EASL 2013：亚洲患者更好地应对干扰素？

StephenW

EASL 2013: Do Asian Patients Respond Better to Pegylated Interferon for Hepatitis B?

   

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    Category: HBV Treatment   
    Published on Wednesday, 08 May 2013 00:00
    Written by Liz Highleyman



Some Asian people with chronic hepatitis B treated with pegylated interferon may experience better outcomes on certain measures than Caucasians, though overall response rates are similar, according to a comparative analysis presented at the EASL International Liver Congress(EASL 2013) last month in Amsterdam. The study also showed that early hepatitis B surface antigen (HBsAg) decline is a predictor of treatment response in some patients.

Nucleoside/nucleotide analog antiviral drugs such as lamivudine (3TC or Epivir), entecavir (Baraclude), and tenofovir (Viread) are the mainstay of treatment for chronic hepatitis B virus (HBV) infection. Pegylated interferon is recommended in international guidelines, but is used less often due to cost and side effects. While antivirals are effective at suppressing viral replication, interferon may increase the likelihood of serological responses involving HBV antigen loss and antibody seroconversion.

Patrick Marcellin from University Paris-Diderot presented findings from S-Collate, a prospective multinational study of a "real-life" cohort of people with chronic hepatitis B. The primary aim of the study was to evaluate on-treatment predictors of HBsAg clearance in routine clinical practice.

Previous studies have shown that a 10% or greater decline in HBsAg by week 24 of treatment was associated with sustained immune control among hepatitis B "e" antigen (HBeAg) negative patients, as was a 24-week HBsAg level below 1,500 IU/mL among HBeAg positive patients.

This analysis also looked at treatment outcomes according to Asian versus Caucasian race/ethnicity. Hepatitis B is endemic throughout much of Asia, with many people infected early in life through mother-to-child transmission. The meaning of "Asian" and "Caucasian" generated some discussion among attendees, who noted that people from the Indian subcontinent may be geographically Asian but anthropologically Caucasian; for the most part the study appeared to compare East Asian vs white patients.

The study included 592 HBeAg positive chronic hepatitis C patients (455 Asian and 137 Caucasian) and 641 HBeAg negative patients (224 Asian and 417 Caucasian). About 70% overall were men. The mean age was a bit younger in the HBeAg positive compared with the HBeAg negative group (about 31 vs 38 years). Duration of infection was longer for Asians than Caucasians (about 16 vs 12 years) and perinatal acquisition was more common (about 80% vs 30%). Asians also had higher ALT liver enzyme levels (183 vs 142 IU/L among HBeAg positives, 148 vs 101 IU/L among HBeAg negatives).

Participants were followed for 24 weeks before starting treatment with 180 mcg/week pegylated interferonalfa-2a (Pegasys) monotherapy for 48 weeks. Follow-up will continue through 3 years post-treatment; Marcellin reported 6 month post-treatment findings.

Results

    Looking at HBeAg positive patients, overall response rates at 6 months post-treatment were "similar for all endpoints" between Asians and Caucasians.
    Half in both groups reached HBV DNA levels < 2000 IU/mL, while 17% vs 27% fell to < 80 IU/mL (approaching statistical significance).
    HBV DNA < 2000 IU/mL plus ALT normalization was observed in 41% and 37%, respectively, while 20% and 28% achieved low viral load plus HBeAg loss.
    However, only 5% and 6%, respectively, achieved HBsAg loss, while 13% and 9% reached HBsAg levels < 100 IU/mL.
    Despite these similarities, Asians experienced a significantly greater decline in HBsAg from baseline compared with Caucasians, 1.35 vs 0.33 log, respectively.
    39% of patients with HBsAg levels <1500 IU/mL at treatment week 12 achieved both HBeAg loss and low HBV DNA, compared with 14% of those with 1500-20,000 IU/mL and 8% of those with > 20,000 IU/mL.
    Turning to HBeAg negative participants, Asians were significantly more likely than Caucasians to achieve HBV DNA below 2000 IU/mL either alone (65% vs 53%) or in conjunction with ALT normalization (57% vs 37%).
    However, 6 month post-treatment response rates were statistically similar with regard to HBV DNA < 80 IU/mL (32% vs 23%), HBsAg loss (8% vs 4%), and HBsAg < 100 IU/mL (18% vs 13%).
    In contrast with the HBeAg positive patients, HBeAg negative Asians and Caucasians had the same declines in HBsAg from baseline, 0.54 and 0.55 log, respectively.
    Treatment safety and tolerability did not differ between Asian and Caucasian patients.
    Rates of overall side effects and serious adverse events were similar, and 5% and 4%, respectively, discontinued treatment due to adverse events.

"In a 'real-life' setting, response rates to [pegylated interferon alfa-2a] were not different between Asia and Caucasian patients with chronic hepatitis B," the researchers concluded, although they noted that more HBeAg negative Asian patients achieved both low HBV DNA and ALT normalization.

"Early on-treatment HBsAg decline showed utility as a predictor of response 6 months post-treatment in HBeAg-positive Asian patients," they added.

This study conflicts with the common belief that Asian hepatitis B patients are "harder-to-treat." "I think response to interferon in Asians is similar to -- and maybe even better than -- [that of] Caucasians," Marcellin said.

