Identification of Candidates for MASLD Treatment With Indeterminate Vibration-Controlled Transient Elastography

David Marti-Aguado; José Miguel Carot-Sierra; Aida Villalba-Ortiz; Harris Siddiqi; Rose Marie Vallejo-Vigo; Carmen Lara-Romero; Marta Martín-Fernández; Matías Fernández-Patón; Clara Alfaro-Cervello; Ana Crespo; Elena Coello; Víctor Merino-Murgui; Egbert Madamba; Salvador Benlloch; Judith Pérez-Rojas; Víctor Puglia; Antonio Ferrández; Victoria Aguilera; Cristina Monton; Desamparados Escudero-García; Paloma Lluch; Rocío Aller; Rohit Loomba; Manuel Romero-Gomez; Luis Marti-Bonmati

doi:10.1016/j.cgh.2024.10.014

Identification of Candidates for MASLD Treatment With Indeterminate Vibration-Controlled Transient Elastography

Clin Gastroenterol Hepatol. 2024 Nov 16:S1542-3565(24)01037-1. doi: 10.1016/j.cgh.2024.10.014. Online ahead of print.

Authors

David Marti-Aguado¹, José Miguel Carot-Sierra², Aida Villalba-Ortiz², Harris Siddiqi³, Rose Marie Vallejo-Vigo⁴, Carmen Lara-Romero⁴, Marta Martín-Fernández⁵, Matías Fernández-Patón⁶, Clara Alfaro-Cervello⁷, Ana Crespo⁸, Elena Coello⁹, Víctor Merino-Murgui¹⁰, Egbert Madamba³, Salvador Benlloch¹¹, Judith Pérez-Rojas¹², Víctor Puglia¹³, Antonio Ferrández⁷, Victoria Aguilera¹⁴, Cristina Monton¹⁰, Desamparados Escudero-García¹⁵, Paloma Lluch¹⁵, Rocío Aller¹⁶, Rohit Loomba¹⁷, Manuel Romero-Gomez¹⁸, Luis Marti-Bonmati¹⁹

Affiliations

¹ Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain. Electronic address: [email protected].
² Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain.
³ MASLD Research Center, Division of Gastroenterology, University of California San Diego, La Jolla, California.
⁴ Digestive Diseases Department, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, Department of Medicine, University of Seville, Seville, Spain.
⁵ Department of Cell Biology, Genetics, Histology and Pharmacology, University of Valladolid, Valladolid, Spain; BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
⁶ Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain.
⁷ Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain.
⁸ Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain.
⁹ Digestive Disease Department, La Fe University and Polytechnic Hospital, Valencia, Spain.
¹⁰ Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain.
¹¹ Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.
¹² Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.
¹³ Pathology Department, Hospital Arnau de Vilanova, Valencia, Spain.
¹⁴ Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain.
¹⁵ Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain.
¹⁶ BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Department of Medicine, Dermatology and Toxicology, Universidad de Valladolid, Valladolid, Spain; Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
¹⁷ MASLD Research Center, Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California.
¹⁸ Digestive Diseases Department, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, Department of Medicine, University of Seville, Seville, Spain; University of Seville, Seville, Spain.
¹⁹ Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain; Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.

PMID: 39551253
DOI: 10.1016/j.cgh.2024.10.014

Abstract

Background and aims: A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.

Methods: This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization.

Results: From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients.

Conclusions: To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.

Keywords: Controlled Attenuation Parameter; Liver Stiffness Measurement; Metabolic Dysfunction–Associated Steatotic Liver Disease; Significant Fibrosis.