2017 EASL慢乙肝领域新进展—抗病毒治疗肾脏、骨骼安#8131

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nbacl2003 wrote:
其实这篇文章问题不少的.
在比较HBVDNA和HBsAg下降程度时, respoonse组是分别与relapse组和nonresponse组进行比较的,然而在比较基线资料时,却将relapse组和nonresponse组合并成一组与 respoonse组进行比较, 即便是这样比较,基因型和HBV DNA载量的差别其实并不算小,最重要的是 respoonse组的ALT显著高于relapse组和nonresponse组, 那么 respoonse组HBsAG下降率高也不意外了. 从这样的一组人群中得出的结果并不可全信, 作者对于resonse组和relapse组两组患者的构成比较似乎在有意回避,况且就这么区区48例患者. 也就是欧洲人做的才能发Hepatology,换成中国人去投相同的文章, 那就两说了.


那我们讨论一下，Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B
Hepatology. 2009 Apr;49(4):1141-50
http://www3.interscience.wiley.com/journal/121542370/abstract
这篇是386位患者的研究结果。而且是多国合作，包括了10几家不同医院的研究，包括中国的南方医院。

2a in HBeAg-negative chronic hepatitis B.part1.rar (280.0k)

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Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B
Maurizia Rossana Brunetto 1 *§, Francesco Moriconi 1, Ferruccio Bonino 2, George K. K. Lau 3, Patrizia Farci 4, Cihan Yurdaydin 5, Teerha Piratvisuth 6, Kangxian Luo 7, Yuming Wang 8, Stephanos Hadziyannis 9, Eva Wolf 10, Philip McCloud 11, Richard Batrla 12, Patrick Marcellin 13
1UO Epatologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
2Scientific Direction, Foundation IRCCS Policlinico of Milan and University of Pisa, Italy
3Department of Medicine, Queen Mary Hospital, Hong Kong, China
4Dipartimento di Scienze Mediche, Università di Cagliari, Monserrato, Italy
5Department of Gastroenterology, University of Ankara, Turkey
6Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
7Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China
8Infectious Disease Department, Xinan Hospital, Chongqing, China
9Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece
10MUC Research, Munich, Germany
11Roche, Dee Why, Australia
12Roche, Basel, Switzerland
13Hôpital Beaujon, University of Paris, Clichy, France

email: Maurizia Rossana Brunetto ([email protected])

*Correspondence to Maurizia Rossana Brunetto, UO Epatologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

See Editorial on Page 1063
Potential conflict of interest: Dr. Brunetto is on the speakers' bureau of Roche. Dr. Bonino is a consultant for, advises, and is on the speakers' bureau of Abbott, Bristol-Myers Squibb, Gilead, and Novartis. He is also in the speakers' bureau of Schering-Plough. Dr. Lau is on the speakers' bureau of and received grants from Roche and Novartis. Dr. Piratvisuth advises and is on the speakers' bureau of Roche. He advises Novartis and Schering-Plough and is on the speaker's bureau of GlaxoSmith Kline. Dr. Hadziyannis is on the speakers' bureau of and received grants from Roche. He advises and received grants from Gilead. He advises Novartis and Bristol-Myers Squibb. Dr. McCloud owns stock in Roche.
§fax: (39)-050-995457

Funded by:
Roche

Abstract
We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log10 IU/mL) and D (median, 3.85 log10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, -0.71 and -0.67 log10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (-0.02 log10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to 400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. (HEPATOLOGY 2009;49:1141-1150.)

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Received: 25 June 2008; Accepted: 23 November 2008

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尝试翻译下摘要：

本文是针对PEG alpha-2a干扰素治疗慢性乙肝的大型多个国家合作研究。研究了血清HBsAg浓度的降低和预后反应与单独应用PEG alpha-2a、拉米夫定及二者联合用药的关系。参与该项目的537名病人中的386位，在治疗前、治疗结束（48周）和治疗结束（72周）后6个月时采用Abbott的Architect assay进行HBsAg定量测定。（PEG alpha-2a ，127人；PEG alpha-2a和拉米夫定联合用药，137人；拉米夫定单独用药，122人） 。治疗前HBsAg浓度因基因型不同而有所差异，基因型A（平均4.11log10 IU/ml），基因型D（平均3.85log10 IU/ml）患者浓度最高。PEG alpha-2a 治疗过程中HBsAg显著降低（单独或与拉米夫定联合用药，48周时分别平均下降-0.71和-0.67log10 IU/ml，P<0.001）。然而拉米夫定单独治疗未观察到降低（-0.02log10 IU/ml）。与拉米夫定单独用药（1%）相比，更多病人在单独使用PEG alpha-2a（21%）或PEG alpha-2a与拉米夫定联合用药（17%）治疗后HBsAg降低至<100 IU/ml的水平（P<0.001)。治疗后 HBsAg浓度与 6个月后HBV DNA抑制至<=400拷贝数/ml强烈相关。48周后HBsAg浓度<10 IU/ml 以及降低>1 log10 IU/ml与治疗结束3年后持续的HBsAg清除显著相关。

