Retrospective Cohort Study on Clinical Value of Huaier Granule in Postoperative Patients with Liver Transplantation for Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Wei , YAN Lnan , WU Hong , YANG Jiayin , WANG Wentao , XU Mingqing

Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Hepatic carcinoma; Liver transplantation; Huaier granule; Recurrence; Metastasis; Immune rejection

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Objective To study the effect of Huaier granule on the recurrence and metastasis of hepatocellular carcinoma (HCC) and immune rejection in the postoperative patients with liver transplantation for HCC. Methods Twenty-eight patients of liver transplantation for HCC who had taken Huaier granule orally for more than 6 months from September 2001 to March 2007 in West China Hospital were included as treatment group, and other 56 patients of liver transplantation for HCC who didn’t take any Huaier granule in the same time were included as the control group according to the same stage of TNM, degree of tumor differentiation (Edmondson grading) respectively with the treatment group. The method of retrospective cohort study was used to compare the incidence of immune rejection and the 6-month, 1-year, and 2-year recurrence and metastasis of HCC, disease free survival rate, and survival rate between two groups after 2 years’ follow-up beginning from the date of surgery. Results The 6-month, 1-year, and 2-year tumor recurrence and metastasis incidences in treatment group were 14.3%, 32.1%, and 39.3% respectively, which were 23.2%, 32.1%, and 50.0% respectively in control group, and the 2-year tumor recurrence and metastasis incidence of the treatment group was lower than that of the control group. The 6-month, 1-year, and 2-year disease free survival rates in treatment group were 85.7%, 67.5%, and 60.0% respectively, which were 76.7%, 67.6%, and 49.3% respectively in control group, and the 2-year disease free survival rate of treatment group was higher than that of the control group. The 6-month, 1-year, 2-year survival rates in treatment group were 92.9%, 78.6%, and 67.9% respectively, which were 89.3%, 75.0%, and 62.5% respectively in control group. But the 2-year tumor recurrence and metastasis incidence (P=0.353), 2-year disease free survival curve (P=0.386), and 2-year survival curve (P=0.620) were not significantly different between two groups. The incidence of immune rejection was 14.29% in the treatment group and 16.07% in the control group, which was not significantly different between the two groups (P=0.831). Conclusions Huaier granule can increase the 2-year tumor-free survival rate and restrain the recurrence and metastasis of HCC, and does not increase the incidence of immune rejection. Huaier granule as a treatment of HCC in patients with liver transplantation is safe and effective.

Citation： HUANG Wei,YAN Lnan,WU Hong,YANG Jiayin,WANG Wentao,XU Mingqing. Retrospective Cohort Study on Clinical Value of Huaier Granule in Postoperative Patients with Liver Transplantation for Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(6): 547-551. doi: Copy

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3.	Steinmüller T, Jonas S, Neuhaus P. Review article: liver transplantation for hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2003; 17 Suppl 2: 138-144.
4.	Molmenti EP, Klintmalm GB. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry [J]. Liver Transpl, 2002; 8(9): 736-748.
5.	郑树森, 吴健. 肝移植治疗原发性肝癌的价值 [J]. 中国医学科学院学报, 2008; 30(4): 366-370.
6.	贺轶锋, 樊嘉, 周俭, 等. 影响肝癌肝移植预后的高危因素分析及诊治经验 [J]. 中华医学杂志, 2006; 86(18): 1232-1235.
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8.	赵建军, 蔡建强, 毕新宇. 槐耳颗粒对原发性肝癌术后转移复发的影响 [J]. 中国综合临床, 2007; 23(3): 245-247.
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10.	Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis [J]. N Engl J Med, 1996; 334(11): 693-699.
11.	Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria [J]. Liver Transpl, 2002; 8(9): 765-774.
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13.	许戈良, 荚卫东, 马金良, 等. 槐耳清膏体外抑制血管生成的实验研究 [J]. 中国药理学通报, 2003; 19(12): 1410-1412.
14.	陈大兴, 陈孝平, 张万广. 槐耳清膏治疗肝癌的实验研究 [J]. 中国普通外科杂志, 2004; 13（8）: 578-582.
15.	王家顿, 谢大兴, 陈金明, 等. 抗癌药物诱导Molt-4细胞凋亡的周期时相性分析 [J]. 中国肿瘤, 2002; 11(9): 533-534.
16.	程若川, 汤礼贵, 兰丽琴. 槐耳浸膏诱导人直肠癌HR8348细胞凋亡的实验研究 [J]. 中国肿瘤, 2003; 12(2): 122-124.
17.	李立新, 叶胜龙, 王艳红, 等. 槐耳浸膏诱导肝癌细胞凋亡的实验研究 [J]. 中国临床医学, 2005; 12(6): 1152-1153.
18.	王建忠, 程若川. 槐耳的研制及临床应用 [J]. 井冈山医专学报, 2003; 10(1): 15-16.
19.	陈慎宝, 丁如宁. 槐耳菌质成分对小鼠免疫功能的影响 [J]. 食用菌学报, 1995; 2(1): 21-25.
20.	刘念, 耿小平, 朱立新, 等. 槐耳清膏体外逆转人肝细胞HepG2/ADM多药耐药性 [J].中华肝胆外科杂志, 2007; 13(6): 385-388.
21.	Maeda K, Chung YS, Takatsuka S, et al. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma [J]. J Clin Oncol, 1995; 13(2): 477-481.
22.	Zhao J, Hu J, Cai J, et al. Vascular endothelial growth factor expression in serum of patients with hepatocellular carcinoma [J]. Chin Med J (Engl), 2003; 116(5): 772-776.
23.	Jinno K, Tanimizu M, Hyodo I, et al. Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma [J]. J Gastroenterol, 1998; 33(3): 376-382.
24.	赵文丽, 杨清绪, 武彤彤. 血管内皮生长因子及微血管密度在肝癌中的表达 [J]. 中国基层医药, 2006; 13(9): 1472-1473.
25.	Chen L, Lu P, Lu ZX, et al. Anticancer effect of PS-T on the experimental hepatocellular carcinoma [J]. Chin-Ger J Clin Onc, 2004; 3(1): 55-59.
26.	刘尚梅, 赵建军, 杨晓洁, 等. 肝细胞肝癌对机体细胞免疫的影响 [J]. 实用癌症杂志, 2005; 20(1): 68-70.
27.	Freise CE, Ferrell L, Liu T, et al. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma [J]. Transplantation, 1999; 67(4): 510-513.
28.	冯晓彬, 艾军华, 郑树国, 等. 槐耳颗粒对肝癌肝移植术后患者疗效的影响 [J]. 中华消化外科杂志, 2008; 7(6): 428-430.

