Improving the Diagnosis and Fibrosis Risk Assessment of Nonalcoholic Fatty Liver Disease in Primary Care Patients with Abnormal Liver Chemistries

改善肝脏化学异常的初级保健患者非酒精性脂肪肝的诊断和纤维化风险评估

• 批准号: 10616810
• 负责人: Andrew David Schreiner
• 金额: $ 11.33万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10616810
• 关键词: Abdomen; Acute; Address; Adult; Age Years; Alcoholic Liver Diseases; Alcohols; Biometry; Cardiovascular system; Cause of Death; Cessation of life; Chemistry; Chronic; Cirrhosis; Clinical; Code; Communities; Data; Death Rate; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic Errors; Disease; Disease Management; Disease Outcome; Disease model; Early Diagnosis; Electronic Health Record; Elements; Endocrinology; Epidemiology; Evaluation; Fatty Liver; Fibrosis; Future; Goals; Health Services Research; Hepatitis B; Hepatitis C; Hepatitis C virus; Hepatology; High Prevalence; Hypertension; Image; K-Series Research Career Programs; Link; Liver; Liver Failure; Liver diseases; Measurement; Measures; Mediating; Modeling; Obesity; Outcome; Patients; Performance; Portal Hypertension; Prevalence; Primary Care; Primary carcinoma of the liver cells; Recording of previous events; Research; Research Personnel; Risk; Risk Assessment; Risk Factors; Sampling; Severities; Signal Transduction; Signs and Symptoms; Specificity; Steatohepatitis; Step Tests; Technology; Testing; Time; Training; Transaminases; Treatment Efficacy; Viral hepatitis; Work; alcohol exposure; chronic liver disease; cohort; diagnostic strategy; disease diagnosis; disease diagnostic; effective therapy; effectiveness evaluation; elastography; end stage liver disease; follow-up; health economics; high risk; improved; indexing; liver stiffness; medical specialties; mortality; non-alcoholic fatty liver disease; predictive modeling; primary care patient; primary care setting; radiological imaging; response; simple steatosis; support tools; tertiary care; ultrasound; vibration

Abstract Improving the Diagnosis and Fibrosis Risk Assessment of Nonalcoholic Fatty Liver Disease in Primary Care Patients with Abnormal Liver Chemistries. Chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), and viral hepatitis, often go undetected in their early stages, a diagnostic delay directly harmful to patients.1,2 Pervasive diagnostic error fuels the climbing toll of chronic and end-stage liver disease, despite the increasing availability and efficacy of therapeutic options.3 Liver chemistry elevations may signal chronic liver disease, and systematic responses to these abnormalities can lead to earlier disease recognition and delivery of effective treatment.4-11 Currently, responses to abnormal liver tests in primary care lack consistency and contribute to diagnostic error.11-17 Our K23 work found nearly 12% of patients with abnormal liver tests lacked repeat assessment, and only 16% of patients with consecutive liver test abnormalities received timely viral hepatitis C testing.14,16 These limited and inconsistent evaluations challenge our ability to develop models linking patient-level variables to liver disease diagnoses. Diagnosing NAFLD poses unique challenges, as the diagnosis requires a negative alcohol exposure history, a comprehensive ruling out of other liver conditions, and/or abdominal imaging, elements inaccessible or absent in electronic health records.11,18 Despite primary care-based risk factors including obesity, hypertension, and diabetes, NAFLD remains underdiagnosed in this setting.18-22 Our K23 work highlights the severity of this underdiagnosis, as only 31% of patients with radiographic evidence of hepatic steatosis and no known (non- NAFLD) chronic liver disease (n=767) ever received a diagnosis code for NAFLD. Beyond diagnosis, NAFLD management in primary care requires fibrosis risk assessment because the presence of advanced fibrosis is the best indicator of liver-related, cardiovascular, and overall mortality in these patients.23- 25 Current fibrosis risk assessments begin with non-invasive risk scores, including the Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis score (NFS), to identify patients most likely to benefit from hepatology referral.6,18,26-28 FIB-4 and NFS were developed and tested in specialty and tertiary care cohorts and may perform differently in primary care. When we applied FIB-4 and NFS to our limited primary care NAFLD cohorts, the results revealed an abundance of high-risk scores, were often discrepant, and would have resulted in conflicting clinical decisions for 30% of the sample. Follow-up testing with liver stiffness measurement by vibration-controlled elastography can improve non-invasive test accuracy, but this technology is not currently available in primary care.29,30 In this proposal, the investigators seek to deploy a proactive diagnostic strategy to improve the primary care diagnosis of NAFLD (Aim 1) and evaluate EHR-based, patient-level clinical variables associated with a high-risk for advanced fibrosis identified by non-invasive risk scores and vibration-controlled elastography (Aim 2).

