Tseng T-C, Liu C-J, Chen C-L, Yang W-T, Yang H-C, Su T-H, Wang C-C, Kuo S F-T, Liu C-H, Chen P-J, Chen D-S, Kao J-H
Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
Aliment Pharmacol Ther. 2015 May;41(10):949-60. doi: 10.1111/apt.13170. Epub 2015 Mar 23.
Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss.
We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers.
The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers.
Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.
乙肝表面抗原（HBsAg）清除表明乙肝病毒（HBV）感染得到临床控制。然而，关于病毒基因组变异对HBsAg清除的影响知之甚少。
我们在2121例HBeAg阴性患者中探索了病毒基因组因素与HBsAg清除之间的关联。对HBV DNA≥200 IU/mL的患者（N = 1693）测定HBV前核心终止密码子（1896）和基本核心启动子（BCP）（1762/1764）序列。在3445例HBsAg携带者的整个队列中进一步验证了HBV基因型对HBsAg清除的影响。
2121例HBeAg阴性患者中，HBsAg清除的累积终生（28 - 75岁）发生率为50.4%。我们发现C基因型与HBsAg清除相关，而前核心终止密码子或BCP突变体则不然。与B基因型患者相比，C基因型患者HBsAg清除的终生几率更高，风险比为1.8（95%置信区间：1.4 - 2.4）。多变量分析显示，男性、ALT水平升高、血清HBV DNA和HBsAg水平较低以及C基因型感染独立地与HBsAg清除几率较高相关。然后我们进行了敏感性分析，重新纳入了HBeAg阳性、肝硬化和有治疗史的患者，并在3445例HBsAg携带者中证实了我们结果的稳健性。
与B基因型相比，C基因型感染与亚洲HBV携带者HBsAg清除的终生几率较高相关。
