Traditional Chinese Medicine May Perform

liver411

Better than Interferon or Lamivudine for Chronic Hepatitis B
                               
               

SUMMARY: Various traditional Chinese medicine (TCM) formulations were found to work as well as or better than the pharmaceutical drugs interferon and lamivudine for people with chronic hepatitis B, according to a joint U.S./Chinese review of clinical trials published in the February 2010 issue of Hepatology. While many of these studies were considered to be of poor quality according to Western drug testing standards, the review authors concluded that some TCM remedies appear effective and warrant further study.

               
                               

By Liz Highleyman

Chronic hepatitis B is major global health problem, but its impact is especially great in Asia. In China, it is estimated that approximately 120,000,000 people have chronic HBV infection. For centuries, the disease has been treated with traditional medicines.

Lingyi Zhang, Herbert Bonkovsky, and colleagues performed a meta-analysis of clinical trials of TCM formulations for treatment of chronic hepatitis B reported in China from 1998 through 2008.

An ancient book called the Yellow Emperor's Internal Classic indicates that TCM remedies have been used to treat chronic liver disease in China at least since 475 BCE, the authors noted as background. Today, TCM is still used extensively for the treatment of chronic hepatitis B in China, with some 80% of patients relying on Chinese remedies. While interferon alpha and lamivudine (Epivir-HBV) are often available, newer nucleoside/nucleotide analog drugs such as adefovir (Hepsera), entecavir (Baraclude), and tenofovir (Viread) are "prohibitively expensive" and not widely used, they noted.

Thousands of different herbs have been used in TCM formulations for liver disease, including astragalus (Huang Qi), bupleurum (Chai Hu), licorice root (Gan Cao), red sage (Dan Shen), rhubarb (Da Huang), and schisandra (Wu Wei Zi). "These TCM formulations are based on the collective wisdom of Chinese clinicians and practitioners, coupled with centuries of accumulated experience working with these herbs," the researchers wrote.

The review authors searched electronic databases (China National Knowledge Infrastructure and PubMed) to identify studies that either compared TCM formulations versus interferon (alpha-1b, alpha-2a, or alpha-2b, at least 3 million units administered 3 times per week for at least 3 months) or lamivudine (at least 100 mg administered once-daily for at least 30 consecutive days), or that added Chinese remedies to interferon or lamivudine to see if the combination worked better than the Western drugs alone. They also looked at which specific Chinese herbs are used most often.

The initial search included both randomized controlled trials (RCTs) -- the "gold standard" for Western drug testing -- and other types of studies that reported objective outcome measures such as serum alanine aminotransferase (ALT) normalization, HBV DNA viral load clearance, or hepatitis B "e" antigen (HBeAg) loss.

A total of 643 reports were selected for inclusion (596 in Chinese, 47 in English). Of these, 487 were clinical trials (356 RCT and 131 non-RCT), 80 were pre-clinical experimental studies, and 76 were summaries of non-randomized clinical experience.

Out of these studies, the researchers identified 53 RCTs that reported random allocation of patients with chronic hepatitis B to treatment with TCM formulations; these trials met the inclusion criteria and were used in the meta-analysis. The studies used a variety of TCM formulations, with an average of 9 ingredients, but approximately 50%-60% of the herbs overlapped across different formulations.

Overall, the quality of studies was judged to be "poor"; 16 (27%) of the 53 RCTs had Jadad scores (a standard algorithm for assessing trials) of 3, while the rest (73%) had scores of 2. None of the reports described methods used for randomization or whether they were double-blind, single-blind, or unblinded.

Among the 53 selected RCTs, 16 (1918 total participants) compared responses in patients receiving TCM formulations alone versus interferon, 6 RCTs (723 total participants) compared TCM alone versus lamivudine,18 trials (1738 total participants) compared TCM plus interferon versus interferon alone, and another 14 trials (1548 total participants) compared TCM plus lamivudine versus lamivudine alone

Results
        A total of 203 different herbs were included in 230 TCM formulations for the treatment of chronic hepatitis B.
        TCM formulations alone had a significantly greater beneficial effect than interferon for ALT normalization (odds ratio [OR] 2.42, or 2.4-fold greater; P = 0.0003).
        Chinese formulations and interferon had a statistically similar likelihood of reducing HBeAg (OR 1.60; P = 0.07).
        TCM and interferon also performed similarly with regard to HBV viral load clearance (OR 1.31; P = 0.20).
        TCM formulations were significantly more effective than lamivudine for normalizing ALT (OR 1.96, or nearly twice as effective; P = 0.01).
        TCM and lamivudine showed no significant difference in likelihood of reducing HBeAg (OR 1.57; P = 0.36).
        Again, TCM and lamivudine were about equally likely to produce HBV DNA clearance (OR 1.20; P = 0.59).
        When used in combination, TCM plus interferon enhanced antiviral activity and liver function improvement compared with interferon alone:
         
