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

摘要 提高非酒精性脂肪性肝病的诊断和纤维化风险评估水平 护理肝脏化学异常的患者。 慢性肝病，包括非酒精性脂肪性肝病(NAFLD)、酒精相关性肝病(ALD)、 和病毒性肝炎，通常在早期阶段没有被发现，这是对患者直接有害的诊断延误。 普遍的诊断错误加剧了慢性和终末期肝病的死亡人数不断攀升，尽管 治疗选择的可用性和有效性。3 肝脏化学升高可能是慢性肝病的信号，以及对这些异常的系统反应 可以导致疾病更早的认识和有效的治疗。4-11目前，反应异常 初级保健中的肝脏测试缺乏一致性，并导致诊断错误。11-17我们的K23工作发现 12%的肝功能异常患者缺乏重复评估，只有16%的患者连续 肝脏检测异常得到及时的丙型肝炎病毒检测。14、16这些有限和不一致的评估 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具有独特的挑战，因为诊断需要阴性的酒精暴露史， 全面排除其他肝脏疾病和/或腹部成像，无法接触到或不存在的因素 在电子健康记录中。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在这种情况下仍然被低估。18-22我们的K23工作突出了这一问题的严重性 诊断不足，因为只有31%的患者有肝脏脂肪变性的放射学证据，并且没有已知的(非 NAFLD)慢性肝病(n=767)曾经接受过NAFLD的诊断代码。 除了诊断之外，初级保健中的NAFLD管理需要进行纤维化风险评估，因为 晚期纤维化是这些患者肝脏相关、心血管疾病和总体死亡率的最佳指标。 目前的25项纤维化风险评估始于无创风险评分，包括纤维化-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，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，往往是不一致的，可能会导致相互矛盾的临床决定 30%的样品。振动控制弹性成像测量肝脏硬度的随诊试验 可以提高非侵入性检测的准确性，但这项技术目前还不适用于初级保健。 在这项提案中，研究人员试图部署一种积极主动的诊断策略来改善初级保健 NAFLD的诊断(AIM 1)和评估基于EHR的、与高危相关的患者水平的临床变量 对于通过非侵入性风险评分和振动控制弹性成像确定的晚期纤维化(目标2)。

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).