Introduction

The availability of new drugs for the treatment of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) underlines the need of early predictors of response to such therapies. This study evaluated the impact of 1-year changes in liver stiffness measurement by Vibration-Controlled Transient Elastography (LSM by VCTE), controlled attenuation parameters (CAP), and serum alanine aminotransferase (ALT) on liver outcomes in patients with MASLD.

Aims & Methods

A large multicenter cohort of MASLD patients with LSM≥8kPa and prospective follow-up was enrolled. Liver-related events (LRE), including hepatocellular carcinoma (HCC) and liver decompensation (LD), were evaluated during follow-up. LSM, CAP, and ALT were assessed at baseline and at 1-year follow-up. Cumulative incidence functions and cause-specific Cox regression analyses were performed to correlate 1-year reduction in LSM, CAP, and ALT with the risk of developing LRE, LD and HCC.

Results

In 2443 patients with MASLD and LSM≥8kPa, a 1-year reduction in ALT of 17 IU/L (HR 0.62; 95% CI 0.41-0.95; p=0.02) and a 20% reduction in LSM (HR 0.44; 95% CI 0.29-0.67; p<0.001) were both independently associated with a lower risk of LRE. Similarly, in 1412 patients with MASLD and LSM≥10kPa, a 1-year reduction in ALT of at least 17 IU/L (HR 0.62; 95% CI 0.39-0.98; p=0.04) and a 20% reduction in LSM (HR 0.42; 95% CI 0.27-0.66; p<0.001) were independently associated with a decreased risk of LRE. Comparable results were observed when considering LD separately, but not for HCC. One-year changes in CAP did not predict liver outcomes. When combining 1-year reduction in ALT of 17 IU/L and a 1-year 20% reduction in LSM, the 5-year probabilities of LRE ranged from 2.1% in the best profile to 5% in the worst profile in patients with LSM≥8kPa, and from 3.3% to 8.1% in those with LSM≥10kPa.

Conclusion

One-year reductions in ALT of 17 IU/L and in LSM by 20%, but not changes in CAP, reduce long-term liver outcomes in patients with MASLD, providing suggestion on monitoring therapy effectiveness.

Introduction

Eosinophilic esophagitis (EoE) is type-2 chronic inflammatory disorder usually accompanied by other atopic conditions including rhinitis, conjunctivitis, bronchial asthma, dermatitis, hives or chronic rhinosinusitis with nasal polyps. The influence of these atopies in the response to the EoE therapy has been barely investigated, with opposite results in small cohorts (1,2).

Aims & Methods

We aim to describe atopic concomitances in European EoE patients and to evaluate its influence on effectiveness of first-line therapy, consisting in proton-pump inhibitors (PPIs), swallowed topical corticosteroids (STCs) and food-elimination diets (FEDs).
A cross-sectional analysis of the multicenter EoE CONNECT registry (3) was performed. Demographic and clinical data from patients recruited at 42 hospitals in 4 European countries were extracted on March 25^th, 2025. Concomitant atopies were classified as seasonal or persistent. Clinico-histological response (CHR) was defined as the simultaneous presence of symptomatic remission and a peak eosinophil count <15 eosinophils per high power field after therapy.

Results

Overall, 3,900 patients (75.6% males, mean age 33.3 ±15.1 years) were analyzed (Table). CHR rate after first-line monotherapy with PPIs, STCs or FEDs was 50.4% (n=2,685). PPIs was the only treatment affected by concomitant atopy: presence of asthma and hives significantly reduced CHR rates to PPIs (42.7% vs 49.7%, p=0.005, and 39.3% vs 48%, p=0.044, respectively), and CHR also tended to be lower in presence of conjunctivitis (43.6% vs 48.4, p=0.067) and dermatitis (43.2% vs 48.3%, p=0.081). Seasonal or persistent presentation of atopy did not influence response to treatment. Taking into account age at diagnosis, the effect of concomitant atopy in reducing CHR to PPIs was exclusively observed in adults (≥18 years old) for asthma (43.8% vs 51.3%, p=0.007) and dermatitis (42.6% vs 50.3%, p=0.026), and in children (<18 years old) for hives (17.4% vs 39.9%, p=0.032).
We next analyzed whether the number of concomitant atopies influenced CHR to first-line therapy. While no differences were found among patients who presented only one atopic condition, the presence of 2 or more atopies reduced PPI effectiveness in adults (45.0% vs 50.7%, p=0.032) and to FEDs in children (23.5% vs 59.3%, p=0.020). A reduction in CHR rate after PPI therapy was even greater in adults with 3 or more atopies concomitant to EoE (39.0% vs 50.4%, p=0.001). Effectiveness of first-line STCs were not affected in any of these comparisons.

Conclusion

The coexistence of asthma, dermatitis and hives determined lower response to PPI therapy for EoE. Association of 2 or more atopic condition further decreased effectiveness of PPIs in adults and of FEDs in children.

References

1. Ancellin M, Ricolfi-Waligova L, Clerc-Urmès I, et al. Management of eosinophilic esophagitis in children according to atopic status: a retrospective cohort in northeast of France. Arch Pediatr. 2020;27(3):122-127.
2. Reed WD, Ocampo AA, Xue Z, et al. Eosinophilic esophagitis patients with multiple atopic conditions: clinical characteristics and treatment response to topical steroids. Ann Allergy Asthma Immunol. 2023;131(1): 109-115.e2.
3. Lucendo AJ, Santander C, Savarino E, et al. EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe. Therap Adv Gastroenterol. 2022;15:17562848221074204.