Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Statistical Analysis
3. Results
3.1. Demographic, Physical, and Lifestyle Characteristics
3.2. Disease History
3.3. Measured Parameters
3.4. Correlations Between UAP and LS and Other Characteristics
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Younossi, Z.M.; Golabi, P.; Paik, J.M.; Henry, A.; Van Dongen, C.; Henry, L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review. Hepatology 2023, 77, 1335–1347. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Younossi, Z.M.; Stepanova, M.; Al Shabeeb, R.; Eberly, K.E.; Shah, D.; Nguyen, V.; Ong, J.; Henry, L.; Alqahtani, S.A. The changing epidemiology of adult liver transplantation in the United States in 2013–2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Hepatol. Commun. 2023, 8, e0352. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol. 2024, 81, 492–542. [Google Scholar] [CrossRef] [PubMed]
- Berzigotti, A.; Tsochatzis, E.; Boursier, J.; Castera, L.; Cazzagon, N.; Friedrich-Rust, M.; Petta, S.; Thiele, M.; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis—2021 update. J. Hepatol. 2021, 75, 659–689. [Google Scholar] [CrossRef] [PubMed]
- Kariyama, K.; Nouso, K.; Toyoda, H.; Tada, T.; Hiraoka, A.; Tsuji, K.; Itobayashi, E.; Ishikawa, T.; Wakuta, A.; Oonishi, A.; et al. Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma. Cancers 2019, 11, 203. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Salomone, F.; Micek, A.; Godos, J. Simple Scores of Fibrosis and Mortality in Patients with NAFLD: A Systematic Review with Meta-Analysis. J. Clin. Med. 2018, 7, 219. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Newsome, P.N.; Ambery, P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J. Hepatol. 2023, 79, 1557–1565. [Google Scholar] [CrossRef] [PubMed]
- Loomba, R.; Hartman, M.L.; Lawitz, E.J.; Vuppalanchi, R.; Boursier, J.; Bugianesi, E.; Yoneda, M.; Behling, C.; Cummings, O.W.; Tang, Y.; et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N. Engl. J. Med. 2024, 391, 299–310. [Google Scholar] [CrossRef] [PubMed]
- Bandyopadhyay, S.; Das, S.; Samajdar, S.S.; Joshi, S.R. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Metab. Syndr. 2023, 17, 102849. [Google Scholar] [CrossRef] [PubMed]
- Wilding, J.P.H.; Batterham, R.L.; Calanna, S.; Davies, M.; Van Gaal, L.F.; Lingvay, I.; McGowan, B.M.; Rosenstock, J.; Tran, M.T.D.; Wadden, T.A.; et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N. Engl. J. Med. 2021, 384, 989–1002. [Google Scholar] [CrossRef] [PubMed]
- Newsome, P.N.; Buchholtz, K.; Cusi, K.; Linder, M.; Okanoue, T.; Ratziu, V.; Sanyal, A.J.; Sejling, A.S.; Harrison, S.A.; NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N. Engl. J. Med. 2021, 384, 1113–1124. [Google Scholar] [CrossRef] [PubMed]
- Harrison, S.A.; Taub, R.; Neff, G.W.; Lucas, K.J.; Labriola, D.; Moussa, S.E.; Alkhouri, N.; Bashir, M.R. Resmetirom for nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled phase 3 trial. Nat. Med. 2023, 29, 2919–2928. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Harrison, S.A.; Bedossa, P.; Guy, C.D.; Schattenberg, J.M.; Loomba, R.; Taub, R.; Labriola, D.; Moussa, S.E.; Neff, G.W.; Rinella, M.E.; et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N. Engl. J. Med. 2024, 390, 497–509. [Google Scholar] [CrossRef] [PubMed]
