AI-assisted, single-fiber digital pathology quantification of changes in liver fibrosis after bariatric surgery

Background: In steatohepatitis trials, antifibrotic effects are measured by conventional histology, albeit with significant limitations. We assessed how artificial intelligence–assisted, single-fiber quantitative image analysis of hepatic fibrosis matrix measures fibrosis reversal following an intervention that results in major histological improvement. Methods: Fifty-eight patients underwent bariatric surgery with preoperative and follow-up (>1 y) liver biopsies. High-resolution, single-fiber quantitative image analysis extracted quantitative traits of fibrosis, which were combined in a continuous phenotypic fibrosis composite score (Ph-FCS) of fibrosis severity. Changes in Ph-FCS were compared between patients with increasing, decreasing, or stable histological fibrosis stage. Results: The mean follow-up between biopsies was 5.84 years (SD 2.59). Forty patients improved in histological fibrosis stage, 12 were unchanged, and 6 progressed. Median Ph-FCS was reduced from 5.25 at baseline to 3.75 at follow-up ( p <0.001). Baseline Ph-FCS was correlated with Ph-FCS reduction after surgery ( r =0.72, p <0.001). Ph-FCS reduction was higher in patients with a histological ≥1-stage reduction (−1.78, 95% CI: −2.15 to −1.04) than in those unchanged (−1.08, 95% CI: −1.93 to 0.01) or with progression (−0.28, 95% CI: −1.26 to 0.71) ( p <0.02 for differences between groups). The Ph-FCS identified intrastage fibrosis reduction in 9 patients labeled unchanged by conventional histology. Of 34 patients with advanced fibrosis at baseline, 15 still had advanced fibrosis according to histological staging. Despite similar histological staging, their follow-up Ph-FCS was reduced from baseline, although it remained higher than that of the 19 who regressed. Conclusions: Artificial intelligence–assisted, single-fiber image analysis provides an automated measurement of fibrosis changes, which is quantitative and more sensitive to change than conventional pathology and thus can improve the feasibility of antifibrotic trials.