序，统计HBcAb、HBeAb、HBeAg、HBcAb/HBsAb阳性检出率，比较两组患者HBV DNA载量和preS/S区各基因突变频率。

研究组76例OBI患者标本中HBcAb、HBeAb、HBeAg、HBcAb/HBsAb阳性者分别为14例（18.42%）、9例（11.84%）、27例（35.53%）和26例（34.21%）；preS/S区检出基因型B型患者11例（14.5%），C型患者65例（85.5%）。对照组标本S区检出B型患者19例（21.8%），C型患者68例（78.2%），两组患者均未检出D型HBV，基因型差异无统计学意义（χ² = 1.794、P = 0.180）。研究组患者HBV DNA载量为76～1 989 IU/ml（中位数为186.6 IU/ml），显著低于对照组[573.7（108～5 689）IU/ml]，差异有统计学意义（Z = 25.775、P < 0.001）。研究组OBI伴严重肝损伤（ALT ≥ 120 U/L）患者HBV DNA载量为76～1 989 IU/ml（中位数为193 IU/ml），显著高于该组中无严重肝功能损伤者[178.6（77～1 325）IU/ml]，差异有统计学意义（Z = 14.638、P < 0.001），但显著低于对照组伴严重肝功能功能损伤患者[623.7（217～5 689）IU/ml]，差异有统计学意义（Z = 21.396、P < 0.001）。研究组患者preS/S区G185R、T118R/K/A/M、L175S、I126s及preS缺失突变频率均显著高于对照组（P均< 0.05）；研究组OBI伴严重肝功能损伤患者中I126S突变频率稍低于该组中无严重肝功能损伤患者，但差异无统计学意义（χ² = 0.508、P = 0.476）；G185R、T118R/K/A/M、L175S及preS缺失则显著高于该组中无严重肝功能损伤患者（P均< 0.05）。研究组OBI伴严重肝功能损伤患者的I126s稍高于对照组伴严重肝功能损伤者，但差异无统计学意义（χ² = 3.287、P = 0.070）；而G185R、T118R/K/A/M、L175S及preS缺失突变频率则显著高于对照组中伴严重肝功能损伤患者（P均< 0.05）。

OBI患者中以HBeAg、HBcAb/HBsAb阳性检出者居多，突变基因型与HBsAg阳性基本一致。但OBI患者与HBsAg阳性患者HBV DNA载量以及基因突变存在较大差异，G185R、T118R/K/A/M、L175S及preS缺失突变可能是OBI患者发生严重肝功能损伤的重要检测指标。

To investigate the mutation of HBV preS/S gene in patients with occult hepatitis B virus (OBI) infection, and to explore its effect on the progress of severe liver function injury.

Total of 689 patients with negative HBsAg were collected from Shiqiao Hospital of Panyu District, Guangzhou. The serum samples were detected by fluorescence quantitative PCR amplification. Among the 689 patients, 76 patients with OBI were selected as research group, while 87 patients with HBsAg positive were selected as control group. The preS/S gene of HBV was sequenced of patients in both groups. The positive rates of HBcAb, HBeAb, HBeAg and HBcAb/HBsAb were calculated, respectively. The load of HBV DNA and gene mutation frequency in preS/S region between the two groups were compared, respectively.

Total of HBsAg negative serum samples from 76 cases with OBI with OBI were detected, among which, 14 samples (18.42%), 9 samples (11.84%), 27 samples (35.53%) and 26 samples (34.21%) were positive for HBcAb, HBeAb, HBeAg and HBcAb/HBsAb, respectively. There were 11 cases (14.5%) detected with HBV genotype B and 65 cases (85.5%) with genotype C in preS/S region; but no genotype D of HBV was detected in both groups, without significant difference in genotypes between the two groups (χ² = 1.794, P = 0.180). The load of HBV DNA in research group was 76-1 989 IU/ml (the median was 186.6 IU/ml), significantly lower than that of the control group [573.7 (108-5 689) IU/ml], with significant difference (Z = 25.775, P < 0.001). HBV DNA load of patients with OBI and severe liver function injury in research group was 76-1 989 IU/ml (median was 193 IU/ml), significantly higher than that of those patients without severe liver function injury in this group [178.6 (77-1 325) IU/ml], with significant difference (Z = 14.638, P < 0.001), however, it was significantly lower than that of control group with severe liver function injury [623.7 (217-5 689) IU/ml], with significant difference (Z = 21.396, P < 0.001). The frequencies of G185R, T118R/K/A/M, L175S, I126s and preS deletion mutations in preS/S region of patients in research group were significantly higher than those of the control group (all P < 0.05). The mutation frequency of I126s in patients with OBI and severe liver function injury was slightly lower than those of the cases without severe liver function injury in research group, but without significant difference (χ² = 0.508, P = 0.476). The deletion of L175S and preS in G185R, T118R/K/A/M and L175S were significantly higher than those of patients without severe liver function injury (all P < 0.05). The I126S of patients with severe liver function injury in research group were slightly higher than those of the control group, but without significant difference (χ² = 3.287, P = 0.070); but the frequencies of G185R, T118R/K/A/M, L175S and preS were significantly higher than those of cases with severe liver function injury in control group (all P < 0.05).

HBeAg and HBcAb/HBsAb positive dection were the most among patients with OBI, and the mutant genotype was basically consistent with the positive rate of HBsAg. However, the difference of HBV DNA load and gene mutation between patients with OBI and patients with HBsAg positive was significant. The deletion of G185R, T118R/K/A/M, L175S and preS may be important detection indexes for patients with OBI and severe liver function injury.