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-base...