Liver Fibrosis and IRS1 rs2972146 Are Associated With Weight Loss Response After Metabolic Bariatric Surgery
- 1SC Medicina ad Indirizzo Metabolico Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milan Italy
- 2Department of Pathophysiology and Transplantation University of Milan Milan Italy
- 3Department of General and Minimally‐Invasive Surgery Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy
Abstract
Background and Aims: Weight loss after metabolic bariatric surgery (MBS) is heterogeneous, and the contribution of liver histology and genetic susceptibility to insufficient weight loss (IWL) or weight regain (WR) remains unclear. We assessed the prevalence of IWL and WR after MBS and their association with liver histology and metabolic dysfunction‐associated steatotic liver disease (MASLD)‐related genetic variants.
Methods: We retrospectively included 351 adults undergoing MBS at Policlinico Hospital in Milan, between 2008 and 2023, with intraoperative liver biopsy. IWL was defined at 18 months as < 50% excess weight loss and/or BMI ≥ 35 kg/m2, WR as ≥ 10% increase from postoperative weight nadir. PNPLA3, TM6SF2, GCKR, HSD17B13, and IRS1 variants were genotyped.
Results: Out of 351 patients, 109 (31.1%) had IWL and out of 280 patients with available data, 91 (32.5%) developed WR. Hypertension (OR 1.97, 95% CI: 1.06–3.63) and significant liver fibrosis (OR 2.93, 95% CI: 1.07–8.01) were positively independently associated with IWL, whereas the IRS1 rs2972146 variant (OR 0.30, 95% CI: 0.14–0.62), sleeve gastrectomy or gastric bypass (OR 0.20, 95% CI: 0.10–0.39), dietary (OR 0.32, 95% CI: 0.16–0.63) and physical activity adherence (OR 0.38, 95% CI: 0.16–0.89) were inversely associated with IWL. WR was associated with psychiatric comorbidity and inversely associated with preoperative BMI, sleeve gastrectomy/gastric bypass, and dietary adherence.
Conclusions: Weight loss failure affected nearly one third of patients after MBS. Significant liver fibrosis and IRS1 rs2972146 variant may help identify patients at risk of suboptimal postoperative weight loss outcomes.
Related
- Adipose Tissue Pericellular Fibrosis, Weight Loss and Features of Metabolic Dysfunction-Associated Steatotic Liver Disease after Bariatric Surgery
- Factors Associated with Postoperative Hemorrhage in Primary Metabolic Bariatric Surgery: Nationwide Analysis of Patient Characteristics, Surgical and Stapling Techniques
- Greater early weight loss after metabolic/bariatric surgery predicts greater loss up to 2 years but is also associated with weight regain in the longer term.
- Prediction Models Versus Fibrosis-4 Index (FIB-4) for Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Verification-Audited Systematic Review and Meta-Analysis
- Comparison of Metabolic Dysfunction‐Associated Steatotic Liver Disease Between Individuals With Werner Syndrome and Those With Insulin‐Resistant Type 2 Diabetes: Hepatic Steatosis and Fibrosis Indices
BibTeX
@article{cinque2026liver,
title = {{Liver Fibrosis and IRS1 rs2972146 Are Associated With Weight Loss Response After Metabolic Bariatric Surgery}},
author = {Felice Cinque and Marica Meroni and Sara Badiali and Miriam Longo and Erika Paolini and Elisa Galfrascoli and Giovanna Oberti and Giuseppina Pisano and Gabriele Maffi and Matteo Mureddu and Elena Corbetta and Valentina Scimè and Emma Calzavara and Francesca Alletto and Annalisa Cespiati and Luigi Boni and Anna Ludovica Fracanzani and Paola Dongiovanni and Rosa Lombardi},
journal = {Diabetes, Obesity \& Metabolism},
year = {2026},
month = sep,
doi = {10.1111/dom.71345},
url = {https://doi.org/10.1111/dom.71345},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Liver Fibrosis and IRS1 rs2972146 Are Associated With Weight Loss Response After Metabolic Bariatric Surgery
AU - Felice Cinque
AU - Marica Meroni
AU - Sara Badiali
AU - Miriam Longo
AU - Erika Paolini
AU - Elisa Galfrascoli
AU - Giovanna Oberti
AU - Giuseppina Pisano
AU - Gabriele Maffi
AU - Matteo Mureddu
AU - Elena Corbetta
AU - Valentina Scimè
AU - Emma Calzavara
AU - Francesca Alletto
AU - Annalisa Cespiati
AU - Luigi Boni
AU - Anna Ludovica Fracanzani
AU - Paola Dongiovanni
AU - Rosa Lombardi
PY - 2026
DA - 2026/09/17
JO - Diabetes, Obesity & Metabolism
DO - 10.1111/dom.71345
UR - https://doi.org/10.1111/dom.71345
AB - Background and Aims: Weight loss after metabolic bariatric surgery (MBS) is heterogeneous, and the contribution of liver histology and genetic susceptibility to insufficient weight loss (IWL) or weight regain (WR) remains unclear. We assessed the prevalence of IWL and WR after MBS and their association with liver histology and metabolic dysfunction‐associated steatotic liver disease (MASLD)‐related genetic variants. Methods: We retrospectively included 351 adults undergoing MBS at Policlinico Hospital in Milan, between 2008 and 2023, with intraoperative liver biopsy. IWL was defined at 18 months as < 50% excess weight loss and/or BMI ≥ 35 kg/m2, WR as ≥ 10% increase from postoperative weight nadir. PNPLA3, TM6SF2, GCKR, HSD17B13, and IRS1 variants were genotyped. Results: Out of 351 patients, 109 (31.1%) had IWL and out of 280 patients with available data, 91 (32.5%) developed WR. Hypertension (OR 1.97, 95% CI: 1.06–3.63) and significant liver fibrosis (OR 2.93, 95% CI: 1.07–8.01) were positively independently associated with IWL, whereas the IRS1 rs2972146 variant (OR 0.30, 95% CI: 0.14–0.62), sleeve gastrectomy or gastric bypass (OR 0.20, 95% CI: 0.10–0.39), dietary (OR 0.32, 95% CI: 0.16–0.63) and physical activity adherence (OR 0.38, 95% CI: 0.16–0.89) were inversely associated with IWL. WR was associated with psychiatric comorbidity and inversely associated with preoperative BMI, sleeve gastrectomy/gastric bypass, and dietary adherence. Conclusions: Weight loss failure affected nearly one third of patients after MBS. Significant liver fibrosis and IRS1 rs2972146 variant may help identify patients at risk of suboptimal postoperative weight loss outcomes.
SN - 1462-8902
SN - 1463-1326
ER -