Does Screening for HCC in Cirrhotic Patients Reduce HCC-related Mortality?

 描述（由申请人提供）：肝细胞癌（HCC）是肝硬化最重要的临床并发症之一。许多供应商已采用超声检查和/或血清甲胎蛋白检测每6个月一次的方法对肝硬化患者进行HCC筛查。然而，缺乏高质量的数据来支持这种做法，而且在西方进行肝癌筛查的随机试验是极不可能的。我们提出了一项病例对照研究，以评估是否与USS或血清甲胎蛋白筛查肝癌与肝癌相关的死亡率降低在肝硬化患者。我们的具体目标是：1。确定腹部USS筛查HCC与HCC相关死亡率降低的相关程度。 2.确定血清AFP检测筛查HCC与HCC相关死亡率降低的相关程度。我们将使用国家VA企业数据仓库（CDW）确定2013日历年在该国任何VA机构接受治疗的所有退伍军人事务部（VA）肝硬化患者（n= 60，553），不包括不建议进行HCC筛查的患者。在这些患者中，我们将确定2013年死于HCC的患者，并随机选择450例。每个病例将与一个对照组相匹配，该对照组在其病例的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VA护理中。将根据种族、年龄、性别、肝硬化病因和肝硬化诊断年份进行匹配。将比较病例（N=450）和对照组（N=450）在诊断HCC（病例中）或其匹配对照组的等效索引日期前2、3或4年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HBV或HCV的抗病毒治疗、血清白蛋白、胆红素、血小板计数、糖尿病、肥胖、酒精滥用或依赖、Charlson-Deyo合并症指数、亚专科医生治疗和医疗机构的复杂程度。从CDW获得的电子数据将通过对病例/对照状态设盲的研究者进行的摘要病历审查进行补充，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由HCC引起。该研究有能力检测到与筛查相关的HCC相关死亡率降低大于30%（比值比<0.70），如果确实存在的话。

 DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is one of the most important clinical complications of cirrhosis. Screening for HCC in cirrhotic patients has been adopted by many providers using ultrasonography and/or serum alpha fetoprotein testing every 6 months. However, high quality data to support this practice are lacking and it is extremely unlikely that randomized trials of screening for HCC could ever be feasible in the West. We propose a case-control study to evaluate whether screening for HCC with USS or serum AFP is associated with reduced HCC-related mortality among cirrhotic patients. Our Specific Aims are to: 1. Determine the extent to which screening for HCC with abdominal USS is associated with reduced HCC- related mortality among cirrhotic patients. 2. Determine the extent to which screening for HCC with serum AFP testing is associated with reduced HCC-related mortality among cirrhotic patients. We will identify all Veterans Affairs (VA) patients with cirrhosis who received care in calendar year 2013 (n=60,553) in any VA facility in the country using the national VA Corporate Data Warehouse (CDW), excluding patients for whom HCC screening is not recommended. Among these patients, we will identify those who died of HCC in 2013 and randomly select 450 cases. Each case will be matched to one control who was not diagnosed with HCC as of the date of his case's HCC diagnosis, did not later die from HCC, and who was in VA care at the time his matched case died. Matching will be performed by race, age, gender, etiology of cirrhosis and year of diagnosis of cirrhosis. Cases (N=450) and controls (N=450) will be compared with respect to presence of abdominal ultrasound or serum AFP testing performed for screening purposes within 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 or HCV, serum albumin, bilirubin, platelet count, 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 review of abstracted medical records 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 study is powered to detect a reduction in HCC-related mortality associated with screening greater than 30% (odds ratio <0.70) if one truly exists.