三个海外专家讨论一篇论文

StephenW

三个海外专家讨论一篇论文

Patrick Marcellin, MD

Norah Terrault, MD, MPH

Anna S. F. Lok, MD

论文是:

Telbivudine Use in Late Pregnancy in HBeAg-Positive Mothers Safely Reduces Perinatal HBV Transmission

HBeAg阳性母亲在妊娠晚期使用替比夫定, 安全降低母婴传播

Posting Date: November 04,2010

发布日期：2010年11月4日

Prospective, nonrandomized,case-controlled, open-label study

前瞻性，非随机，病例对照，开放性研究

Summary of Key Conclusions

主要结论

Telbivudine use in highlyviremic HBeAg-positive mothers during Weeks 20-32 of pregnancy reduces mother-to-child transmission of HBV

高病毒e抗原阳性的母亲在20-32周怀孕期间,使用替比夫定减少母亲对儿童的乙肝病毒传播

Telbivudine well tolerated inlate pregnancy with no short-term safety signals in telbivudine-treated mothers or their infants

在妊娠晚期替比夫定良好耐受性, 替比夫定治疗的母亲或他们的婴儿没有短期安全示意

No increase in pregnancy ordelivery complications

没有增加怀孕或分娩复杂枝节

No congenital deformities of adverse effects on infant development through 28 postpartum weeks offollow-up

产后续28周没有无先天性畸形, 无婴儿发育不良影响.

Findings support telbivudineuse in highly viremic HBeAg-positive mothers for prevention of perinatal transmission of HBV

研究结果支持在高病毒血症HBeAg阳性母亲使用替比夫定,预防乙肝病毒的母婴传播

Norah  Terrault, MD,MPH:
On the topic of preventing perinatal HBV transmission, Han and colleagues[27] reported the results of an important study adding to the slowly growing dataset on the use of antiviral treatment in HBV-infected women during late pregnancy to prevent perinatal transmission. This non randomized, prospective, multicenter study conducted inChina offered HBeAg-positive women with HBV DNA > 1 x 106copies/mL who were at Weeks 20-32 of gestation the choice between telbivudine600 mg/day (n = 94 women; n = 95 infants) or no antiviral therapy (n = 92 women; n = 92 infants) ([url=]CapsuleSummary[/url]).
关于防止母婴传播，韩(Han) 和同事们[27]报道一个重要的研究结果, 添加,缓慢增长,
关于HBV感染的妇女,在妊娠后期，抗病毒治疗, 以防止母婴传播, 的数据集。这种非随机(non-random)，前瞻性，多中心研究,在中国进行. 提供e抗原阳性与HBV DNA> 1× 106拷贝/毫升的妇女 ,在妊娠20-32周之间,选择替比夫定600毫克/天（N=94 妇女; N =95 婴儿）或不要抗病毒治疗（N= 92 妇女，N= 92 名婴儿）（胶囊摘要）。

Although offering study participants the choice between treatment groups introduces the potential for bias, most baseline characteristics including age, number of previous pregnancies, HBV DNA level,and ALT levels were at least statistically similar in both groups. The median HBV DNA level was 8.19 log10 copies/mL in the telbivudine group and7.96 log10 copies/mL in the control group (P = .134). Themedian ALT levels were within the normal range in both groups at 22.35 U/L and27.60 U/L, respectively (P = .528); approximately one third ofindividuals in both groups had ALT levels greater than the upper limit ofnormal. However, women who chose to receive telbivudine had a higher prevalenceof previous antiviral therapy (10.6%) relative to women who chose not toreceive therapy (0%; P = .002).
虽然允许, 参与研究者他们自行选择治疗组, 可以引入偏见潜力(potential for bias)，基线特征, 包括年龄，以前怀孕数次，HBV DNA 水平和ALT水平, 至少统计学上(statistically)两组相似。在替比夫定组,HBV DNA中位数水平为8.19 log10拷贝/毫升，对照在对照(control)组,7.96 log10拷贝/毫升，P=0.134）。两组的ALT水平的中位数(medium) 均在正常范围，分别为22.35 U / L 和27.60 U / L，(P=0.528）;在两组, 大约三分之一的妇女, ALT水平高于正常上限。然而，选择了接受替比夫定抗病毒治疗的妇女, 他们已接受过治疗率较高（10.6％），相对于选择不接受治疗妇女 (0％，P=0.002）。

This study differs from similar trials investigating third-trimester antiviral therapy[22,28,29] in that he investigators permitted treatment initiation earlier, at 20 weeks of gestation during the second trimester. Participants receiving telbivudine continued treatment for 4 weeks postpartum. Women who had indications or reason to consider longer treatment continued telbivudine therapy to postpartum Week28. All infants received HBIG and HBV vaccine within 24 hours after delivery and additional HBV vaccine at 1 and 6 months after delivery.

