核苷（酸）IDE类似物治疗降低肝癌的风险

StephenW

                                                                                                                                                                    

Association of Nucleos(t)ide Analogue Therapy With Reduced Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B-A Nationwide Cohort Study
	Download the PDF here         "In conclusion, nucleos(t)ide analogue use is associated with reduced risk of HCC in CHB patients. Age, sex, liver cirrhosis, and diabetes mellitus modify this association. More studies are needed to explore the wider use of nucleos(t)ide analogues for prolonged periods to decrease the incidences of HCC.Without controlling for other factors, nucleos(t)ide analogue treatment was associated with reduced risk of HCC development (hazard ratio [HR] = 0.34; 95% CI: 0.32-0.37; P < .001)[63% lower risk] ......After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). ....The treated cohort had a significantly lower incidence of HCC (n = 992 [4.6%]) when compared with the untreated cohort (n = 4454 [20.6%])" "For noncirrhotic CHB patients, mean annual incidences of HCC were 0.68% and 2.97% for the treated and the untreated cohorts, respectively. Adjusted HR was 0.25 for the use of nucleos(t)ide analogues.......For cirrhotic CHB patients, the mean annual incidences of HCC in the present study were 3.90% and 4.94% for treated and untreated cohorts, respectively. The adjusted HR was 0.72 for the use of nucleos(t)ide analogue" " ......The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001)......Competing mortality (death before development of HCC) was significantly lower in the treated cohort (n = 1036 [4.8%]) than in the untreated cohort (n = 2256 [11.8%]). Overall mortality in the treated cohort (n = 1406 [6.5%]) was also significantly lower than in the untreated cohort (n = 4778 [22.1%])." "Older age, male sex, and liver cirrhosis (HR 1.92; highest risk) were found to be risk factors for increased HCC risk. Patients with comorbidities including liver decompensation, hypertension, chronic obstructive pulmonary disease, acute coronary syndrome, and cerebral vascular diseases were found to be associated with reduced risk of HCC due to higher competing mortality. Use of statin and use of nonsteroidal anti-inflammatory drugs or aspirin were associated with significantly lower risk of HCC in CHB patients (Table 2)." Figure 2: Cumulative incidences of HCC after adjustment for competing mortality. Calculation and comparison of cumulative incidences in competing risk data ratios were conducted using modified Kaplan-Meier method and Gray's method. Patients who developed HCC during the first 3 months were excluded. Untreated, CHB patients not receiving nucleos(t)ide analogues; Treated, CHB patients receiving nucleos(t)ide analogues. ".....reimbursement for nucleos(t)ide analogues requires twice-elevated aminotransferase and higher HBV DNA levels (>2000 IU/mL), and reimbursement for hepatoprotective agents (control group) requires only elevated aminotransferase level (ALT ≥1x), the higher baseline HBV DNA levels and ALT levels in the treated cohort might have led to a more conservative estimation of the protective effect of nucleos(t)ide analogues." ------------------- Association of Nucleos(t)ide Analogue Therapy With Reduced Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B-A Nationwide Cohort Study Gastroenterology July 2014 Chun-Ying Wu,1,2,3,4 Jaw-Town Lin,5,6,7 Hsiu J. Ho,5 Chien-Wei Su,2,8,9 Teng-Yu Lee,1,3Shen-Yung Wang,8 Chuhui Wu,8 and Jaw-Ching Wu8,101Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; 2Faculty of Medicine, School ofMedicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Public Health and Graduate Institute of ClinicalMedicine, China Medical University, Taichung, Taiwan; 4Department of Life Sciences, National Chung-Hsing University,Taichung, Taiwan; 5School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; 6Department of Internal Medicine,E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 7Institute of Population Health Sciences, National Health ResearchInstitutes, Miaoli, Taiwan; 8Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei,Taiwan; 9Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; and 10Translational Research Division,Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan

