Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

Miguel Sogbe; Breianna Hummer; Jonathan G. Stine; Blanca Lizaola-Mayo; Daniel E. Forman; Hugo E. Vargas; Andres Duarte-Rojo

doi:10.1007/s10620-025-08893-4

Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

Miguel Sogbe, Breianna Hummer, Jonathan G. Stine, Blanca Lizaola-Mayo, Daniel E. Forman, Hugo E. Vargas, Andres Duarte-Rojo^*

^*Corresponding author for this work

Medicine, Hepatology Division

Research output: Contribution to journal › Article › peer-review

Abstract

Background: MASLD is a leading reason for liver transplant waitlisting. The relationship between cardiorespiratory fitness (CRF) and liver fibrosis in patients with MASLD remains unclear. This study aims to provide further evidence supporting the relationship between liver fibrosis and CRF. Methods: Participants with MASLD across various fibrosis stages, including those with cirrhosis awaiting liver transplantation from three U.S. transplant centers, underwent cardiopulmonary exercise testing (CPX). We compared participants based on fibrosis stage (F0-F1, F2-F3, and F4) and CPX parameters such as VO_2peak, respiratory exchange ratio (RER), ventilatory efficiency (VE/VCO₂), double product (DP) and chronotropic incompetence (CI). Multivariable models were then built to evaluate factors associated with these parameters. Results: Sixty-one participants underwent CPX testing across three centers. Participants with F4 had lower VO_2peak (11.8 mL/kg/min) compared to F0-F1 (22.2 mL/kg/min) and F2-F3 (22.9 mL/kg/min), p < 0.001. Participants with F4 had higher RER (median 1.25) compared to F0-F1 (1.08) and F2-F3 (1.05), p = 0.001. Similarly, F4 participants exhibited higher VE/VCO₂ (median 36.5) compared to F0-F1 (31) and F2-F3 (30), p < 0.001. Additionally, F4 participants had lower DP values (median 17,696) compared to F0-F1 (25,460) and F2-F3 (25,372), and higher prevalence of CI (90%) compared to F0-F1 (39%) and F2-F3 (25%), both p = < 0.001. Multivariable modeling confirmed advanced fibrosis (F > 3) as an independent predictor of low CRF. Conclusions: In MASLD patients, advanced liver fibrosis, particularly cirrhosis, is associated with reduced CRF and poorer hemodynamic performance during CPX. Prioritizing exercise training for those in earlier stages (F3) may prevent fitness decline, which could hinder physical training and liver transplantation candidacy.

Original language	English (US)
Journal	Digestive diseases and sciences
DOIs	https://doi.org/10.1007/s10620-025-08893-4
State	Accepted/In press - 2025

Funding

Research reported in this publication was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award numbers K23DK131290 (JS) and L30DK118601 (JS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Study was also funded by the NIDDK award P30DK120531 (ADR) Pilot and Feasibility Program, Cycle 2020, and by NIH/NCATS Grant UL1TR000127 and UL1TR002014. This project was also funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds (JS). The Department specifically disclaims responsibility for any analyses, interpretations, or conclusion.

Keywords

Cardiopulmonary exercise testing
Cirrhosis
Liver transplant
Metabolic dysfunction-associated steatotic liver disease

ASJC Scopus subject areas

Physiology
Gastroenterology

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10.1007/s10620-025-08893-4

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@article{f93477cdd6084cabb730b1b79e1599cb,

title = "Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease",

abstract = "Background: MASLD is a leading reason for liver transplant waitlisting. The relationship between cardiorespiratory fitness (CRF) and liver fibrosis in patients with MASLD remains unclear. This study aims to provide further evidence supporting the relationship between liver fibrosis and CRF. Methods: Participants with MASLD across various fibrosis stages, including those with cirrhosis awaiting liver transplantation from three U.S. transplant centers, underwent cardiopulmonary exercise testing (CPX). We compared participants based on fibrosis stage (F0-F1, F2-F3, and F4) and CPX parameters such as VO2peak, respiratory exchange ratio (RER), ventilatory efficiency (VE/VCO2), double product (DP) and chronotropic incompetence (CI). Multivariable models were then built to evaluate factors associated with these parameters. Results: Sixty-one participants underwent CPX testing across three centers. Participants with F4 had lower VO2peak (11.8 mL/kg/min) compared to F0-F1 (22.2 mL/kg/min) and F2-F3 (22.9 mL/kg/min), p < 0.001. Participants with F4 had higher RER (median 1.25) compared to F0-F1 (1.08) and F2-F3 (1.05), p = 0.001. Similarly, F4 participants exhibited higher VE/VCO2 (median 36.5) compared to F0-F1 (31) and F2-F3 (30), p < 0.001. Additionally, F4 participants had lower DP values (median 17,696) compared to F0-F1 (25,460) and F2-F3 (25,372), and higher prevalence of CI (90%) compared to F0-F1 (39%) and F2-F3 (25%), both p = < 0.001. Multivariable modeling confirmed advanced fibrosis (F > 3) as an independent predictor of low CRF. Conclusions: In MASLD patients, advanced liver fibrosis, particularly cirrhosis, is associated with reduced CRF and poorer hemodynamic performance during CPX. Prioritizing exercise training for those in earlier stages (F3) may prevent fitness decline, which could hinder physical training and liver transplantation candidacy.",