        ALT normalization: OR 3.07, or about 3-fold greater benefit (P < 0.00001);
        HBeAg reduction: OR 2.17, or about twice the benefit (P < 0.00001);
        HBV DNA clearance: OR 2.05, again about twice the benefit (P < 0.00001).
        TCM formulations plus lamivudine were also significantly more effective than lamivudine alone:
        ALT normalization: OR 3.40 (P < 0.00001).
        HBeAg reduction: OR 2.54 (P < 0.00001);
        HBV DNA clearance: OR 3.20 (P < 0.00001);
        In a similar analysis of the 16 RCTs of higher technical quality (Jadad scores of 3), the pattern of the results were similar.
        Among 20 RCTs that included information about adverse events, no serious adverse side effects of TCM formulations were reported.

Based on these findings, the review authors concluded, "Some TCMs seem effective as alternative remedies for patients with chronic hepatitis B, suggesting that further study of TCMs in the treatment of chronic hepatitis B is warranted, both in preclinical models of HBV infection and in higher quality RCTs worldwide."

"Our meta-analysis suggests that in patients with chronic hepatitis B, (1) TCMs have a similar curative effect as interferon/lamivudine on antiviral activity as evidenced by the loss of serum HBeAg and HBV DNA; (2) TCMs have a better effect on normalization of serum ALT; and (3) TCMs enhance interferon and lamivudine antiviral activity and improvement of liver function," they elaborated in their discussion.

"It is noteworthy that there were no reported serious adverse events associated with the combinations of TCM studied," they added. "As used in China, these formulations seem to be very well tolerated, although many reports did not include data on adverse effects of therapy."

Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases, and Metabolism Laboratory, NC; McColl-Lockwood Laboratory, Carolinas Medical Center, Charlotte, NC; Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China; Department of Biology, University of North Carolina at Charlotte, Charlotte, NC; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; Departments of Medicine and Molecular, Microbial & Structural Biology, University of Connecticut Health Center, Farmington, CT.

4/6/10

Reference
L Zhang, G Wang, W Hou, and others. Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: An analytical review. Hepatology 51(2): 690-698 (Free full text). February 2010.

走遍四方

既然TCM这么好，哪家医院在用的呢

特深沉

神棍？

利益链

中药，确实有效，但不同的医生使用的效果大不相同，有人将你的小三旭治成大三阳，有的将你的大三阳治成小三阳。

afang1989

Highleyman由Liz

慢性乙型肝炎是全球主要的健康问题，但其影响是很大的，特别是在亚洲。在中国，据估计，大约有1.2亿人患有慢性乙肝病毒感染。几个世纪以来，该病已与传统的药物治疗。

灵益章，赫伯特Bonkovsky，和同事进行了一项对治疗慢性乙型肝炎的中医配方治疗临床试验的荟萃分析报告在中国从1998年到2008年。

一个古老的书，名为黄帝内经表明，中医药的补救措施已被用于治疗至少自公元前475在中国慢性肝病，作者指出，作为背景。今天，中医药仍然是广泛用于治疗慢性乙型肝炎的治疗在中国，一些对中国80％的患者靠救济。虽然干扰素α和拉米夫定（拉米乙肝病毒）通常可用，较新的核苷/核苷酸模拟药物，如阿德福韦（Hepsera），恩替卡韦（恩替卡韦），和替诺福韦（品牌名称为Viread）是“昂贵”，而不是被广泛使用，他们注意到。

成千上万不同中药已用于医药制剂肝脏疾病，包括黄芪（黄琦），柴胡（柴虎），甘草（甘草），丹参（丹参），大黄（大黄），和五味子（五味子）。 “这些中药制剂在临床中积累经验，并与这些草药医生的工作，加上百年，集体智慧的基础上，”研究人员写道。

回顾作者检索（中国国家知识基础设施和PubMed）电子数据库，以确定中药制剂相比，要么与干扰素（α- 1b中，α- 2a干扰素，或α- 2b干扰素，至少有300万单位管辖每周3次，在研究至少3个月）或拉米夫定（至少100毫克管理至少连续30天每日一次），或者说中国补救措施，以干扰素或拉米夫定，看看它们搭配在一起优于单独西药。他们还研究了哪些具体的中药是最常用。