5/8/13

Reference

P Marcellin, Q Xie, T Piratvisuth, et al. S-Collate cohort 'real-life' study: efficacy and safety of peginterferon alfa-2a (40kd) in 1233 patients with chronic hepatitis B according to Asian and Caucasian race. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 41.

StephenW

一些亚洲与聚乙二醇干扰素治疗慢性乙型肝炎的人可能会遇到更好的结果比白种人的若干措施上，虽然整体回应率是相似的，根据EASL国际肝病会议（2013年EASL）上个月在阿姆斯特丹进行了比较分析。研究还表明，早期乙肝表面抗原（HBsAg）的下降是在一些患者的治疗反应的预测。

核苷/核苷酸类似物抗病毒药物，如拉米夫定（3TC或拉米），恩替卡韦（博路定），替诺福韦（Viread的）治疗慢性乙型肝炎病毒（HBV）感染的中流砥柱。聚乙二醇干扰素是国际准则的建议，但不经常使用，由于成本和副作用。虽然抗病毒药物有效抑制病毒复制，干扰素可能会增加血清学反应涉及HBV抗原转阴和抗体血清转换的可能性。

巴黎大学的帕特里克MARCELLIN狄德罗介绍S-分页结果，前瞻性的跨国慢性乙型肝炎研究的主要目的的人的“现实生活”的队列研究，评估对治疗的预测HBsAg清除常规的临床实践。

以前的研究已经表明，治疗24周HBsAg的10％或更大的下降是与肝炎B“E”抗原（HBeAg）阴性患者之间的持久免疫控制，是一项为期24周的HBsAg水平低于1500 IU / mL的HBeAg阳性患者之间。

这项分析还看着治疗结果根据亚洲与白人的种族/族裔。 B型肝炎是流行在亚洲的很多，感染了许多人在生命的早期通过母亲传染给孩子。 “亚洲”和“白人”的含义产生了一些与会者的讨论，他指出，从印度次大陆的人可能是亚洲地区，但人类学白人，大部分的研究出现了比较东亚与白人患者。

该研究纳入592例HBeAg阳性的慢性丙型肝炎患者（亚洲455和137白人）和641例HBeAg阴性患者（224亚洲和417白人）。整体约70％为男性。平均年龄为年轻一点的HBeAg阳性而HBeAg阴性组（31年比38年）。亚洲人比白种人感染的持续时间较长（约16年比12年）和围产期收购更常见（约80％比30％）。亚洲人也有较高的ALT肝酶水平（183比142 IU / L，在e抗原阳性，148比101 IU / L之间的e抗原阴性）。

参与者随访24周开始治疗前180微克/周的聚乙二醇interferonalfa-2A（派罗欣）单药治疗48周。后续将继续通过3年后处理; Marcellin等6个月后的治疗结果。

结果

    寻找HBeAg阳性患者治疗后6个月，整体回应率是“类似”亚洲人和高加索人之间的所有端点。
    在这两个群体的一半达到HBV DNA水平<2000 IU /毫升，而17％和27％下降到<80 IU /毫升（接近统计学意义）。
    HBV DNA <2000 IU / mL的加ALT复常观察到在41％和37％，分别为20％和28％，实现了病毒载量低，加上HBeAg消失。
    然而，只有5％和6％，分别达到HBsAg消失，13％和9％，而达到HBsAg水平<100 IU /毫升。
    尽管有这些相似之处，亚洲经历了一个显着较大的下降，乙肝表面抗原，从基线相比，白种人，1.35和0.33日志，分别。
    39％的患者HBsAg水平<1500 IU / mL的12周治疗实现HBeAg消失和低HBV DNA，1500-20,000 IU / mL的14％和8％的那些> 20,000 IU / mL的比较。
    谈到HBeAg阴性的参与者，亚洲人比白种人更容易达到HBV DNA低于2000 IU / mL的单独（65％比53％），或在配合ALT复常率（57％比37％）。
    然而，6个月后的治疗反应率是类似的统计方面对HBV DNA <80国际单位/毫升（32％比23％），HBsAg消失（8％和4％），和HBsAg <100 IU / mL的（18％比13％）。
    在HBeAg阳性患者相比，HBeAg阴性的亚洲人和高加索人有相同的乙肝表面抗原从基线下降0.54和0.55日志，分别。
    治疗的安全性和耐受性没有显着差异亚洲和高加索患者。
    整体的副作用和严重不良事件率相似，5％和4％，分别因不良事件而终止治疗。

“在”现实生活“中设置，响应率[聚乙二醇化干扰素α-2a]亚洲和高加索慢性乙型肝炎患者之间的差异不显着，”研究人员得出结论，虽然他们注意到，更多的HBeAg阴性亚洲患者实现了低HBV DNA和ALT正常化。

“早期治疗乙肝表面抗原下降作为应对亚洲HBeAg阳性患者治疗后6个月的预测显示，实用，”他们补充说。

亚洲乙肝患者共同的信念，这项研究冲突“更难来对待。” “我想，干扰素应答亚洲人是相似的 - 也许甚至比 -  []白种人，Marcellin等说。”

13年5月8日

参考

P Marcellin等，Q谢，T Pi​​ratvisuth，等。 S-分页队列“现实生活”的研究：聚乙二醇化干扰素α-2a（40KD）根据亚洲和高加索人种在1233例慢性乙型肝炎的疗效及安全性。肝脏研究欧洲协会第48届年会（EASL 2013）。阿姆斯特丹。 2013年4月24-28日。摘要41。

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