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

 描述（由申请人提供）： 肝细胞癌（HCC）是慢性B型肝炎病毒（HBV）感染的重要临床并发症之一。有人建议，HBV感染的患者应进行筛查肝癌与腹部超声检查，也可能血清甲胎蛋白（AFP）检测。然而，目前尚不清楚是否筛查HBV感染的患者与这两个测试降低HCC相关的死亡率。 我们的具体目标是：1。确定VA护理中HBV感染患者的腹部超声筛查HCC是否与降低HCC相关死亡率相关。 2.确定在VA护理中HBV感染患者中，血清AFP检测筛查HCC是否与降低HCC相关死亡率相关。我们将使用国家VA企业数据仓库（CDW）确定2003-2014年诊断为HBV感染（定义为血清HBV表面抗原[HBsAg]阳性）的所有VA患者，不包括HIV或丙型肝炎病毒（HCV）合并感染的患者和不建议进行HCC筛查的患者。在这些患者中，我们将确定死于HCC的患者（例）。每个病例将与2名对照匹配，这些对照在其病例的HCC诊断日期时未被诊断为HCC，后来未死于HCC，并且在其匹配病例死亡时正在接受VA护理。将根据人种、年龄、性别、是否存在肝硬化和HBV诊断年份进行匹配。将比较病例（N = 232-348）和对照组（N = 464-696）在诊断HCC（病例）前1、2、3或4年内或其匹配对照组的同等索引日期内是否存在腹部超声或血清AFP检测（用于筛选目的）。将进行条件多变量logistic回归，以调整可能与HCC死亡率和HCC筛查相关的其他潜在混杂因素（包括针对HBV的抗病毒治疗、HBV病毒载量、HBeAg状态、血清白蛋白、胆红素、血小板计数、APRI（AST与血小板比率指数）评分、糖尿病、肥胖、酒精滥用或依赖、Charlson-Deyo合并症指数、专科医生的治疗和医疗设施的复杂程度）。从CDW获得的电子数据将通过病例/对照状态设盲的研究者进行的病历摘要进行补充，以确认在关注期间是否进行了USS或血清AFP检测用于筛选，并确认病例中的死亡是由HCC引起的。 VHA代表了一个理想的（可能是唯一的）设置在美国的拟议研究，由于存在一个国家的电子医疗数据库延伸到1999年，电子医疗记录的普遍使用，能够访问电子医疗记录的国家和大量的HBV感染的患者谁接受护理几乎完全在VHA医疗保健系统。这项研究是一项随机对照试验的最佳方法，以确定在美国HBV感染患者中，HCC筛查是否与降低HCC相关死亡率相关。

 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.