DDW2012: (HBsAg) Seroclearance Rate in a Multicenter US

StephenW

Hepatitis B Surface Antigen (HBsAg) Seroclearance Rate in a Multicenter U.S. Cohort Study Mo1902
Long H. Nguyen1, 2, Pelu Tran1, Kevin T. Chaung2, Vincent G. Nguyen2, Lily H. Kim3, Huy N. Trinh2, 4, Jiayi Li5, Jian Q. Zhang6, Huy A. Nguyen4, Walid Ayoub7, Aijaz Ahmed7, Mindie H. Nguyen7                                         
Affiliation
1School of Medicine, Stanford University, Stanford, CA; 2Pacific Health Foundation, San Jose, CA; 3Stanford University, Stanford, CA; 4San Jose Gastroenterology, San Jose, CA; 5Department of Gastroenterology, Palo Alto Medical Foundation, Mountain View, CA; 6Chinese Hospital, San Francisco, CA; 7Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA
Abstract:
PURPOSE: The spontaneous loss of HBsAg is thought to be a rare occurrence. Persistent HBsAg seropositivity is an important risk factor for advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC), and there have been few large cohort studies of U.S. patients. HBsAg seroclearance is also a rare occurrence in patients receiving antiviral therapy, though this is generally thought of as one of the most durable and desired treatment endpoints.  Our objective is to determine the annual incidence rate of HBsAg seroclearance and which clinical or laboratory characteristics predict for achieving HBsAg seroclearance.
METHODS: Using ICD-9 electronic query and chart review, 1621 patients from two community GI clinics, three community primary care clinics, one community multispecialty medical center, and one university medical center were retrospectively enrolled from 2001-2008. HBsAg seroclearance was determined by documented loss of HBsAg. Persistent HBsAg was verified directly with HBsAg serology or by proxy with positive HBeAg results or detectable HBV DNA levels.
RESULTS: HBsAg seroclearance occurred in 19 patients over the course of 4895 person-years (0.39% annual seroclearance rate, 1.2% overall). Median follow-up was 32 months and did not differ significantly between those who cleared HBsAg and those who did not. Compared to those who maintained HBsAg positivity, patients who achieved HBsAg seroclearance were older (mean 49±10 years vs. 43±13, p=0.04); however, the two groups of patients did not differ significantly on the following: proportion of males, BMI, history of treatment before or during follow-up, family history of viral hepatitis/HCC/cirrhosis, baseline HBeAg status, ALT, AFP, or HBV DNA level.
Annual incidence of HBsAg seroclearance differed significantly by age (0.28% for age ≤50 years vs. 0.73% for >50, p=0.02) and trended towards significance for baseline HBV DNA levels (0.29% for >10,000 IU/mL vs. 0.62% for ≤10,000 IU/mL, p=0.09) (Figure 1). HBsAg seroclearance rates did not differ significantly by sex, baseline HBeAg status, or by treatment history.
On multivariate Cox modeling also inclusive of sex, treatment history, and HBeAg status, older age was a significant predictor for HBsAg seroclearance (HR: 1.04, 95% CI: 1.00-1.07; p=0.03) and baseline HBV DNA≤10,000 IU/mL also trended towards significance (HR: 2.3, 95% CI: 0.86-6.2; p=0.09).
CONCLUSION:
HBsAg seroclearance rates may be lower than previously described, with or without treatment with oral antiviral agents. Increasing age was an independent predictor for seroclearance and low baseline HBV DNA revealed a trend towards significance. Further studies are needed to characterize the natural history of HBsAg seroclearance in U.S. patients who are treatment-naïve and treatment-experienced and in various age groups.

Disclosure(s):
Huy N. Trinh - Advisory Committees or Review Panels: Bristol-Myers Squibb, Bristol-Myers Squibb, Gilead Sciences Inc; Grant/Research Support: Gilead Sciences; Stock Shareholder: Gilead Sciences, Bristol-Myers Squibb
Huy A. Nguyen - Speaking and Teaching: Gilead Sciences Inc
Aijaz Ahmed - Advisory Committees or Review Panels: Salix Pharmaceuticals, Inc., Schering-Plough Corp., Vertex Pharmaceuticals , Three Rivers Pharmaceuticals, LLC; Grant/Research Support: Gilead Sciences Inc, Romark Laboratories, L.C.; Speaking and Teaching: Bristol-Myers Squibb Co. , Gilead Sciences Inc, Hoffman-LaRoche
Mindie H. Nguyen - Advisory Committees or Review Panels: Salix Pharmaceuticals, Schering-Plough, Schering-Plough, Vertex Pharmaceuticals , Three Rivers Pharmaceuticals, LLC; Grant/Research Support: Gilead Sciences, Romark Laboratories; Speaking and Teaching: Bristol-Myers Squibb, Gilead Sciences, Hoffman-LaRoche
The following people have nothing to disclose: Long H. Nguyen, Pelu Tran, Kevin T. Chaung, Vincent G. Nguyen, Lily H. Kim, Jiayi Li, Jian Q. Zhang, Walid Ayoub