结论：HBeAg阴性慢性乙肝患者在使用PEG alpha-2a 过程中定量检测HBsAg，可能有助于确定能够治愈的患者和对治疗方案的优化。

根据雅培试剂盒说明书，针对不同亚型，估计1IU/ml=3-5.8ng/ml。其检测范围为：0.05-250 IU/ml。个人猜测，针对常见的adr亚型，其检测范围换算为ng/ml单位，则为：0.15-750ng/ml，远高于国内同类定量试剂（据本人所知，有的厂家标准曲线最高到150ng/ml）。

文中指出，DNA检测不适于监测慢性乙肝患者干扰素治疗时的持续抑制病毒反应。Although quantification of HBV DNA during treatment is appropriate for determining response to nucleoside analogs, it is not as suitable for monitoring the mechanisms responsible for the achievement of sustained antiviral response to interferon-based therapy in chronic hepatitis B patients.

因患者血清中HBsAg的浓度往往很高，远超出雅培试剂盒的检测范围，故文中对HBsAg的检测，直接采用了1：100稀释。对于100倍稀释后仍然超出检测范围的血样，改用1：1000重测。而100倍稀释，结果低于检出限的则改为不稀释，进行重测。
HBsAg was quantified using the Architect HBsAg assay (Abbott Laboratories, Abbott Park, IL; dynamic range, 0.05-250.0 IU/mL) after 1:100 dilution. Samples with HBsAg levels >250.0 IU/mL at 1:100 dilution were retested at a final dilution of 1:1,000. Samples with HBsAg levels <0.05 IU/mL at 1:100 dilution were retested undiluted.

这种稀释方式，值得我们在检测HBsAg时借鉴。

本文中有23名患者在随访中HBsAg达到<10IU/ml（占peginterferon alfa-2a治疗者总数比例为8.7%），其中12个治疗后3年HBsAg完全清除。

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pyk040207 wrote:
本人至今也没看到干扰素亦或核苷类似物对中国乙肝患者的疗效最科学可信的研究报告。中国有乙肝专家吗？


本文即为有中国参与的聚乙二醇干扰素国际合作研究，广州南方医院、重庆西南医院、香港Queen Mary Hospital都有参与。Hepatology杂志SCI影响因子约为10点几，足够权威、可信。

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我不知楼上诸位为何会得出这样的结论。我是1996年开始从事感染科，在我手上使用过干扰素的病人恐怕有过百了。从最初只有进口的干扰能（那时还是300万单位，疗程半年），到遍地开花的国产干扰素，剂量现在我们科室已经用到600万单位，疗程1～2年。但是，在之前使用如此之多的普通干扰素里，能对表面抗原起作用的微乎其微。而长效干扰素在这方面，就我跟进的病人来说（因为经济原因，大概也就10来个），的确显示出优势，虽然沒作正规统计，但是，出现表面抗原明显下降甚至阴转的病人肯定超过5例。效果好可能跟适应症掌握得好有关，我们一般是肝活检病理达G3或以上才会推荐较强抗病毒方案。所以，就我的经验来说，我不认同普通干扰素跟长效干扰素效果相仿的说法。

脚踩大病毒

今天我也逛了丁香园，从那里很受益

lingmaigui

感谢牛哥分享！

lingmaigui

转帖DXY

肝病患者用药注意事项

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本图是冲击疗法的主要理论依据所在。

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脚踩大病毒 发表于 2010-9-11 23:40
今天我也逛了丁香园，从那里很受益

在那里泡三个月，比这里泡三年强。
如果多些理论功底，再辅之以临床，
虽说不能当医生，但应付慢肝足够了。