改善肝癌预后 关注背景治疗课件

1、关注背景治疗 改善肝癌预后目录 肝炎/肝硬化是肝细胞癌的重要危险因素 合并肝炎/肝硬化对肝细胞癌预后的影响 肝细胞癌合并肝炎/肝硬化的治疗The relationship of Hepatitis/Cirrhosis/HCCThe influence of coexisting Hepatitis/Cirrhosis on HCC OutcomeThe principle of HCC patients with Hepatitis/Cirrhosis management肝炎/肝硬化是肝细胞癌的重要危险因素Part 1原发性肝细胞癌 (HCC) 是全球第七大常见癌症 全球每年报道600 00

2、0例HCC患者，其中亚洲约占78%Hepatocellular carcinoma (HCC) is the seventh most common cancer and third leading cause of cancer-related death in the world according to theNat. Rev. Gastroenterol. Hepatol. 7, 448458 (2010); published online 13 July 2010亚洲欧洲大洋洲非洲拉丁美洲和地中海区域南美GloboCan 2008 report.Hepatocellular car

3、cinoma (HCC) is the 7th most common cancerAsian countries account for nearly 78% of the roughly 600 000 cases of hepatocellular carcinoma (HCC) reported globally each year.肝病三部曲肝细胞癌肝炎(主要为病毒性)肝硬化15-20%在5年内发展至肝硬化患者的HCC年发病率约为3-6%Med Clin N Am 89 (2005) 371389N Engl J Med. 1997 Dec 11;337(24):1733-45HCC

4、 may develop at an annual incidence of 3-6% in cirrhosis肝炎类型概述肝炎类型抗原相应的抗体病毒类型AHAVAnti-HAVRNABHBsAgHBcAgHbeAgAnti-HBsAnti-HBcAnti-HBeDNACHCAgAnti-HCVRNADHDAgAnti-HDV缺陷RNAEHEAgAnti-HEVRNAGHGAgNARNA其他SystemicRegional自身免疫性肝炎病毒性肝炎HAVHBVHCVHDVHEVHGV酒精性肝炎药物性肝炎肝炎9.74% in 19927.18% in 20062008年，病毒性肝炎仍然是中国第一位

5、的传染病，年发病数140.7万全国每年死于与乙肝相关肝病近30万例中国乙肝病毒感染现状Maps were generated using incidence rates of liver cancer from GLOBOCAN 2002全球78%的HCC归因于HBV/HCV感染Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer world

6、wide. J Hepatol 2006;45:529-538.57% of cirrhosis was attributable to either HBV (30%) or HCV (27%) and 78% of HCC was attributable to HBV (53%) or HCV (25%).The estimated fractions of cirrhosis attributable to HBV infection ranged from 5% (AMR-A) to 57% (WPR-B) (Table 4, Fig. 1). The fractions of ci

7、rrhosis attributable to HCV infection ranged from 16% (AFRD/E) to 62% (WPR-A). The attributable fractions of HCC due to HBV or HCV ranged from 16% (AMRA) to 65% (WPR-B) and from 13% (EMR-B) to 66% (WPR-A), respectively. The two viruses together accounted for 50% of HCC in all of the regions; this wa

8、s also true for cirrhosis in 8 of 11 regions. Globally, we estimated that approximately 57% of cirrhosis was due to either HBV (30%) or HCV (27%) (Table 4). For HCC, approximately three-quarters (78%) was attributable to HBV (53%) or HCV (25%).Hepatol 2006;45:529-538.乙肝/丙肝病毒对原发性肝细胞癌及肝硬化的影响比例The cont

9、ributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwideHBV是亚洲国家HCC的主要致病因素慢性HBV感染东北及东南亚国家的主要致病因素中国，香港，印度尼西亚，朝鲜及台湾。全世界共3.6亿HBV携带者，其中亚洲HBV携带者占绝大多数亚洲HBV感染的患病率差异较大，日本、新加坡及泰国为1-5%，印度尼西亚和中国北部为6-10%，台湾、中国南部、朝鲜及菲律宾超过10%。日本和台湾慢性HCV感染是HCC发生的重要因素。预计丙肝病毒将成为

10、亚洲肝细胞癌增长的主要推动因素，不同肝炎病毒之间的协同作用以及环境等因素将共同影响HCC的发病率。Lancet Oncol 2009; 10: 111118亚洲肿瘤峰会2010亚洲肝细胞癌治疗共识指出：慢性HBV感染是东北及东南亚国家的主要致病因素，包括中国，香港，印度尼西亚，朝鲜及台湾。全世界3.6亿携带者中亚洲HBV携带者占绝大多数The high prevalence of chronic HBV carriers in Asia constitutes the majority of the 360 million carriers worldwide. 亚洲，HBV感染的患病率有很大

11、差异，日本、新加坡及泰国为1-5%，印度尼西亚和中国北部为6-10%，而台湾、中国南部、朝鲜及菲律宾则超过10%。在日本和台湾，慢性HCV感染是HCC发生的重要因素. HCV infection is expected to increase as an aetiological factor associated with HCC in Asia. The synergistic interactions of interviral, viral, and environmental risk factors complicate matters.亚洲国家HCC的治疗: consensus

12、statement from the Asian Oncology Summit 2009In Asia, the main etiological factor of HCC is hepatitis B virus The main aetiological factor is chronic hepatitis B virus (HBV) infection in northeast and southeast Asia, including China, Hong Kong, Indonesia, Korea, and Taiwan. The high prevalence of ch

