榮陽治肝湯對慢性C型肝炎病人之療效評估一隨機雙盲對照及交叉研究

黃信彰
行政院國軍退除役官兵輔導委員會臺北榮民總醫院
慢性Ｃ型肝炎的病人約有百分之十至三十在十至二十年之追蹤會發展成肝硬化，甚至導致成肝癌發生。因此，慢性Ｃ型肝炎雖然時常沒有症狀，但是，積極而有效的治療確是必須的。干擾素在慢性Ｃ型肝炎的治療上佔了一個重要的角色，是第一個被核准用來治療慢性型肝炎之 西藥，但是其副作用及停藥後的高復發率，使得干擾素的治療效果大打折扣。目前合併使用干擾素加上抗病毒藥物雷巴威靈（ribavirin）須可使治療成功率加倍，但ribavirin造成溶血之副作用仍使部份病人無法忍受。而傳統的中藥治療慢性Ｃ肝炎已為民間廣為使用且因較無副作用而為病人所接受，但因尚未有一明確的科學研究及嚴謹的血清生化及病毒核酸指數作為治療效果的評估，所以療效尚未被確認。
本研究目的即在探討榮陽治肝湯 (龍膽瀉肝湯、加味逍遙散、丹參和厚补的組合，是中醫界常用來治療肝炎且在細胞及動物研究模式中具抗病毒、抗發炎、抗氧化及免疫調節功能) 在慢性Ｃ型肝炎病人的治療療效，尤其瞭解其對血清肝轉氨酶及Ｃ型肝炎病毒核酸的影響。研究對象為曾經接受干擾素為主的標準治療，且治療失敗(含不反應及復發)，或不適合接受干擾素治療的慢性C型肝炎患者，第一年我們將收集三十六位符合收案條件之慢性Ｃ型肝炎病人且經中醫師辯證屬於肝鬱血瘀合併肝經濕熱的證型者同時願意接受榮陽治肝湯治療者，研究對象隨機分成二組，一組（18人）給予榮陽治肝湯每天三次，每次五公克，為期十二週，另一組（18人）給予外形及味道相似但內容為澱粉之安慰劑，每天服用三次，為期十二週，於十二週結束後，停藥二週，再將二組互換，原來接受榮陽治肝湯者換成接受安慰劑，原來接受安慰劑組換成接受榮陽治肝湯為期十二週。研究治療期間定期評估其臨床症狀、副作用以及中醫證型變化，同時抽血偵測血清肝轉氨酶以及血中Ｃ型肝炎病毒核酸濃度之變化。更利用疲倦量表及生活品質問卷來了解對病人生活品質之影響。預期將可知道榮陽治肝湯是否對慢性Ｃ型肝炎病人是否有降血中肝轉氨酶以及血中Ｃ型肝炎病毒核酸濃度之能力。研究第二年我們將針對有療效之慢性Ｃ型肝炎病人進行二十四週之治療及評估其停藥後二十四週之長期持續療效 (sustained response)，期望能以嚴謹及科學的研究方法來評估榮陽治肝湯治療慢性Ｃ型肝炎的療效及安全性。本研究將以嚴謹及科學的研究方法來評估榮陽治肝湯治療慢性Ｃ型肝炎的療效及安全性，本研究結果將提供中西醫界在治療慢性Ｃ型肝炎之重要參考。
關鍵字：榮陽治肝湯、慢性Ｃ型肝炎、血清肝轉氨酶、Ｃ型肝炎病毒核酸、中醫證型、疲倦量表、生活品質問卷

Clinical efficacy of Rong-Yang-Jyh-Gan-Tang on patients with chronic hepatitis C: a double-blinded randomized placebo-controlled cross-over study(2-1)

Hwang SJ
10 to 30% of patients with chronic hepatitis C virus (HCV) infection will progressive insidiously to cirrhosis after 10 to 20 years’ follow-up, and some will develop hepatocellular carcinoma. So, the treatment of patients with chronic hepatitis C is urgent. Interferon is the first drug approved for treatment of chronic hepatitis C. However, the results were unsatisfactory due to high relapse rate and side effects. Combination of interferon with ribavirin has improved the sustained response rate in treating chronic hepatitis C patients, but the side effects of hemolysis due to ribavirin often lead to intolerance of patients. Traditional Chinese medicine has been widely used by the publics in Taiwan due to its safety and good patients’ tolerance. However, the efficacy of traditional Chinese medicine has not been confirmed because there were no evidence-based results or scientific parameters such as serum liver transaminase or viral load available in the evaluation of treatment response.
This study evaluates the clinical efficacy of Rong-Yang-Jyh-Gan-Tang (a combination of long-dan-xie-gan-tang, jia-wei-xia-yao-san, dan-shen and hou-po) on patients with chronic hepatitis C. Rong-Yang-Jyh-Gan-Tang and its ingredients have been proven to have in vitro or in vivo anti-viral, anti-inflammatory, immune modulation effect, and been commonly used in clinical practice of Chinese Medicine in Taiwan. The purpose of this study is to evaluate the clinical efficacy of Rong-Yang-Jyh-Gan-Tang in treating patients with chronic hepatitis C, particularly emphasize on the effect on serum liver transaminase and HCV RNA. In the first year, we will enroll 36 patients with chronic hepatitis C who were not response or not suitable for standard interferon-based therapy into this study. Patients will be diagnosed first by Chinese herbal doctor to identified as “dampness heat stasis” and “liver Qi stagnation” by Bian-Zheng-lun-zhi and then randomized and allocated to receive Rong-Yang-Jyh-Gan-Tang/placebo 5gm three time a days (n=18) or placebo (n=18) for 12weeks. After 2 weeks’ washout period, patients will be crossed over to receive placebo/ Rong-Yang-Jyh-Gan-Tang for another 12 weeks. In the second year project, patients who had response will receive a 24 weeks course of Rong-Yang-Jyh-Gan-Tang to evaluate the sustained response 24 weeks after stopping treatment. Patients will return to clinics as schedule and blood tests for complete blood count, liver biochemistries and HCV RNA will be performed. Clinical symptoms and side effects of Rong-Yang-Jyh-Gan-Tang will also be recorded in detail during and after treatment. We also apply Chinese Medicine symptoms score, fatigue severity score and quality of life questionnaire to evaluate the change of quality of life in these patients. This study will in a rigid and scientific way to evaluate the clinical efficacy of Rong-Yang-Jyh-Gan-Tang on patients with chronic hepatitis C.
關鍵字：Rong-Yang-Jyh-Gan-Tang, chronic hepatitis C, serum liver transaminase, hepatitis C viral RNA, Bian-Zheng-lun-zhi, Fatigue severity score, quality of life