A New Lab Based Algorithm for HCC Surveillance in Patients with Cirrhosis

一种基于实验室的新算法，用于肝硬化患者的 HCC 监测

• 批准号: 9210610
• 负责人: Hashem B El-Serag
• 金额: $ 63.67万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-12 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9210610
• 关键词: Address; Age; Alanine Transaminase; Algorithms; Aspartate Transaminase; Bilirubin; Biological Markers; Blood Platelets; Blood Tests; Calibration; California; Cancer Etiology; Cessation of life; Characteristics; Cirrhosis; Clinical; Communities; Data; Data Set; Derivation procedure; Detection; Discrimination; Early Diagnosis; Etiology; Evaluation; Fibrosis; Gastroenterology; Goals; Hepatitis C; Image; Infection; Inflammation; Liver; Liver Cirrhosis; Liver Function Tests; Liver diseases; Logistic Models; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Measurable; Medical Records; Modeling; Necrosis; Nested Case-Control Study; Output; Pathology; Patient risk; Patients; Performance; Periodicity; Platelet Count measurement; Predictive Value; Primary carcinoma of the liver cells; Probability; Process; Professional Organizations; Publications; Radiology Specialty; Registries; Risk; Serum; Severities; Standardization; Testing; Ultrasonography; United States; Update; Veterans; Work; X-Ray Computed Tomography; alpha-Fetoproteins; base; clinical practice; cohort; cost; curative treatments; follow-up; high risk; improved; predictive modeling; public health relevance; screening; tool; total measurement Bilirubin

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer related deaths in the United States. Survival is dismal except in a relatively small number of cases that are detected early and subjected to potentially curative treatment. Therefore, periodic surveillance for HCC has been recommended in patients with liver cirrhosis. Serum alpha-fetoprotein (AFP) has been extensively used as a marker for HCC detection, but its performance in the surveillance for HCC has been generally low. However, AFP test characteristics are influenced by severity and activity of liver disease that are partly reflected n serum levels of AST, ALT, bilirubin, platelets, etc. Incorporating some of these factors into an adjusted AFP-based algorithm may improve its predictive value in detecting HCC. Our preliminary predictive logistic model with AFP, age, ALT, and total bilirubin as continuous non-linear variables and interaction terms (AFP*ALT, AFP*bilirubin) found marked improvement in predicting HCC occurrence in the 6 months following an AFP test compared to AFP alone. This work has been accepted for publication in Gastroenterology. The proposed study will optimize the predictive utility of this promising yet preliminary algorithm by using an updated derivation dataset with longer follow up and more HCC cases, validate and refine the algorithm in two independent cohorts of HCV- and non HCV- related cirrhosis patients from the Department of Veterans Affairs (VA) and Kaiser Permanente Northern California (KPNC), and evaluate its clinical utility in detecting early HCC in comparison to liver ultrasound- and AFP -based screening at KPNC. Aim 1 (DERIVATION OF THE ADJUSTED AFP ALGORITHM): To maximize the predictive value of our preliminary AFP based model (adjusted AFP) in predicting the occurrence of HCC and estimate cutoffs for "positive or abnormal" results in a large derivation dataset of patients with cirrhosis and hepatitis C infection. Aim 2 (EXTERNAL VALIDATION): To test the use of our adjusted AFP model in predicting the risk of HCC in two external cohorts of patients with cirrhosis due to various etiologies. Aim 3 (TESTING OF CLINICAL UTILITY): To examine the clinical utility of the adjusted AFP algorithm in improving early HCC detection compared to standard serum AFP test with or without liver ultrasound screening (US) test. Given the wide availability of AFP tests, their high level of lab standardization, low cost, and the absence of promising and readily available new biomarkers, we believe that an adjusted AFP based algorithm may have an immediate utility and impact on clinical practice.

描述（由申请人提供）：肝细胞癌（HCC）是美国癌症相关死亡上升最快的原因。除了少数早期发现并接受潜在治愈性治疗的病例外，生存率很低。因此，建议肝硬化患者定期监测 HCC。血清甲胎蛋白（AFP）已被广泛用作HCC检测的标志物，但其在HCC监测中的表现普遍较低。然而，AFP 测试特征受到肝病严重程度和活动性的影响，部分反映在 AST、ALT、胆红素、血小板等血清水平上。将其中一些因素纳入调整后的基于 AFP 的算法中可能会提高其检测 HCC 的预测价值。我们以 AFP、年龄、ALT 和总胆红素作为连续非线性变量和交互项（AFP*ALT、AFP*胆红素）的初步预测逻辑模型发现，与单独使用 AFP 相比，在 AFP 测试后 6 个月内预测 HCC 发生率有显着改善。这项工作已被《胃肠病学》接受发表。 拟议的研究将通过使用具有更长随访时间和更多 HCC 病例的更新推导数据集来优化这一有前途但初步算法的预测效用，在来自退伍军人事务部 (VA) 和北加州凯撒医疗机构 (KPNC) 的两个独立的 HCV 和非 HCV 相关肝硬化患者队列中验证和完善该算法，并评估其算法 与 KPNC 基于肝脏超声和 AFP 的筛查相比，在检测早期 HCC 方面的临床实用性。 目标 1（调整后的 AFP 算法的推导）：最大化我们基于 AFP 的初步模型（调整后的 AFP）在预测 HCC 发生方面的预测价值，并估计肝硬化和丙型肝炎感染患者的大型推导数据集中“阳性或异常”结果的截止值。 目标 2（外部验证）：测试调整后的 AFP 模型在两个外部队列中预测 HCC 风险的用途，这些队列由不同病因引起的肝硬化患者组成。 目标 3（临床效用测试）：与标准血清 AFP 测试（有或没有肝脏超声筛查 (US) 测试）相比，检查调整后的 AFP 算法在改善早期 HCC 检测方面的临床效用。 鉴于 AFP 检测的广泛可用性、实验室标准化水平高、成本低以及缺乏有前途且易于获得的新生物标志物，我们相信基于调整后的 AFP 算法可能会对临床实践产生直接的效用和影响。