13、ronic HBV carriers in Asia constitutes the majority of the 360 million carriers worldwide. In Asia, there is wide variation in the prevalence of HBV infection; prevalence is 15% in Japan, Singapore, and Thailand, 610% in Indonesia and northern China, and higher than 10% in Taiwan, southern China, Ko

14、rea, and the Philippines.Chronic hepatitis C virus (HCV) infection also has a substantial role in the development of HCC in Japan and Taiwan. HCV infection is expected to increase as an aetiological factor associated with HCC in Asia. The synergistic interactions of interviral, viral, and environmen

15、tal risk factors complicate matters.HBV及其相关性肝硬化患者HCC发病率根据不同地区及临床表现分层统计的乙肝患者HCC发病率横断面研究汇总GASTROENTEROLOGY 2004;127:S35S50HCC incidence in Hepatitis B and its related cirrhosisOverall Hepatocellular Carcinoma Incidence Rates in Longitudinal Studies of Patients With Chronic Hepatitis B Infection Accord

16、ing to Clinical Setting and Geographic Area临床表现地区研究数量患者人数平均随访期HCC发病率95%CI无症状乙肝携带者北美2180416年0.10.07-0.14台湾/中国大陆4188698年0.70.51-0.70日本15137.30.20.08-0.39非活动期携带者欧洲3410160.020-0.04台湾118980.20-0.42慢性乙肝欧洲64715.90.10-0.27台湾24614.01.00.36-1.56日本27375.10.80.46-1.06肝硬化代偿期欧洲64015.82.21.94-4.55台湾/新加坡32784.33.21

17、.94-4.55日本23065.84.33.40-5.25HBV/HCV相关性肝硬化患者HCC发病率约为3%/年N Engl J Med 1991;325:675-680.无肿瘤生存率（%）0612182430364248100806040200HCC : 3%3%2%意大利肝硬化患者调查，n=447，肝硬化代偿期，每3-12个月进行血清AFP及腹部超声检查 3% compensated cirrhosis with HBV/HCV develop HCC per yearPART 1 小结HBVHCV肝硬化肝癌肝癌的发生是一个多因素、多阶段的发展过程， 其中HBV、HCV慢性感染与肝癌的发生

18、关系最为密切。大多数肝癌患者多由肝炎肝硬化发展而来肝硬化是大多数肝癌的共同特征，目前公认再生结节是恶性克隆形成和增殖位点Med Clin N Am 89 (2005) 371389合并肝炎/肝硬化对HCC预后的影响Part 2概述HCC合并HBeAg+肝炎HBV 高负荷肝硬化肝功能储备低影响HCC预后减少生存期增加复发风险持续高HBV负荷HCC术后OS的独立危险因素P=0.018OS(%)01224364860728496108Journal of Gastroenterology and Hepatology. Jun 2010. Published on line first.n=188,

19、 HBV相关性HCC, 已接受手术切除治疗，平均随访48.5个月010080604020Figure 3. Overall survival in the 115 patients surviving more than 1 year without recurrence after resection. There is a significantly longer survival in the sustained low viremia group than the other groups (log-rank test, P = 0.018). Sustained high virem

20、ia group (solid line), patients with sustained HBV DNA levels 105 copies/ml during the follow-up; sustained low viremia group (dotted line), patients with sustained HBV DNA levels 104 copies/ml; fluctuating HBV DNA group (dashed line), the remaining patients.持续低病毒血症HBV DNA波动持续高病毒血症随访时间（月）HCV亦是HCC术后肝

21、内复发的重要危险因素 Eur J Surg Oncol. 2003 Apr;29(3):266-71.肝内复发累积概率（%）肝切除术后时间020406080100012345678910NBNC(N=24)B-viral(N=32)C-viral (N=55)P=0.0306n=111，HCC术后，分为HCV/HBV/无HV 3组HCV is significant risk factor for intrahepatic recurrence after HCC resection 肝功能低下的HCV相关性HCC患者RFA治疗后远处复发率高Months after RFAAliment Ph

22、armacol Ther. 2008 Jun;27(12):1253-60n=117，HCV，非晚期肝癌，行导管射频消融（RFA）治疗P=0.003远处复发率率(%)0102030405060010080604020Child AChild BDistant recurrence is at high rates in LOW LIVER FUNCTION RESERVE HCV related patients after RFADistant recurrence(%)合并肝硬化的HCC患者死亡和复发风险显著增加024681020406080100复发率(%)024681020406080

23、100OS(%)肝切除术后时间（年）肝切除术后时间（年）P 0 .03P 0 .0001P 250/mm3需起始经验性抗生素治疗A,II初始经验性抗生素治疗的建议头孢噻肟; 最低剂量 2 g/12 h, 至少使用5 dA,I其他可用抗生素: 头孢唑肟，头孢尼西，头孢三嗪，头孢他啶，阿莫西林/克拉维酸，常规剂量AE, II对非复杂性SBP且未使用喹诺酮预防性治疗的患者可选用氧氟沙星口服E,I已使用喹诺酮的患者，可选用头孢噻肟A,III对内酰胺过敏的患者可选用喹诺酮A,IV应避免使用氨基糖甙类抗生素A,IJournal of Hepatology 2000; 32: 142-153A：有生存获益；E：医疗保健花费影响I：至少有一项合理的随机对照研究作为证据; II：至少有下列一项依据：设计良好的非随机临床试验；队列或病例对照研究；设计良好的meta分析; III：依据临床经验；观察性研究；专家共识; IV：无分级自发性细菌性腹膜炎静脉白蛋白联合抗生素降低肾损伤风险优于单用抗生素N Engl J Med 1999;341:403-9.n=126，肝硬化并发自发性细菌性腹膜炎（SBP），随机予头孢噻肟（cefo