Contrast-enhanced Ultrasound and the Lerner Histopathological Grade in Gastrointestinal Graft-versus-host Disease: A...

Gastrointestinal graft-versus-host disease (GI GVHD) is a major complication of allogeneic haematopoietic stem-cell transplantation (allo-HSCT). Endoscopic biopsy with histopathological grading according to the Lerner system remains the diagnostic standard, although invasive sampling is frequently constrained in this fragile population. We assessed the relationship between a four-parameter contrast-enhanced ultrasound (CEUS) score and the Lerner histopathological grade.

Prospective, single-centre study (October 2018 - December 2025). Adult allo-HSCT recipients with new-onset gastrointestinal symptoms underwent multimodal abdominal ultrasound, including CEUS with sulphur hexafluoride microbubbles, followed by endoscopic biopsy. A composite CEUS-GVHD score (range 0-12) integrated bowel-wall thickness, bowel-loop dilatation, contrast wash-out, and transmural microbubble migration. The cohort comprised 51 episodes (in 41 unique patients) with histopathologically confirmed GI GVHD and Lerner grade I-IV. A within-patient sensitivity analysis was performed on the first chronologically documented episode per patient (n=41), and additional sensitivity analyses were performed by stratification according to concurrent gastrointestinal infection and according to GVHD form (acute vs chronic).

The total CEUS-GVHD score showed a positive correlation with the Lerner grade (p < 0.001). Median CEUS scores across grades were 5.5 (Lerner I), 7 (II), 8.5 (III), and 10 (IV) (p < 0.001). Among individual parameters, transmural microbubble migration showed the highest correlation, followed by bowel-wall thickness and contrast wash-out; these three correlations remained significant after Bonferroni correction. The bowel-loop dilatation correlation did not retain significance after correction. In an exploratory analysis, the area under the ROC curve of the total CEUS-GVHD score for discriminating severe (Lerner III-IV) from mild (Lerner I-II) histopathological GI GVHD was 0.853, with the same point estimate retained in the within-patient sensitivity analysis (AUC 0.853).

In this single-centre cohort of biopsy-confirmed GI GVHD, the CEUS-GVHD score showed a moderate-to-strong association with Lerner histopathological grade. Because the study included only confirmed GI GVHD episodes, these findings support CEUS as a potential adjunct for severity assessment, not as a replacement for diagnostic biopsy. External multicentre validation with multiple operators is required.