1. He J, Gu D, Wu X, et al. Major causes of death among men and women in China[J]. N Engl J Med, 2005; 353(11): 1124-1134.
2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin, 2005; 55(2): 74-108.
3. Steinmüller T, Jonas S, Neuhaus P. Review article: liver transplantation for hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2003; 17 Suppl 2: 138-144.
4. Molmenti EP, Klintmalm GB. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry [J]. Liver Transpl, 2002; 8(9): 736-748.
5. 郑树森, 吴健. 肝移植治疗原发性肝癌的价值 [J]. 中国医学科学院学报, 2008; 30(4): 366-370.
6. 贺轶锋, 樊嘉, 周俭, 等. 影响肝癌肝移植预后的高危因素分析及诊治经验 [J]. 中华医学杂志, 2006; 86(18): 1232-1235.
7. Roayaie S, Schwartz JD, Sung MW, et al. Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis [J]. Liver Transpl, 2004; 10(4): 534-540.
8. 赵建军, 蔡建强, 毕新宇. 槐耳颗粒对原发性肝癌术后转移复发的影响 [J]. 中国综合临床, 2007; 23(3): 245-247.
9. Sobin LH, Wittekind CH. TNM classification of malignant tumors [M]. 6th ed. New York: Wiley-Liss, Inc, 2002: 272.
10. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis [J]. N Engl J Med, 1996; 334(11): 693-699.
11. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria [J]. Liver Transpl, 2002; 8(9): 765-774.
12. Li J, Yan LN, Yang J, et al. Indicators of prognosis after liver transplantation in Chinese hepatocellular carcinoma patients [J]. World J Gastroenterol, 2009; 15(33): 4170-4176.
13. 许戈良, 荚卫东, 马金良, 等. 槐耳清膏体外抑制血管生成的实验研究 [J]. 中国药理学通报, 2003; 19(12): 1410-1412.
14. 陈大兴, 陈孝平, 张万广. 槐耳清膏治疗肝癌的实验研究 [J]. 中国普通外科杂志, 2004; 13（8）: 578-582.
15. 王家顿, 谢大兴, 陈金明, 等. 抗癌药物诱导Molt-4细胞凋亡的周期时相性分析 [J]. 中国肿瘤, 2002; 11(9): 533-534.
16. 程若川, 汤礼贵, 兰丽琴. 槐耳浸膏诱导人直肠癌HR8348细胞凋亡的实验研究 [J]. 中国肿瘤, 2003; 12(2): 122-124.
17. 李立新, 叶胜龙, 王艳红, 等. 槐耳浸膏诱导肝癌细胞凋亡的实验研究 [J]. 中国临床医学, 2005; 12(6): 1152-1153.
18. 王建忠, 程若川. 槐耳的研制及临床应用 [J]. 井冈山医专学报, 2003; 10(1): 15-16.
19. 陈慎宝, 丁如宁. 槐耳菌质成分对小鼠免疫功能的影响 [J]. 食用菌学报, 1995; 2(1): 21-25.
20. 刘念, 耿小平, 朱立新, 等. 槐耳清膏体外逆转人肝细胞HepG2/ADM多药耐药性 [J].中华肝胆外科杂志, 2007; 13(6): 385-388.
21. Maeda K, Chung YS, Takatsuka S, et al. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma [J]. J Clin Oncol, 1995; 13(2): 477-481.
22. Zhao J, Hu J, Cai J, et al. Vascular endothelial growth factor expression in serum of patients with hepatocellular carcinoma [J]. Chin Med J (Engl), 2003; 116(5): 772-776.
23. Jinno K, Tanimizu M, Hyodo I, et al. Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma [J]. J Gastroenterol, 1998; 33(3): 376-382.
24. 赵文丽, 杨清绪, 武彤彤. 血管内皮生长因子及微血管密度在肝癌中的表达 [J]. 中国基层医药, 2006; 13(9): 1472-1473.
25. Chen L, Lu P, Lu ZX, et al. Anticancer effect of PS-T on the experimental hepatocellular carcinoma [J]. Chin-Ger J Clin Onc, 2004; 3(1): 55-59.
26. 刘尚梅, 赵建军, 杨晓洁, 等. 肝细胞肝癌对机体细胞免疫的影响 [J]. 实用癌症杂志, 2005; 20(1): 68-70.
27. Freise CE, Ferrell L, Liu T, et al. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma [J]. Transplantation, 1999; 67(4): 510-513.
28. 冯晓彬, 艾军华, 郑树国, 等. 槐耳颗粒对肝癌肝移植术后患者疗效的影响 [J]. 中华消化外科杂志, 2008; 7(6): 428-430.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Retrospective Cohort Study on Clinical Value of Huaier Granule in Postoperative Patients with Liver Transplantation for Hepatocellular Carcinoma

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