Diagnosis of NAFLD with and without fibrosis using a lower ALT reference range in the iLFT system

Background and aims: Up to 30% of people with non-alcoholic fatty liver disease (NAFLD) are at risk of cirrhosis and subsequent decompensation, making it crucial to identify them early. Using the conventional normal ALT range (≥55 U/L), rather than the true healthy normal range (≥30 U/L), risks missing many potential NAFLD cases. Intelligent liver function testing (iLFT) uses minimal diagnostic criteria and non-invasive fibrosis scores to automatically investigate abnormal LFTs, generating diagnoses and management plans in primary care. This saved costs and increased liver disease diagnoses by 44% using the conventional ALT range. As part of a secondary project, iLFT also triggered cascades for patients with ALT ≥30 U/L. This study investigates the impact of this on NAFLD diagnosis.

Method: A retrospective analysis was performed to identify all NAFLD diagnoses with and without abnormal NAFLD Fibrosis Score or Fib-4 score detected by iLFT between 2016-22. Patients were stratified into three groups: ALT 30-41 U/L, ALT 42-54 U/L and ALT ≥55 U/L. Clinical records were reviewed to determine if patients were referred to liver clinics, if Enhanced Liver Fibrosis (ELF) score or transient elastography (TE) was performed, and the final diagnosis.

Results: 16, 373 cases were identified in total. iLFT detected 986 NAFLD cases with normal fibrosis scores. 211 (21%) had ALT 30-41 U/L, 196 (20%) had ALT 42-54 U/L, and 509 (52%) had ALT ≥55 U/L. These patients were managed in primary care. iLFT detected 871 NAFLD cases with indeterminate or high risk for advanced fibrosis scores: 139 (16%) had ALT 30-41 U/L; 137 (16%) had ALT 42-54 U/L; and 493 (57%) had ALT ≥55 U/L. 576 (66%) were referred to liver clinics. Of those, 111 (19%) patients had ELF scores suggesting low risk of advanced fibrosis (<9.8) and were not seen. 173 (30%) patients had a final diagnosis of NAFLD with evidence of fibrosis; 25 (15%) had ALT 30-41 U/L; 32 (19%) had ALT 42-54 U/L; and 116 (67%) had ALT ≥55 U/L. Of those, 123 (71%) had moderate-severe fibrosis on TE or clinical decompensation. 17 (14%) had ALT 30-41 U/L; 23 (19%) had ALT 42-54 U/L; and 74 (60%) had ALT ≥50 U/L. 171 (37%) patients had a diagnosis of NAFLD without fibrosis, and 76 (16%) patients had a non-NAFLD diagnosis.

Conclusion: A substantial proportion (33%) of NAFLD patients with fibrosis had ALT between 30-54 U/L. This meant that iLFT referred 57 patients for further assessment who would otherwise have been missed using the conventional ALT range. This suggests we should consider lowering the reference range for ALT to improve the diagnosis of NAFLD in primary care.