- 學位論文
Sorafenib使用於台灣B型或C型肝炎相關肝癌
Sorafenib use in hepatitis B virus or hepatitis C virus related hepatocellular carcinoma in Taiwan
摘要
【目標】 現行在治療肝癌(巴塞隆納肝癌分期C)患者被核准的治療為Sorafenib，而全球分布來看B型肝炎又常常是造成肝癌的主要原因，特別是在台灣B型肝炎又是居多，然而有需多研究指出Sorafenib在治療C型肝炎的臨床效益優於B型肝炎，故此篇研究目標在於比較在台灣B型肝炎或C型肝炎相關肝癌使用蕾莎瓦有無差異。 【方法】 收錄西元2012年8月到2016年12月申請Sorafenib健保治療的晚期肝癌病人共575人。依照台灣國民健康保險（NHI）所登記標準為巴塞隆納肝癌分期C期肝癌，且有肉眼血管侵犯（VI）或肝外轉移（Mets）且Child-Pugh（CP）A級患者。用Sorafenib治療期間，使用影像學評估(CT or MRI)每隔2個月進行一次 評估標準為修正版實體腫瘤的反應評估標準(mRECIST)。 患者的治療直到腫瘤進展（TP）或肝功能惡化（LD）且不可逆CP評分增加≥2的患者，或確定不允許使用台灣國民健康保險所提供Sorafenib。且患者在使用Sorafenib時可同時接受手術、局部電燒、栓塞治療。且我們會使用Propensity scoring來消除B型和C型肝炎兩組病人基準線上的各種差異。最後會比較兩組病人overall survival (OS) 和progression free survival (PFS)的表現。 【結果】 B型肝炎合併肝癌患者共277人(62.4%)、C型肝炎合併肝癌患者共167人(37.6%)，兩組患者使用Sorafenib的治療時間都是4個月。無疾病惡化存活期在B肝組為2.1個月、C肝組為2.1個月(p=0.582)，在整體存活期分別是8.8個月比上8.8個月(p=0.623)，結果顯示並無顯著差異。且在經過年齡、性別、肝功能、腫瘤大小、腫瘤型態的配對後，無疾病惡化存活期在B肝組為2個月、C肝組為2.1個月(p=0.374)，在整體存活期分別是10.5個月比上9.6個月(p=0.746)，依然無顯著差異。 【總結】 本研究的初步結果與一開始的假設相反，即便經過傾向分配後還是得到B型肝炎共病肝癌組別的整體存活期與無疾病惡化存活期與C型肝炎共病肝癌組別相比並於統計上顯著的差異。可能因為我國在肝病健保給付完整的緣故，才有將近七成的晚期肝癌患者可以同時接受抗B型肝炎病毒藥物的治療。合併使用sorafenib與抗B型肝炎病毒藥物在B型肝炎共病肝癌患者，似乎可以明顯改善患者的整體存活期。
並列摘要
【Background/Aims】 Sorafenib is the approved treatment option in the patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage C. Hepatitis B virus (HBV) is the main etiology of HCC worldwide, especially in Taiwan. Some studies reported that hepatitis C virus (HCV) related HCC had a better outcome than HBV related HCC in sorafenib use, but it is still a controversy. This study aimed to evaluate the difference of sorafenib use between HBV related HCC and HCV related HCC in Taiwan 【Methods】 From Aug 2012 to Dec 2016, 575 consecutive advanced HCC patients received sorafenib under NHI in our hospital. The reimbursement criteria of Taiwan National Health Insurance (NHI) were BCLC stage C HCC with macroscopic vascular invasion (MVI) or extrahepatic metastasis (EHM) Child–Pugh (CP) class A. Radiologic assessment was performed at a 2-month interval using modified Response Evaluation Criteria in Solid Tumors. Disallowance for using sorafenib continually under NHITumor progression (TP) or Liver function deterioration (LD) with irreversible CP score increase≥2. Combined treatment was defined as patients received resection, local ablation or transcatheter arterial chemoembolization with sorafenib. Propensity scoring was also used for control of selection bias and performed using binary logistic regression to generate a propensity score for each HBV or HCV patients. After amending confounding factors, overall survival (OS) and progression free survival (PFS) analyses were repeated. 【Results】 There were 277 (62.4%) HBV-HCC patients and 167 (37.6%) HCV-HCC patients. The interval of sorafenib-use was 4 months for HBV patients for HCV patients, respectively. Progression free survival (PFS) of HBV patients and HCV patients (2.1 months vs 2.1 months, p=0.582 ) as well as overall survival (OS) (8.8 months vs 8.8 months, p=0.623) were not different. Even after propensity score matching of confounding factors including age, sex, AST, ALT, APRI, FIB-4, tumor size, and tumor pattern, PFS and OS of HBV-HCC patients and HCV-HCC patients were still not different (2 months vs 2.1 months, p=0.374 in PFS;10.5 months vs 9.6 months in OS, p=0.746 ). 【Conclusion】 In our study, we get a difference outcome to other study. Even after matching HBV or HCV related HCC patients in BCLC stage C still have not difference in OS. We think National Health Insurance is the major reason leading to this result. Combining Anti-viral drug with sorafenib perhaps can improve OS in HCC patients in BCLC stage C patients.