StephenW

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“总之，核苷（酸）类似物IDE的使用与肝癌的慢性乙型肝炎患者的风险降低有关。年龄，性别，肝硬化和糖尿病修改此关联。需要更多的研究来探索更广阔的应用核苷（t）的。IDE类似物长时间降低肝癌的发生率没有控制其他因素，核苷（酸）类似物IDE治疗肝癌的发展降低风险（风险比[HR]为0.34; 95％CI：0.32-0.37; P <0.001）降低63％的风险] ......调整竞争死亡率和其他的干扰因素，核苷后（T）IDE类似物治疗肝癌的风险降低相关联，与0.37调整后的危险比（ 95％CI，0.34-0.39，P<0.001）....的处理队列中有肝癌（N=992[4.6％]）时，与未经处理的队列比较（N=4454[20.6％的显著发病率较低]）“

“对于肝硬化的慢性乙肝患者，肝癌平均每年发生率分别为0.68％及经处理和未经处理的同伙，分别为2.97％，调整后的HR为0.25，使用核苷（酸）类似物.......对于肝硬化慢性乙肝患者，肝癌在本研究中，平均每年发生率分别为3.90％和处理和未处理的同伙4.94％，分别调整后的HR为0.72对于使用核苷（酸）类似物IDE“

“......经过处理的队列有显著低7年发病率肝癌（7.32％，95％信心区间[CI]为6.77％-7.87％）比对照组（22.7％，95％CI，22.1％ -23.3％，P<0.001）......竞争的死亡率（死亡肝癌的发展前）是在处理队列显著下（N=1036[4.8％]），比未经处理的队列（N=2256[11.8％]），在处理队列（N=1406[6.5％]总死亡率）也比未治疗人群（N=4778[22.1％]）显著低。“

“年龄大，男性，肝硬化（HR1.92，最高的风险）被认为是危险因素增加肝癌风险的患者合并症，包括肝功能失代偿，高血压，慢性阻塞性肺疾病，急性冠脉综合征，脑血管疾病。被发现与肝癌的风险降低由于较高的竞争死亡率。使用他汀类药物和使用非甾体类抗炎药或阿司匹林与肝癌的慢性乙型肝炎患者（表2）显著降低风险有关联的。“

图2：肝癌调整死亡率竞争后累积发生率。计算及竞争风险数据比累计发生率的比较采用改良Kaplan-Meier法和灰色的方法进行。谁在头3个月开发的肝癌患者被排除在外。不及时治疗，慢性乙肝患者没有接受核苷（酸）类似物;治疗，慢性乙型肝炎患者接受核苷（酸）类似物。


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“.....报销核苷（酸）类似物，需要两次转氨酶升高和较高的HBV DNA水平（>2000 IU/毫升），并偿还保肝药物（对照组）仅需要转氨酶水平（ALT≥1x ），较高的基线HBV DNA水平和ALT水平在处理的队列可能导致的核苷（酸）类似物的保护作用的更保守的估计。“

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核苷（酸）IDE类似物治疗协会肝癌患者的风险降低慢性肝炎BA全国队列研究

消化内科
2014年7月

春英巫，1,2,3,4林肇堂，5,6,7修J.豪，5千千韦素，2,8,9腾宇李1,3沉容王8 Chuhui武，8和消化内科，台中荣民总医院，台中，台鄂晴Wu8,101区; 2Faculty医学，医药，国立阳明大学，台北，台湾的学校; 3Department临床医学院中国医科大学公共卫生与研究所，台中，台湾; 4Department生命科学院，国立中兴大学，台中，台湾; 5School药，辅仁大学，台北，台湾; 6Department内科，义大医院/义守大学，高雄，台湾; 7Institute群体健康科学，国家卫生研究院，台湾苗栗; 8Institute临床医学和基因组研究中心，国立阳明大学，台北，台湾; 9Division消化内科，台北荣民总医院，台北，台湾;和10Translational研究部医学研究部，台北荣民总医院，台北，台湾