最初的搜索既包括随机对照试验（RCT） - 的“黄金标准西药检验” - 报告和研究，如血清丙氨酸转氨酶（ALT）正常化，HBV DNA的病毒载量的通关措施的其他类型的客观结果，或者乙肝“e”的抗原（HBeAg）的损失。

一个643的报告一共选出列入（中文，英文47 596）。其中，487人的临床试验（RCT的356和131非随机对照试验），80人临床前实验研究，以及76人的非随机的临床经验总结。

在这些研究中，研究人员发现53个随机对照试验的报告慢性乙型肝炎与中医配方治疗的病人随机分配，这些试验符合纳入标准并在元分析。这些研究使用了9成分的中药配方平均多种，但约有50％-60对不同配方的中药重叠％。

总体而言，研究的质量被认为是“穷人”，16（27％的53个随机对照试验）已加达德分数（标准为评估试验算法3），而其余（73％）的2分。没有任何一份报告描述了随机使用的方法，或它们是否双盲，单盲，非盲。

在选定的53个随机对照试验，16（共1918人参加）相比，接受干扰素与中药制剂单，6篇（共723人参加）中药与拉米夫定相比，仅18个试验（共1738人参加）相比，中药加干扰素与干扰素单独放射治疗的反应，另有14个试验（共1548人参加）相比，中药加拉米夫定与拉米夫定单

结果
        一共有203种天然植物被列入230中医对慢性乙型肝炎的治疗制剂
        中药制剂仅进行了比ALT正常化（干扰素显着有益的影响更大胜算比[OR] 2.42，或2.4倍以上; P值0.0003）。
        中国配方和干扰素减少了HBeAg的（或1.60统计学类似的可能性; P值0.07）。
        中医和干扰素方面也进行乙肝病毒载量，清除或1.31（同样，P值0.20）。
        中药制剂显着多于拉米夫定有效正常化ALT键（或1.96，或有效的近两倍; P值0.01）。
        中医和拉米夫定在减少无e抗原（或1.57的可能性显着性差异; P值0.36）。
        同样，中医和拉米夫定大约同样可能产生乙肝病毒DNA的清除或1.20（; P值0.59）。
        当结合使用，中药加干扰素抗病毒活性，增强肝功能的改善与干扰素相比，仅：
           
        ALT正常化：或3.07，或约3倍，更大的效益性（P <0.00001）;
        HBeAg的减少：或2.17，或两倍的利益性（P <0.00001）;
        乙肝病毒DNA的检查：或2.05，再次约两倍的效益性（P <0.00001）。
        拉米夫定加中药制剂均显着高于拉米夫定更有效的特例：
        ALT正常化：或3.40性（P <0.00001）。
        HBeAg的减少：或2.54性（P <0.00001）;
        乙肝病毒DNA的检查：或3.20性（P <0.00001）;
        在一个较高的技术质量（加达德3分）的16个随机对照试验类似的分析，结果的模式相似。
        其中20个随机对照试验，其中包括信息的不良事件，无严重副作用的中药制剂效果的报告。

基于这些发现，回顾作者总结说：“看起来就像有些中药对慢性乙型肝炎患者的替代补救措施有效，这表明中药治疗慢性乙型肝炎的治疗是需要进一步研究，无论是在乙肝病毒感染和临床前模型更高质量的随机对照试验全世界。“

“我们的荟萃分析表明，在慢性乙型肝炎患者，（1）中药也有类似的干扰素疗效/拉米夫定抗病毒活性的血清HBeAg和HBV DNA的损失;证明（2）中药获得更好的效果对血清ALT正常化;及（3）加强中药干扰素和拉米夫定抗病毒活性和肝功能的改善，“他们阐述了他们的讨论。

“值得注意的是，有没有报告与中医有关的严重不良事件的组合研究，”他们说。他说：“在中国使用，这些配方似乎很耐受性良好，尽管许多报告没有包括治疗不良影响的数据。”

肝胆胰中心和肝脏，消化系统疾病，代谢实验室，数控;麦科尔-洛克伍德实验室，卡罗莱纳州医学中心，夏洛特，北卡罗来纳州的临床医科学研究所，中国中日友好医院，北京，中国;部生物，北卡罗莱纳大学夏洛特，夏洛特，北卡罗来纳州，北卡罗莱纳大学教堂山，查山，数控医学系医学和分子，微生物与结构生物学，康涅狄格州卫生中心，法明顿，大学院系的CT 。

4/6/10

参考
L章地下王，钨侯等。现代临床研究传统中医药治疗慢性乙型肝炎在中国：一个分析性审查。肝病51（2）：690-698（免费全文）。 2010年2

渺小渺

感谢战友afang1989，谢谢了