Does screening for HCC reduce HCC-related mortality in HBV-infected Veterans?

 描述(由申请人提供)： 肝细胞癌是慢性乙型肝炎病毒感染最重要的临床并发症之一。有人建议，乙肝病毒感染的患者应接受腹部超声筛查肝癌，可能还应进行血清甲胎蛋白(AFP)检测。然而，目前尚不清楚使用这两种检测方法筛查乙肝病毒感染患者是否会降低与肝癌相关的死亡率。我们的具体目标是：1.确定在VA护理中使用腹部超声筛查肝癌是否与降低乙肝病毒感染患者的肝癌相关死亡率有关。2.确定通过血清AFP检测筛查肝癌是否与VA护理中乙肝病毒感染患者的肝癌相关死亡率降低有关。我们将使用国家退伍军人事务部数据仓库(CDW)识别2003-2014年间所有确诊为乙肝病毒感染(定义为血清乙肝病毒表面抗原[HBs Ag]阳性)的退伍军人管理局患者，不包括艾滋病毒或丙型肝炎病毒(HCV)混合感染的患者和不建议进行肝细胞癌筛查的患者。在这些患者中，我们将确定哪些人死于肝癌(病例)。每个病例将与2名对照组配对，他们在病例确诊之日尚未被诊断出患有肝癌，后来没有死于肝癌，并且在匹配的病例死亡时正在接受VA护理。配对将根据种族、年龄、性别、有无肝硬变和诊断乙肝病毒的年份进行。对病例(N˜232-348)和对照组(N˜464-696)在诊断为肝细胞癌前1年、2年、3年或4年内(病例中)或与之匹配的对照组中同等指标日期前1年、2年、3年或4年内进行的腹部超声或血清甲胎蛋白筛查进行比较。应用条件多因素Logistic回归分析调整可能与肝癌死亡率和肝癌筛查(包括抗病毒治疗、乙肝病毒载量、HBeAg状态、血清白蛋白、胆红素、血小板计数、APRI评分、糖尿病、肥胖、酗酒或依赖、Charlson-Deyo共病指数、专科医生的治疗和医疗设施的复杂程度)相关的其他潜在混杂因素。从CDW获得的电子数据将由对病例/控制状况视而不见的调查人员执行的医疗图表摘要补充，以确认是否在感兴趣的期间进行了USS或血清AFP检测以进行筛查，并确认病例中的死亡是由肝癌引起的。VHA是美国开展这项拟议研究的理想(也可能是唯一的)环境，这是因为VHA存在一个可持续到1999年的国家电子医疗数据储存库，电子医疗记录的普遍使用，全国范围内访问电子医疗记录的能力，以及大量几乎完全在VHA医疗系统内接受护理的乙肝病毒感染患者。这项拟议的研究代表了缺乏随机对照试验的最佳方法，以确定筛查肝细胞癌是否与降低美国乙肝病毒感染患者的肝细胞癌相关死亡率有关。

 DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is one of the most important clinical complications of chronic hepatitis B virus (HBV) infection. It has been suggested that HBV-infected patients should undergo screening for HCC with abdominal ultrasonography and possibly also serum alpha fetoprotein (AFP) testing. However, it is unclear if screening HBV-infected patients with these two tests reduces HCC-related mortality. Our Specific Aims are to: 1. Determine whether screening for HCC with abdominal ultrasonography is associated with reduced HCC-related mortality among HBV-infected patients in VA care. 2. Determine whether screening for HCC with serum AFP testing is associated with reduced HCC-related mortality among HBV-infected patients in VA care. We will identify all VA patients with diagnosed HBV infection (defined as positive serum HBV surface antigen [HBsAg]) from 2003-2014 using the national VA Corporate Data Warehouse (CDW), excluding patients with HIV or hepatitis C virus (HCV) co-infection and patients for whom HCC screening is not recommended. Among these patients, we will identify those who died of HCC (cases). Each case will be matched to 2 controls who were not diagnosed with HCC as of the date of their case's HCC diagnosis, did not later die from HCC, and who were in VA care at the time their matched case died. Matching will be performed by race, age, gender, presence/absence of cirrhosis and year of diagnosis of HBV. Cases (N˜232-348) and controls (N˜464-696) will be compared with respect to presence of abdominal ultrasound or serum AFP testing performed for screening purposes within 1, 2, 3, or 4 years prior to the diagnosis of HCC (in the cases) or the equivalent index date in their matched controls. Conditional multivariate logistic regression will be performed to adjust for additional potential confounders that may be associated with both mortality from HCC and screening for HCC (including antiviral treatment for HBV, HBV viral load, HBeAg status, serum albumin, bilirubin, platelet count, APRI (AST to platelet ratio index) score, diabetes, obesity, alcohol abuse or dependence, Charlson-Deyo comorbidity index, treatment by subspecialists and complexity level of medical facility). Electronic data obtained from the CDW will be supplemented by medical chart abstraction performed by the investigators blinded as to case/control status to confirm whether USS or serum AFP testing during the period of interest was performed for screening or not and to confirm that deaths were caused by HCC in the cases. The VHA represents an ideal (and possibly the only) setting in the United States for the proposed study, due to the presence of a national repository of electronic medical data extending to 1999, the universal use of electronic medical records, the ability to access electronic medical records nationally and the large number of HBV-infected patients who receive care almost exclusively within the VHA healthcare system. The proposed study represents the best methodology short of a randomized controlled trial to determine whether screening for HCC is associated with reduced HCC-related mortality in HBV-infected patients in the United States.