这项研究不同于[22,28,29]类似调查从第三孕期 (third-trimester) 进行抗病毒治疗的试验 . 这项研究允许在妊娠20周, 孕中期(second trimester), 开始治疗. 接受替比夫定治疗者会继续治疗到产后4周。妇女,认为有指示或理由,再继续替比夫定治疗到产后28周。所有婴儿在产后24小时收到HBIG和乙肝疫苗, 和1和6 个月后的额外乙肝疫苗。

The investigators compared HBsAg positivity at 28 weeks of age among infants in the treated and untreated groups by both intent-to-treat and per protocol analyses.

研究人员比较婴儿在28周龄,乙肝表面抗原阳性, 在处理和未经处理组 ,意向處理分析(intent-to-treat)和协议(per ptotocol))分析。

[在流行病學方面, 意向處理分析 (intention-to-treatanalysis; ITT analysis)是分析根據最初的治療意向，不是在治療最終被執行。它根據假定，和在真正的生活中，患者全部有時不接受優選的治療，即使那是最初的意

StephenW

Anna S. F. Lok, MD: According to the intent-to-treat analysis,2.1% of infants in the telbivudine group vs 13.0% of infants in the untreatedgroup were HBsAg positive 28 weeks after birth (P = .004). In thesensitivity (per protocol) analysis, the rates of HBsAg positivity were 0% vs8.7%, respectively (P = .003).

安娜S.F. 乐，MD：
根据, 意向處理分析，在替比夫定组 2.1％婴儿 和在治疗组13.0％婴儿, 是HBsAg阳性的,在出生后28周（P =0.004）。
在灵敏度(sensitivity)（per protocol）的分析，乙肝表面抗原阳性率分别为 0％ 对
8.7％，（P=0.003）。

The proportion of infants who tested positivefor HBsAg at the time of delivery was much higher in both groups: 6.3% withtelbivudine vs 30.4% without treatment. Many other studies examining perinatalHBV transmission have similarly reported that the rate of HBsAg detection ismuch higher in cord blood at the time of birth relative to venous blood a fewmonths after birth. My interpretation is that cord blood may be contaminatedwith maternal blood; the presenter’s interpretation was that the higher ratesat birth reflected infants who acquired intrauterine HBV infection that wassubsequently eradicated by HBIG and vaccine administration.
婴儿在分娩时测试, HBsAg的阳性比例是高得多.两组：替比夫定6.3％，相对没有接受治疗30.4％。许多研究母婴传播等研究,同样报告说，乙肝表面抗原检出率,在出生时脐带(cord)的血,要高得多于出生几个月后静脉的血液。我的理解是，脐带血可能与母体血液污染; 研究者的解释是，出生婴儿的高率反映乙肝病毒宫内感染,后来被HBIG 和
疫苗管理获得根除。

Norah Terrault, MD, MPH:This study also reported reassuring safety outcomesshowing similar pregnancy duration and similar risk of abnormal pregnancy,cesarean section, and postpartum hemorrhage with telbivudine vs no treatment.In addition, there were no early discontinuations as a result of adverse eventsin mothers receiving telbivudine, and no congenital deformities occurred ininfants from either group.

这项研究还报道令人欣慰的安全性结果, 显示类似的怀孕期,类似异常妊娠的风险，剖宫产(caesarean) 和产后出血的风险 , 在替比夫定治疗组对与没有任何治疗组。此外，还有,母亲在接受替比夫定治疗, 没有不良事件导致早期停药，并没有发生婴儿先天畸形。

Another very useful finding from this studywas that women receiving telbivudine experienced a lower rate of postpartum ALTflare relative to women who did not receive antiviral therapy (7.45% vs 18.48%,respectively; P = .025). Among the subset of women who discontinuedtelbivudine at postpartum Week 4 (n = 55), 12.73% experienced a subsequentpostpartum ALT flare. This result does not suggest that discontinuingtelbivudine put women at an increased risk for ALT flares.

