AASLD 2011:HBV Treatment Induced HBsAg Seroconversion to Anti-HBs in 9 Asian-Ame

StephenW

HBV Treatment Induced HBsAg Seroconversion to Anti-HBs in 9 Asian-American Patients: Experience in a Community Clinic
H. Lee1; K. Hu1; S. Tonthat1
1. GI/Hepatology, U.C. Irvine, Irvine, CA, United States.


Background: Although HBeAg seroconversion to anti-HBe has been a standard treatment endpoint for HBeAg+ patients, patients who achieve this endpoint have a 20-40% relapse rate over a 5 year period. HBsAg seroconversion appears to be a more durable endpoint of HBV treatment than HBeAg seroconversion, but it is difficult to achieve. Several natural history cohorts of HBV patients have shown a low incidence of spontaneous HBsAg seroconversion, approximately 0.5-1.0% per year. Registration trials of HBeAg+ patients on tenofovir DF have shown 10.8% of patients achieve HBsAg loss and 7.7% of patients seroconvert to anti-HBs over 4 years. However, HBsAg loss was not seen in Asian patients or in HBeAg-negative patients.

Aim: To assess the probability and durability of HBsAg seroconversion in Asian-American patients treated with standard of care (SOC) nucleos(t)ide analogue oral agents in a community clinic.

Methods: A retrospective chart review of patients with CHB, who received nucleos(t)ide therapy from a single Irvine, CA clinic from 2008-2010.

Results: We identified nine Asian-American patients on treatment with nucleos(t)ide analogs who achieved HBsAg seroconversion. 4/9 (44%) were male, 8/9 (89%) were HBeAg negative at baseline, and the median age was 48 y.o. 4/9 patients were started on therapy by their primary physician, and their baseline viral load and ALT were not available. For the five patients with complete data, the median starting HBV DNA level was 69,392 IU/ml, and median ALT level was 53 U/L. 6/9 patients were treated with tenofovir (one of whom had lamivudine + TDF), 2 were treated with entecavir (ETV), and 1 was treated with adefovir (ADV). All nine patients achieved a normal ALT and undetectable HBV DNA on treatment. Treatment was discontinued in one patient when he achieved a HBsAb level over 50 mIU/ml. He was treated for 27 months with entecavir before achieving this endpoint. Ten months later, this patient was found to have a viral load of 13,737 IU/ml (79,949 copies/ml). His HBsAg was detectable, and he was started on tenofovir (TDF) at the time of this abstract submission.

Conclusions: Our experience shows it is possible for HBeAg negative Asian-American patients to seroconvert to anti-HBs while on oral CHB therapy. Using a quantitative HBsAb level of >50 mIU/ml as an endpoint to discontinue therapy was difficult to achieve, and did not prevent relapse in the one patient who achieved it, despite a persistently detectable HBsAb level. Further studies are needed in larger patient populations to determine the best endpoint for stopping oral CHB therapy, to maximize durable seroconversion and viral suppression.

StephenW

乙肝治疗乙肝表面抗原诱导抗- HBs血清转换9亚裔美国人的患者：在一个社区诊所的经验
H.李1; K.胡锦涛1 S. Tonthat 1
1。 GI /肝脏，U.C.尔湾，加利福尼亚州欧文，美国。


背景：虽然已HBeAg转阴抗- HBe +患者HBeAg的一个标准的治疗终点，实现这一目标端点的病人有20-40％的复发率超过5年的时间内。乙肝表面抗原血清学转换似乎是一个更持久的端点HBV比HBeAg血清转换的治疗，但它是难以实现的。乙肝患者的自然史的几个同伙，有一个自发的乙肝表面抗原血清转换的发生率较低，每年约0.5-1.0％。替诺福韦DF对HBeAg +患者的登记试验表明，10.8％的患者达到HBsAg消失和7.7％的患者seroconvert，超过4年的抗- HBs。然而，HBsAg消失不见在亚洲患者或HBeAg阴性患者。

目的：评估在亚洲和美国的病人标准护理（SOC）在社区诊所核苷（酸）IDE模拟口服药物治疗乙肝表面抗原血清转换的可能性和耐久性。

方法：慢性乙肝，谁收到从一个单一的加利福尼亚州欧文诊所从2008年至2010年的核苷（酸）IDE治疗患者进行回顾性图审查。

结果：我们确定了9个亚洲裔患者治疗核苷（酸）IDE类似物实现表面抗原血清学转换。 4 / 9（44％）为男性，8 / 9（89％）为HBeAg基线负，平均年龄为48岁4 / 9例患者在治疗开始他们的主治医生，和基线病毒载量和ALT不可用。对于资料完整的5例患者，中位数开始的HBV DNA水平是69,392 IU / ml的，ALT水平中位数为53 U / L。 6 / 9例患者（其中有拉米夫定+ TDF）与替诺福韦治疗，2例治疗与恩替卡韦（ETV），并与阿德福韦（ADV）治疗1。所有9例，取得了一个治疗ALT正常和乙肝病毒DNA检测不到。停止治疗一个病人，当他达到了一个抗- HBs水平超过50 MIU /毫升。他与恩替卡韦治疗27个月前实现这一目标的端点。 10个月后，这名病人被发现有13737 IU / ml的（79949拷贝/ ml）的病毒载量。他的乙肝表面抗原检测，并在本提交论文摘要时，他开始替诺福韦（TDF）。