keywords = "Cardiopulmonary exercise testing, Cirrhosis, Liver transplant, Metabolic dysfunction-associated steatotic liver disease",

author = "Miguel Sogbe and Breianna Hummer and Stine, {Jonathan G.} and Blanca Lizaola-Mayo and Forman, {Daniel E.} and Vargas, {Hugo E.} and Andres Duarte-Rojo",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.",

year = "2025",

doi = "10.1007/s10620-025-08893-4",

language = "English (US)",

journal = "Digestive diseases and sciences",

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T1 - Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

AU - Sogbe, Miguel

AU - Hummer, Breianna

AU - Stine, Jonathan G.

AU - Lizaola-Mayo, Blanca

AU - Forman, Daniel E.

AU - Vargas, Hugo E.

AU - Duarte-Rojo, Andres

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

PY - 2025

Y1 - 2025

N2 - Background: MASLD is a leading reason for liver transplant waitlisting. The relationship between cardiorespiratory fitness (CRF) and liver fibrosis in patients with MASLD remains unclear. This study aims to provide further evidence supporting the relationship between liver fibrosis and CRF. Methods: Participants with MASLD across various fibrosis stages, including those with cirrhosis awaiting liver transplantation from three U.S. transplant centers, underwent cardiopulmonary exercise testing (CPX). We compared participants based on fibrosis stage (F0-F1, F2-F3, and F4) and CPX parameters such as VO2peak, respiratory exchange ratio (RER), ventilatory efficiency (VE/VCO2), double product (DP) and chronotropic incompetence (CI). Multivariable models were then built to evaluate factors associated with these parameters. Results: Sixty-one participants underwent CPX testing across three centers. Participants with F4 had lower VO2peak (11.8 mL/kg/min) compared to F0-F1 (22.2 mL/kg/min) and F2-F3 (22.9 mL/kg/min), p < 0.001. Participants with F4 had higher RER (median 1.25) compared to F0-F1 (1.08) and F2-F3 (1.05), p = 0.001. Similarly, F4 participants exhibited higher VE/VCO2 (median 36.5) compared to F0-F1 (31) and F2-F3 (30), p < 0.001. Additionally, F4 participants had lower DP values (median 17,696) compared to F0-F1 (25,460) and F2-F3 (25,372), and higher prevalence of CI (90%) compared to F0-F1 (39%) and F2-F3 (25%), both p = < 0.001. Multivariable modeling confirmed advanced fibrosis (F > 3) as an independent predictor of low CRF. Conclusions: In MASLD patients, advanced liver fibrosis, particularly cirrhosis, is associated with reduced CRF and poorer hemodynamic performance during CPX. Prioritizing exercise training for those in earlier stages (F3) may prevent fitness decline, which could hinder physical training and liver transplantation candidacy.

AB - Background: MASLD is a leading reason for liver transplant waitlisting. The relationship between cardiorespiratory fitness (CRF) and liver fibrosis in patients with MASLD remains unclear. This study aims to provide further evidence supporting the relationship between liver fibrosis and CRF. Methods: Participants with MASLD across various fibrosis stages, including those with cirrhosis awaiting liver transplantation from three U.S. transplant centers, underwent cardiopulmonary exercise testing (CPX). We compared participants based on fibrosis stage (F0-F1, F2-F3, and F4) and CPX parameters such as VO2peak, respiratory exchange ratio (RER), ventilatory efficiency (VE/VCO2), double product (DP) and chronotropic incompetence (CI). Multivariable models were then built to evaluate factors associated with these parameters. Results: Sixty-one participants underwent CPX testing across three centers. Participants with F4 had lower VO2peak (11.8 mL/kg/min) compared to F0-F1 (22.2 mL/kg/min) and F2-F3 (22.9 mL/kg/min), p < 0.001. Participants with F4 had higher RER (median 1.25) compared to F0-F1 (1.08) and F2-F3 (1.05), p = 0.001. Similarly, F4 participants exhibited higher VE/VCO2 (median 36.5) compared to F0-F1 (31) and F2-F3 (30), p < 0.001. Additionally, F4 participants had lower DP values (median 17,696) compared to F0-F1 (25,460) and F2-F3 (25,372), and higher prevalence of CI (90%) compared to F0-F1 (39%) and F2-F3 (25%), both p = < 0.001. Multivariable modeling confirmed advanced fibrosis (F > 3) as an independent predictor of low CRF. Conclusions: In MASLD patients, advanced liver fibrosis, particularly cirrhosis, is associated with reduced CRF and poorer hemodynamic performance during CPX. Prioritizing exercise training for those in earlier stages (F3) may prevent fitness decline, which could hinder physical training and liver transplantation candidacy.

KW - Cardiopulmonary exercise testing

KW - Cirrhosis

KW - Liver transplant

KW - Metabolic dysfunction-associated steatotic liver disease

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Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

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