华盛顿邮报有关拉米夫定危险性的报道

　　　　[关键词]贺普汀 慢性乙型肝炎 葛兰素威康

　　近来对长期应用拉米夫定治疗慢性乙型肝炎可能存在危险性是乙肝抗病毒治疗的一个热点问题，越来越受到临床医师的重视。现提供一篇2001年3月发表于华盛顿邮报的文章，并能与医学界同仁就此问题进行交流与探讨。

　　----编者

　　Researcher Says GlaxoSmithKline plays Down Problems In Hepatitis Treatment

　　作者：Deborah Nelson

　　Washington Post Staff Writer

　　Sunday, March 18,2001;Page A 14

　　Peborah Nelson

　　华盛顿邮报

　　2001年3月18日，星期天

　　制药行业巨人的编造掩盖了拉米夫定的危险性

　　研究人员说葛兰素故意对乙肝治疗存在的危险轻描淡写

　　HONG KONG-when pharmaceutical giant Glaxo Wellcome Inc. came to this crowded Asian city several years ago to test a new drug for hepatitis B, researcher Nacny Leung was pleased with the early results in a short course of treatment the drug showed positive effects on many liver patients at her university hospital.

　　香港-几年前，当制药行业巨人葛兰素威康公司来到这个亚洲拥挤的城市试验治疗乙型肝炎的新药时，研究员Nancy 梁对早期结果非常满意。经过短期治疗后，这个新药在她所在的大学附属医院的肝病病人身上起到了积极作用。

　　But over time, she began detecting mutant viruses in the blood of participants who stayed on the drug longer than a year. She promptly reported the disturbing development to Glaxo.

　　"Most virologists" Leung said ,"do not want to create a new virus."

　　Glaxo assured her that the new viruses. Though drug-resistant, appeared to be relatively benign..She said.

　　但随着时间的延长，在那些治疗时间超过一年的病人血液内检测到突变病毒。她立即向葛兰素公司报告了这一令人担忧的重大事件。

　　"大多数病毒学家不希望制造出新型病毒"梁评价说。

　　葛兰素安慰她说，新病毒虽然耐药，但似乎没有太大危险。

　　Then, in the summer of 1997,a 36-year-old patient. She Yun-Ki, fell mortally ill while taking the drug. Goaxo listed his cause of death as peritonitis, but Leung said that was misleading. He had developed mutant viruses, she said, and his liver failed. The peritonitis was the last in a cascade of deadly ailments that followed, she said.

　　接下来，在1997年夏，一位36岁的病人She Yun-Ki，在服用拉米夫定后死亡。葛兰素把他的死因归因于腹膜炎，但梁教授说这是误导。事实上，病人体内的病毒已经突变。引起肝功能不全。腹膜炎只是肝功能不全后一系列并发症中最严重的一种。

　　The death left her shaken, and she took a more critical view of the rapidly spreading mutant viruses among patients receiving long-term treatment, joining a growing number of liver specialists who say the drug should not be used for more than a year.

　　这例病人的死亡震惊了梁教授，她于是采取了一种更加批判性的态度，来对待在长期治疗病人中快速传播的突变型病毒问题。她也因此加入了不断扩大的反对拉米夫定用药超过一年的肝病专家队伍中。

　　But that view is on a collision course with Glaxo's efforts to promote more and longer use of the drug lamivudine, which is now sold in 60countries and last year accounted for $108 million in sales.Glaxo officials say long-term treatment is safe and effective for mot patients.

　　但梁的观点显然与葛兰素推行更多、更长应用拉米夫定的努力背道而驰。拉米夫定已在60个国家获准上市。去年的销售额占10.8亿美元。葛兰素官员称对多数病人而言长期治疗安全而有效。

　　Leung said Glaxo has tried to suppress concerns about the drug, attaching her name to upbeat research reports that she didn't approve and churning out data that mask the drug's problems. Glaxo's failure to adequately acknowledge lamivudine's problems has led to a "mood of mistrust and discontent" among Asian liver specialists. She said.

　　梁说，葛兰素尽力想掩盖对拉米夫定的担忧，将她的名字附在未经其本人同意的乐观的研究报告上，并编造了大量资料来掩盖该病的问题。葛兰素不能完全承认拉米夫定的问题已经导致亚洲肝病学家对公司的"不信任和不满的情绪"。

　　Fraser Gray, who leads Glaxo's lamivudine development team, said he was not aware of any unhappiness among Asian researchers over the company's interpretation of their data. Glaxo works closely with all outside researchers to make sure they agree with the company's scientific claims of success, he said.

