Detection of Undiagnosed Liver Cirrhosis via AI-Enabled Electrocardiogram: a Pragmatic, Cluster-Randomized Clinical Trial

Simonetto, D. A.

doi:10.1038/s41591-025-04058-y

Simonetto AI-ECG (cirrhosis)

Detection of Undiagnosed Liver Cirrhosis via AI-Enabled Electrocardiogram: a Pragmatic, Cluster-Randomized Clinical Trial

Patient / Population Intervention / Exposure Comparison Outcome

In 15,596 adults having a routine ECG in primary care, an AI-ECG alert for advanced chronic liver disease increased new diagnoses of chronic liver disease with advanced fibrosis within 180 days compared with usual care.

N

15,596patients

Design

Pragmatic cluster RCT (98 primary care teams)

Endpoint

New diagnosis of chronic liver disease with advanced fibrosis within 180 days of the ECG

Relevance

2Important — one of several pillars.

ResultAdvanced CLD diagnosed in 1.0% vs 0.5% (OR 2.09, 95% CI 1.22–3.55; P=0.007); among ECG-ML-positive patients 4.4% vs 1.1% (OR 4.37, 95% CI 1.94–9.88; P<0.001); any fibrosis (secondary) 1.7% vs 0.5% (OR 3.17, 95% CI 1.86–5.40; P<0.001).

Simonetto DA, et al. Nat Med. 2026;32(1):160-167. 10.1038/s41591-025-04058-y

Discussion & critique

Extends the EAGLE design beyond the heart: a routine ECG becomes a case-finding test for a non-cardiac disease, with targeted liver testing downstream. The diagnostic yield stayed well below epidemiological estimates of advanced CLD prevalence, which the authors attribute to variable clinician adherence to the AI recommendation — the same adoption bottleneck seen in EAGLE and Rushlow. Diagnosis, not liver outcomes, was the endpoint; open-label cluster design.