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）是美国与癌症相关死亡的最快增长。生存是令人沮丧的，除了在相对较少的病例中被检测到并经过潜在的治疗方法。因此，在肝硬化患者中建议对HCC进行周期性监测。血清α-毒素（AFP）已被广泛用作HCC检测的标记，但其在HCC监视中的性能通常很低。但是，AFP测试特征受肝病的严重程度和活性的影响，部分反映了N AST，ALT，ALT，胆红素，血小板等的N血清水平。将其中一些因素纳入基于AFP的调整后的算法可能会提高其预测价值检测HCC。我们的初步预测逻辑模型具有AFP，年龄，ALT和总胆红素作为连续的非线性变量和相互作用项（AFP*ALT，AFP*胆红素），发现在AFP测试后6个月的HCC发生在AFP测试后的HCC发生方面有明显改善一个人一个人。这项工作已被接受用于胃肠病学的发表。 拟议的研究将通过使用更新的衍生数据集和更长的后续案例和更多的HCC病例，验证和完善来自HCV和非HCV相关肝硬化患者的两个独立人群中的算法，从而优化这种有希望而又初步的算法的预测效用。退伍军人事务部（VA）和Kaiser Permanente North California（KPNC），并评估其在KPNC上基于肝脏超声和AFP的筛查相比，在检测早期HCC方面的临床实用性。 AIM 1（调整后的AFP算法的推导）：为了最大程度地提高基于AFP的初步模型（调整后的AFP）的预测值，以预测HCC的发生并估算“正或异常”的临界值，从而导致大量衍生患者数据集的大量衍生数据。肝硬化和丙型肝炎感染。 AIM 2（外部验证）：测试我们调整后的AFP模型的使用，以预测两名由于各种病因而导致的两名外部肝硬化患者中HCC的风险。 AIM 3（临床实用程序的测试）：与标准血清AFP测试相比，调整后的AFP算法在改善早期HCC检测方面的临床实用性（有或没有肝脏超声检查（US）测试）。 鉴于AFP测试的广泛可用性，其高水平的实验室标准化，低成本以及缺乏有希望且容易获得的新生物标志物，我们认为基于调整后的AFP算法可能会立即具有效用和对临床实践的影响。