　　领导拉米夫定推广小组的Fraser Gray说，他没有意识到亚洲研究人员对葛兰素公司对他们的材料解释有任何不满。葛兰素公司与所有公司外的研究人员密切工作来保证他们与公司成功的科学主张相一致。

　　Leung sees it differently. "We are too much controlled by them." She said. "I feel like I've been constantly, positively spun."

　　梁并不这样看，"我们被他们控制的太多，我感觉好象一直在被他们欺骗着。"

　　The mutant virus controversy illustrates a new global twist in an ongoing debate in U.S. scientific circles over whether drug companies with massive research budgets exert too much control over human testing and the publication of findings in medical journals.

　　Academic researchers who rely on industry money to stay afloat are being pressured by drug companies to put a favorable spin on clinical trial results, said Marcia angell. Former editor in chief of the New England Journal of Medicine.

　　突变病毒的争论说明了在美国科学界正在进行的争论中出现一个全球性转折，这个争论的焦点是拥有大量科研预算的制药公司是否对人类试验及在医学刊物上发表研究结果施加太多的控制。

　　一些学术研究人员依靠公司赞助的钱来维持研究工作的运转。这些人正在被制药公司强迫拿出有利于公司利益的临床试验结果，前新英格兰杂志主编Marcia Angell说。

　　Lamivudine is prescribed for chronic hepatitis B. A potentially fatal liver disease that infects 350 million people around the world. In the United States, the virus spreads largely through illegal drug use and unprotected sex. In Asia, where three-quartets of the hepatitis B population resides the disease is primarily passed from mother to baby. Chronic carriers may live normal lives. But they suffer periodic attacks that can eventually cause liver failure or cancer.

　　拉米夫定用于治疗慢性乙型肝炎，这种病是一种潜在的致命性疾病。在全世界感染约3.5亿人。在美国，病毒的传播主要通过毒品及未保护的性交。在亚洲，乙型肝炎占全世界的3/4，而且主要是从母亲传给婴儿。慢性病毒携带者可能过正常的生活，但他们会周期性的发生肝病。最终导致肝衰竭及肝癌。

　　Glaxo, now GlaxoSmithKline, began worldwide lamivudine testing in the mid-1990s and is still studying its long-term usefulness. The FDA approved lamivudine for hepatitis B in 1998, based on one-year results from research carried our by Leung and others in Asia, Europe and the United States.

　　葛兰素，现在叫GlaxoSmithKline，于1990年中期开始全球性拉米夫定试验，目前仍在对其长期应用进行研究。FDA批准拉米夫定用于治疗乙型肝炎是在1998年，批准的根据是由梁等在亚洲、欧洲及美国进行的为期一年的研究结果。

　　Since hen ,there has been good and bad news on lamivudine. While there is evidence that long-term treatment produces lasting improvement in some patients the mutant virus risk rises dramatically over time-infecting one-fourth of study participants after one year of treatment and 67 percent after four years.

　　从那时起，对拉米夫定的新闻就有好有坏，尽管有证据表明，长期应用在一些病人会带来持续的改善，但随着时间的延长，出现病毒突变的危险急剧增加，治疗一年的病人有1/4，而在4年的病人高达67%发生突变。

　　Patients with the mutant viruses have suffered relapses and several have died. Some have had to forgo liver transplants, because the risk of complications is higher. On the other hand, many appear no worse of initially and continue to show improvement on lamivudine, leading Glaxo to recommend they stay on the drug. The long-term consequences of the mutant viruses are not yet known.

　　感染突变病毒的病人会病情复常，有几例已经死亡。由于并发症的危险更高，有些病人已经不得不放弃肝移植。另一方面，许多病人用药开始时病情未出现恶化，并有改善，葛兰素因此建议继续用药。但突变病毒的长期结果目前还无法预测。

　　A recent study by Liaw Yun-San, a leading Taiwan hepatologist, uncovered more frequent and severe liver attacks in lamivudine patients with the mutant than Glaxo had been reporting .He said his own and other studies led him to conclude that the mutant viruses should be avoided until an understand .