抽象的 改进原发性非酒精性脂肪肝的诊断和纤维化风险评估 护理肝脏化学异常的患者。 慢性肝病，包括非酒精性脂肪肝病（NAFLD）、酒精相关性肝病（ALD）、 和病毒性肝炎，往往在早期阶段未被发现，诊断延迟对患者直接有害。1,2 尽管慢性和终末期肝病患者人数不断增加，但普遍存在的诊断错误导致慢性和终末期肝病的死亡人数不断攀升。 治疗方案的可用性和疗效。3 肝脏化学物质升高可能预示着慢性肝病以及对这些异常的系统反应 可以更早地识别疾病并提供有效的治疗。4-11 目前，对异常的反应 初级保健中的肝脏检测缺乏一致性并导致诊断错误。11-17 我们的 K23 工作发现几乎 12%肝功能检查异常的患者缺乏重复评估，只有16%的患者连续接受肝功能检查 肝脏检查异常及时接受丙型肝炎病毒检测。14,16 这些有限且不一致的评估 挑战我们开发将患者水平变量与肝病诊断联系起来的模型的能力。 诊断 NAFLD 提出了独特的挑战，因为诊断需要阴性酒精暴露史、 全面排除其他肝脏疾病和/或腹部影像、无法接近或缺失的元素 11,18 尽管基于初级保健的风险因素包括肥胖、高血压和 糖尿病、NAFLD 在这种情况下仍然未被充分诊断。18-22 我们的 K23 工作强调了这一问题的严重性 诊断不足，因为只有 31% 的患者有肝脂肪变性的影像学证据，并且没有已知的（非 NAFLD) 慢性肝病 (n=767) 曾经收到过 NAFLD 的诊断代码。 除了诊断之外，初级保健中的 NAFLD 管理还需要进行纤维化风险评估，因为存在 晚期纤维化是这些患者肝脏相关死亡率、心血管死亡率和总体死亡率的最佳指标。23- 25 当前的纤维化风险评估从非侵入性风险评分开始，包括 Fibrosis-4 指数 (FIB-4) 和 NAFLD 纤维化评分 (NFS)，以确定最有可能从肝病转诊中受益的患者。6,18,26-28 FIB-4 和 NFS 是在专科和三级护理队列中开发和测试的，并且在以下方面可能表现不同 初级保健。当我们将 FIB-4 和 NFS 应用于有限的初级保健 NAFLD 队列时，结果显示 大量的高风险评分往往存在差异，并且会导致相互矛盾的临床决策 占样本的 30%。通过振动控制弹性成像进行肝脏硬度测量的后续测试 可以提高非侵入性测试的准确性，但这项技术目前在初级保健中尚不可用。29,30 在该提案中，研究人员寻求部署主动诊断策略以改善初级保健 诊断 NAFLD（目标 1）并评估与高风险相关的基于 EHR 的患者水平临床变量 用于通过非侵入性风险评分和振动控制弹性成像识别的晚期纤维化（目标 2）。