这项研究的另一个发现是非常有用的.女性接受替比夫定经历了较低产后ALT突然上升(flare) 相对于女性不接受抗病毒治疗（分别为7.45％和18.48％，P=0.025）。其中产后第4周, 停止替比夫定的妇女组（N=55），12.73％，其后经历了产后ALT突然上升(flare)。这个结果并不意味着停止替比夫定增加妇女ALT突然上升(flare)的风险。

Anna S. F. Lok, MD:
However, study follow-up continued only topostpartum Week 28, therefore the incidence of ALT flare in women who stoppedtelbivudine treatment at postpartum Week 28 is not known.

然而，研究续持产后第28周，因此对在产后第28周,停止使用替比夫定治疗的妇女,不知道他们有没有ALT突然上升(flare)的发生。

Patrick Marcellin, MD: Although the study is not perfect, itincludes a relatively large number of pregnant women with high HBV DNA levelsand provides results that are consistent with other studies suggesting thatantiviral treatment during late pregnancy should be considered in pregnantHBeAg-positive women with high HBV DNA levels.[22,28,29]
尽管这项研究是不完美的，它包括了比较多HBV DNA水平高的孕妇，提供了与其他研究如一(consistent)的结果，表明在妊娠晚期, 有高HBV DNA水平的e抗原阳性怀孕的妇女,应考虑接受抗病毒治疗[22,28,29]

Norah Terrault, MD, MPH: I agree with that assessment. In my opinion,this study makes an important contribution to the literature on this topic.
我同意这一评估。在我看来，这项研究, 在关于这一主题的文学,作出了重要的贡献。

It would be very helpful to the treatingcommunity if the study investigators were to perform an additional analysis totry to define an appropriate maternal HBV DNA cutoff level above whichantiviral therapy offers the greatest benefit in reducing perinataltransmission. The inclusion criteria required an HBV DNA level > 1 x 106copies/mL, which is somewhat lower than previous studies.[22,28]Other studies have generally focused on women with HBV DNA levels ofapproximately 107-109 copies/mL, and most physicians usea cutoff level of 108 copies/mL or approximately 2 x 107IU/mL to define which pregnant women should be offered antiviral therapy in thethird trimester. A recent study from Australia found that among 138 infantsborn to HBsAg-positive women, the only cases of transmission were fromHBeAg-positive mothers who had HBV DNA levels > 108 copies/mL.[21]It would be useful to examine similardata on maternal HBV DNA levels in cases of transmission from the current studyto help refine recommendations. It is possible that treatment could berestricted to HBeAg-positive pregnant women who have high HBV DNA levels, buthaving a specific HBV DNA cutoff level would lead to more consistency amongpractitioners.

这将是非常有帮助治疗医生群体，如果调查人员执行额外的分析，试图确定一个合适的孕产妇HBV DNA截止(cut-off)水平, 高于这一水平, 抗病毒治疗该提供了减少母婴传播的最大好处。入选这项临床试验, 标准要求HBV DNA水平> 1× 106拷贝/毫升，这是比以往的研究有所降低[22,28]. 其他研究一般集中在乙肝病毒DNA约1x107-109 拷贝/毫升程度的妇女，和大多数医生使用的1x108拷贝/毫升或约2 ×107 IU/mL 截止(cut-off) ,定义哪些孕妇应提供在孕晚期抗病毒治疗。来自澳大利亚最近的一项研究发现
，在乙肝表面抗原阳性的妇女出生的138婴儿，传播的唯一案件，来自一个e抗原阳性的母亲HBV DNA水平> 108拷贝/ ml者[21] . 这将是有益的,从目前的研究,探讨传播产妇
HBV DNA的水平的类似的数据，以帮助改进建议。这可能是治疗可以限制在HBeAg阳性具有较高的HBV DNA水平的孕妇，但如果有一个具体的HBV DNA截止(cut-off)水平 , 将导致更多从业人员之间的一致性。

StephenW

从这个讨论中，我学到三件事情：

1。从婴儿的脐带血测试HBsAg的结果是不可靠的;
2。医生很谨慎，采用一个医疗治疗方法前, 他们要看到许多临床观察与许多类似的
结果;
3。海外医生认真关注从中国到医学研究.

From this discussion, I learn 3 things:

1. Test result for HbSag from a baby's cord blood is not reliable;
2. Doctors are very cautious, they like to see results from many clinical observations before adopting a medical treatment;
3. Overseas doctors are paying serious attentions to medical studies from China.

渠水欢歌

谢楼主提供的资料。