- The Lancet Gastroenterology Hepatology. Resmetirom for NASH: Balancing promise and prudence. Lancet Gastroenterol. Hepatol. 2024, 9, 273. [Google Scholar] [CrossRef] [PubMed]
- Petta, S.; Targher, G.; Romeo, S.; Pajvani, U.B.; Zheng, M.H.; Aghemo, A.; Valenti, L.V.C. The first MASH drug therapy on the horizon: Current perspectives of resmetirom. Liver Int. 2024, 44, 1526–1536. [Google Scholar] [CrossRef] [PubMed]
- Younossi, Z.M.; Stepanova, M.; Racila, A.; Henry, L.; Labriola, D.; Taub, R.; Nader, F. Health-related quality of life (HRQL) assessments in a 52-week, double-blind, randomized, placebo-controlled phase III study of resmetirom (MGL-3196) in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Hepatology 2024, 81, 1318–1327. [Google Scholar] [CrossRef] [PubMed]
- Loomba, R.; Sanyal, A.J.; Kowdley, K.V.; Bhatt, D.L.; Alkhouri, N.; Frias, J.P.; Bedossa, P.; Harrison, S.A.; Lazas, D.; Barish, R.; et al. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. N. Engl. J. Med. 2023, 389, 998–1008. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Harrison, S.A.; Frias, J.P.; Neff, G.; Abrams, G.A.; Lucas, K.J.; Sanchez, W.; Gogia, S.; Sheikh, M.Y.; Behling, C.; Bedossa, P.; et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): A multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol. Hepatol. 2023, 8, 1080–1093. [Google Scholar] [CrossRef] [PubMed]
- Gallego-Durán, R.; Ampuero, J.; Maya-Miles, D.; Pastor-Ramírez, H.; Montero-Vallejo, R.; Rivera-Esteban, J.; Álvarez-Amor, L.; Pareja, M.J.; Rico, M.C.; Millán, R.; et al. Fibroblast growth factor 21 is a hepatokine involved in MASLD progression. United Eur. Gastroenterol. J. 2024, 12, 1056–1068. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Cuschieri, S. The STROBE guidelines. Saudi J. Anaesth. 2019, 13 (Suppl. S1), S31–S34. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Dietrich, C.G.; Rau, M.; Geier, A. Screening for nonalcoholic fatty liver disease-when, who and how? World J. Gastroenterol. 2021, 27, 5803–5821. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Pandyarajan, V.; Gish, R.G.; Alkhouri, N.; Noureddin, M. Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic. Gastroenterol. Hepatol. 2019, 15, 357–365. [Google Scholar] [PubMed] [PubMed Central]
- Mohammadi, T.; Mohammadi, B. Screening the General Population for Non-Alcoholic Fatty Liver Disease: Model Development and Validation. Arch. Med. Res. 2024, 55, 102987. [Google Scholar] [CrossRef] [PubMed]
- Abeysekera, K.W.M.; Fernandes, G.S.; Hammerton, G.; Portal, A.J.; Gordon, F.H.; Heron, J.; Hickman, M. Prevalence of steatosis and fibrosis in young adults in the UK: A population-based study. Lancet Gastroenterol. Hepatol. 2020, 5, 295–305. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Zhang, S.; Mak, L.Y.; Yuen, M.F.; Seto, W.K. Screening strategy for non-alcoholic fatty liver disease. Clin. Mol. Hepatol. 2023, 29, S103–S122. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Chon, Y.E.; Jin, Y.J.; An, J.; Kim, H.Y.; Choi, M.; Jun, D.W.; Kim, M.N.; Han, J.W.; Lee, H.A.; Yu, J.H.; et al. Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Clin. Mol. Hepatol. 2024, 30, S117–S133. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Man, S.; Deng, Y.; Ma, Y.; Fu, J.; Bao, H.; Yu, C.; Lv, J.; Liu, H.; Wang, B.; Li, L. Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study with 5.7 Million Adults in China. Gastroenterology 2023, 165, 1025–1040. [Google Scholar] [CrossRef] [PubMed]