                                                                           

StephenW

乙肝表面抗原（HBsAg）在美国一项多中心队列研究廓清率
Mo1902
长H. Nguyen1，2，Pelu Tran1，凯文吨Chaung2，文森特G。Nguyen2，百合H. Kim3，伊北Trinh2，4，嘉义LI5，健问Zhang6，伊答Nguyen4，Ayoub7瓦利德，Aijaz Ahmed7，Mindie H.的Nguyen7


加利福尼亚斯坦福大学，斯坦福大学，加利福尼亚州圣何塞，2Pacific健康基金会，大学3Stanford，斯坦福大学，加州圣何塞消化，加利福尼亚州圣何塞，4San;消化科5Department，山景，加州帕洛阿尔托医学基金会，医学，1School;胃肠病学和肝病7Division 6Chinese医院，旧金山，加州斯坦福大学医学中心，帕洛阿尔托，加利福尼亚

摘要：

目的：乙肝表面抗原的自燃损失被认为是一种罕见的发生。持久性乙肝表面抗原血清学阳性是一个先进的肝病，包括肝硬化和肝细胞癌（HCC）的重要危险因素，已经有一些美国患者的大型队列研究。乙肝表面抗原血清廓清也是罕见的发生在接受抗病毒药物治疗的患者，虽然这是普遍认为是最持久的和理想的治疗终点之一。我们的目标是确定的HBsAg廓清和临床或实验室的特点，为实现表面抗原血清廓清预测的年发病率。
方法：采用ICD-9电子查询和图审查，1621患者从两个社区胃肠诊所，3个社区初级保健诊所，一个社区multispecialty医疗中心，一所大学医疗中心进行回顾从2001-2008年就读。乙肝表面抗原血清廓清记录HBsAg消失。直接验证了持久的HBsAg与HBsAg血清学或代理与HBeAg阳性结果或检测HBV DNA水平。
结果：超过4895人，年（每年0.39％的廓清率，1.2％的整体）的过程中发生的19例乙肝表面抗原血清廓清。中位随访32个月，并没有那些清除乙肝表面抗原和那些没有显着差异。相比，维护乙肝表面抗原阳性，患者实现表面抗原血清廓清那些年龄较大（平均49±10岁与43±13，P = 0.04）;然而，两组患者没有不同以下明显的男性比例，体重指数，治疗前，肝炎/肝癌/肝硬化，基线HBeAg状态，血清ALT，法新社，或HBV DNA水平的家族病史或在后续的历史。
乙肝表面抗原血清廓清的年发病率显着不同年龄（0.28％为年龄≤50岁与0.73％> 50，P = 0.02）和对基线HBV DNA水平的重要意义（0.29> 10,000国际单位/毫升和0.62％的趋势％为≤10,000 IU /毫升，P = 0.09）（图1）。 HBsAg的廓清率没有显着差异，性别，基线HBeAg状态，或治疗史。
多元Cox模型也包容性，治疗的历史，和HBeAg状态，年龄为乙肝表面抗原血清廓清的显着预测因子（HR：1.04，95％CI为1.00-1.07，P = 0.03）和基线HBV DNA≤10,000 IU /毫升也趋于走向意义（HR：2.3，95％CI：0.86-6.2; P = 0.09）。
结论：
乙肝表面抗原血清廓清率可能低于先前所描述的，或不使用口服抗病毒药物治疗。随着年龄增长廓清和低基线HBV DNA的独立预测显示，对意义的趋势。还需要进一步研究的特点，在美国病人谁是天真的治疗和治疗经验，并在各年龄组乙肝表面抗原血清廓清的自然历史。

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学习了额。谢谢。。