　　接下来的事情就不是模棱两可的了，梁说：葛兰素在一次为国际科学会议给她的幻灯片中对她的研究结果提供了误导信息。有些服用拉米夫定病人的肝脏炎症有急剧加重。转氨酶出现尖锋状增高，但公司的图表却显示为一个平坦、均匀的线，仅在正常肝脏酶水平的附近波动。公司用平均值报导尖锋弄平，而不是用原始的单个记录，他们说这是为了便于理解。

　　Last summer ,Leung said she received an e-mail with several study abstracts that Glaxo had written under her name, without her input, for distribution at a conference at the National Institutes of Health in Bethesda. Her reservations about long-term treatment weren't reflected in Glaxo's upbeat conclusions.

　　Leung said she tried to correct the written record in her oral pressentation, but the damage had been done , because the abstracts are read and cited internationally ."It doesn't matter if Nancy creates a fuss at a presentation, because the whole world reads the abstract." She said .

　　去年夏天，梁收到一封电子邮件，内容为葛兰素公司以她的名义写 的几个研究的摘要，用来在Bethesda 举行的NIH的会议上发放，但事先未经她的审阅。在葛兰素乐观的结论中未能反映出她对长期治疗的保留意见。

　　梁说，在她的口头报告中，她极力纠正葛兰素的错误，但损失已经造成，因为那些摘要已经被广泛阅读及在国际上广泛应用。"Nancy在大会上大惊小怪已无关紧要，因为全世界都已经阅读了那些摘要"梁说。

　　Glaxo spokeswoman Nancy Jo Peparek said there may have been a "breakdown in the process" in the rush to get the abstracts done for the NIH conference." This unfortunate incident has not disrupted the good working relationship we have with her." Pekarck said .

　　In December, Glaxo sought Leung's signature for this year's updated research report for the FDA. She read the report and , four days later, fired back a dozen questions. Later the same say, she said, the company informed her that it was too late to address her concerns , because the report had already been "signed off internally " and submitted.

　　葛兰素发言人Pekarek 说，可能在急于为NIH会议准备摘要的过程中发生了问题。"这件不幸的事件并没有破坏我们与梁的良好关系"，Pekarek说。

　　在十二月，葛兰素要梁为本年度给FDA的最新研究报告签字，她阅读了报告，并在4天后给公司提了许多问题。但在当天晚些时候，公司告诉她现在提出她的担忧为时已晚，因为报告已被公司内部"签字正式批准"并已上交。

　　Pekarek confirmed that company had given the FDA the long-term treatment data on lamivudine, including the Asian study results.

　　Pekarek证实了公司已将长期治疗的资料交给FDA，包括亚洲的研究结果。

　　Other lamivudine researchers described varying degrees of company influence. Another HongKong researcher said Glaxo routinely writes abstracts and scientific papers under his name, although he usually reviews them first. A Taiwan scientist said he has asked Glaxo to remove his name from a paper that he considered too positive. In the United States, one researcher said he does his own analyses, while another said the company often writes the first draft of papers but he revises them ..

　　其他拉米夫定研究人员也描述了葛兰素公司对他们不同程度的影响。另一名香港研究人员说，葛兰素通常会以他的名言写一些摘要或论文。一位台湾科学家说，他已经要求葛兰素从一篇论文中把他的名字去掉。原因是结果太乐观。在美国，一位研究人员说，他自己分析，而另外有人说，公司把论文的第一份草稿写好，由他修改。

　　Some people work better doing a draft on their own ,and some prefer that we do it " said Gray of Glaxo, who called Leung's experience a " rare occurrence."

　　Pekared said the company doesn't skew research data in its favor. The company conducts symposia and distributes treatment guidelines addressing the mutant virus risk, she said . Potential problems are disclosed in all scientific and marketing materials, she said.

　　有些人更努力地工作，自己写草稿，而有些人喜欢由我们来做。葛兰素的Gray说，梁的经验是极个别的情况。

　　Pekarek说公司并没有为了自己的利益篆改研究数据，公司针对突变病毒的问题举行研讨会。分发治疗指南。她说在所有科学及市场材料中都公布了这些潜在的问题。

　　Leung said she gets those materials but disagrees that the risks and adequately presented. A Glaxo flier last month promoted a four-year regimen of lamivudine, with favorable statistics superimposed on a Pacific island scene.

　　"And only small print on drug resistance." Leung said. " Do we as a medical profession need to dress up in bikinis to counter them?"

　　梁说他得到了那些资料，但不同意他们将危险性充分说明的说法。上月葛兰素分发了推动4年拉米夫定方案的小册子，在太平洋岛屿的背景上加上了对自己有利的统计数字。

　　 "只有很小的部分提到耐药的问题"梁说，"作为医学专业人士，难道要让我们穿上比基尼到岛屿上去反对他们吗？"