结论：我们的经验表明，它有可能为负亚裔美国人的患者，seroconvert抗- HBs，同时对口腔的慢性乙型肝炎治疗HBeAg的。作为终点停止治疗的定量> 50 MIU / ml的抗- HBs水平是难以实现的，并没有阻止谁来实现它在一个病人的复发，尽管持续检测抗- HBs水平。需要进一步研究，在较大的患者人群，以确定最佳端点停止口服慢性乙型肝炎治疗，最大限度地实现持久的血清转换和病毒抑制。

MiddleAgeMan

Hi. StephenW:

I found out that the title is misleading:

HBV Treatment Induced HBsAg Seroconversion to Anti-HBs in 9 Asian-American Patients: Experience in a Community Clinic

Should the title be

HBV Treatment Induced HBsAg Seroconversion to Anti-HBs in 1 out of 9 Asian-American Patients: Experience in a Community Clinic

StephenW

MiddleAgeMan 发表于 2011-10-25 03:53
Hi. StephenW:

I found out that the title is misleading:

The title is not misleading. They did identify 9 patients who seroconverted to HbsAg negative.
All of them were on oral antiviral treatment.

I must admit this abstract cause me a lot of anxiety. They talked about one patient who stopped treatment when he achieved HBsAg -ve, AND HBsAb > 50 mIU/mL (10 mIU/mL is considered to be protective!). Yet this patient relapsed 10 months later, regaining HBsAg+ve and hbvdna.  Would really like to find out more.

There is an embargo on all the papers, abstracts, and posters from AASLD 2011. Let's hope someone will give us  more information after these are presented at the meeting.

MiddleAgeMan

Hi. StephenW:

You are right about the title. I was not reading carefully. However it is strange to me that the abstract does not mention the whole patient population.

Am I wrong again?

Thanks.

Dan

StephenW

回复 MiddleAgeMan 的帖子

You are not wrong. Yes, it did not say anything about the other 8: e.g. are they still on treatment?

I guess these questions can be asked when the abstract/poster is presented at the meeting. I get the feeling Conference organizers are limiting the words in abstracts/posters because there are so many.

2012痊愈

都英文甲流！verry good！

把握当下

社区诊所9名亚裔美国患者乙肝治疗表面抗原转阴经验

背景：虽然HBeAg阳性患者的治疗终点是达到HBeAg血清转换，但达到该终点的患者在5年之内有
20-40%复发。比起HBeAg血清转换，HBsAg血清转换似乎是更理想持久的治疗终点，但很难达到。一些乙肝患者自然病史报告表明自发HBsAg血清转换几率很低，约为每年0.5-1.0%。有记录的4年替诺临床试验表明，HBeAg阳患者有10.8%HBsAg转阴率，7.7%有了表面抗体。然而HBsAg转阴在亚裔和HBeAg阴性患者中未见。

目标：评估社区诊所亚裔美国乙肝患者使用口服核苷类药物进行标准化治疗的HBsAg血清转换比例和持续性。

方法：回溯2008-2010年在Irvine, CA诊所进行核苷肝药物治疗的乙肝患者病史。

结果：我们找到9名获得HBsAg转换、使用核苷类药物的亚裔美国患者。4/9 (44%)男性，初始基值：8/9 (89%)HBeAg阴性，平均年龄48。4/9在初级医生建议下开始治疗，患者病毒量和ALT基值未知；5名患者有完整数据， HBV DNA平均基值为69,392 IU/ml，ALT平均基值为53 U/L。6/9患者使用替诺福韦（其中1人使用拉米+替诺），2人使用恩替，1人使用阿德。全部9人治疗期间ALT正常，HBV DNA转阴。其中1人表面抗体超过50 mIU/ml时停药，取得该效果前使用了27个月恩替；10个月之后，病毒载量反弹到13,737 IU/ml (79,949 copies/ml)，HBsAg阳性，改用替诺治疗。

结论：我们的经验表明有HBeAg阴性亚裔美国患者在口服乙肝药物治疗期间获得表面抗体。表明抗体定量>50 mIU/ml作为停药终点很难达到，且即使如此仍有复发，表面抗原持续阳性。还需增加患者样本数量，对口服乙肝治疗停药标准进行进一步研究，增加血清转换持续性和病毒抑制作用。