- Marchesini, G.; Bugianesi, E.; Burra, P.; Marra, F.; Miele, M.; Alisi, A.; Vajro, P.; Masarone, M.; Petta, S.; Persico, M.; et al. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO). Nutr. Metab. Cardiovasc. Dis. 2022, 32, 1–16. [Google Scholar] [CrossRef]
- Rebelos, E.; Iozzo, P.; Guzzardi, M.A.; Brunetto, M.R.; Bonino, F. Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease. World J. Gastroenterol. 2021, 27, 4999–5018. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
Variable | Overall N = 387 | Male N = 193 | Female N = 194 | p-Value |
---|---|---|---|---|
Age (years) | 63 ± 14 | 62 ± 15 | 63 ± 12 | n.s. |
BMI (kg/m2) | 26.2 ± 4.4 | 27.1 ± 4.3 | 25.4 ± 4.4 | <0.001 |
Waist circumference (cm) | 98 ± 15 | 103 ± 15 | 93 ± 15 | <0.001 |
HT (yes) | 128 (33%) | 56 | 72 | n.s. |
T2D (yes) | 18 (5%) | 8 | 10 | n.s. |
Alcohol consumption (yes:no) | 210:167 (54:43)% | 121:65 | 89:102 | <0.001 |
Smoker (yes:no:ex) | 45:273:63 (12:70:16)% | 22:127:39 | 23:146:24 | n.s. |
Sugary coffee (yes:no:ex) | 204:145:27 (53:37:7)% | 105:66:13 | 99:79:14 | n.s. |
Physical activity (Lacking:Moderate:Good) | 48:89:49 (12:23:13)% | 26:40:30 | 22:49:19 | n.s. |
UAP (dB/m) | 256 ± 44 | 264 ± 46 | 249 ± 42 | n.s. |
LS (kPa) | 7.5 ± 3.7 | 8.0 ± 4.3 | 138 ± 21 | n.s. |
Systolic pressure (mmHg) | 137 ± 18 | 135 ± 15 | 138 ± 21 | n.s. |
Diastolic pressure (mmHg) | 77 ± 10 | 77 ± 10 | 76 ± 11 | n.s. |
HR (bpm) | 75 ± 13 | 73 ± 13 | 77 ± 12 | n.s. |
Saturation (%) | 97 ± 2 | 97 ± 2 | 97 ± 2 | n.s. |
Univariate | Multivariate Model 1 1 | Multivariate Model 2 1 | ||||
---|---|---|---|---|---|---|
Variable | R | p | R | p | R | p |
Age | −0.102 | 0.534 | ||||
Sex | −15.004 | <0.001 | −9.571 | 0.061 | −9.633 | 0.069 |
BMI | 4.512 | <0.001 | 3.509 | <0.001 | 3.413 | <0.001 |
Waist circumference | 0.980 | <0.001 | 0.211 | 0.243 | 0.238 | 0.204 |
HT | 6.372 | 0.142 | ||||
T2D | 18.292 | 0.090 | 6.409 | 0.615 | ||
Non-smokers | −1.240 | 0.807 | ||||
Ex-smokers | −6.463 | 0.293 | ||||
Smokers | 10.982 | 0.120 | ||||
Alcohol | −7.031 | 0.129 | ||||
Sugary coffee | 0.389 | 0.933 | ||||
No sugary coffee | 3.924 | 0.409 | ||||
Ex-sugary coffee drinkers | −15.396 | 0.085 | −10.202 | 0.450 | ||
Physical activity: lacking | 13.476 | 0.035 | 8.440 | 0.137 | 7.669 | 0.192 |
Physical activity: moderate | −7.647 | 0.173 | ||||
Physical activity: good | −3.463 | 0.587 |
Univariate | Multivariate Model 1 1 | Multivariate Model 2 1 | ||||
---|---|---|---|---|---|---|
Variable | R | p | R | p | R | p |
Age | 0.022 | 0.100 | 0.027 | 0.057 | ||
Sex | −1.088 | 0.004 | −0.545 | 0.165 | −0.607 | 0.122 |
BMI | 0.246 | <0.001 | 0.160 | 0.006 | 0.182 | 0.002 |
Waist circumference | 0.068 | <0.001 | 0.031 | 0.074 | 0.024 | 0.171 |
HT | 0.329 | 0.362 | ||||
T2D | 0.764 | 0.39 | ||||
Non-smokers | 0.087 | 0.836 | ||||
Ex-smokers | 0.030 | 0.954 | ||||
Smokers | −0.209 | 0.722 | ||||
Alcohol | 0.253 | 0.510 | ||||
Sugary coffee | 0.234 | 0.526 | ||||
No sugary coffee | −0.397 | 0.293 | ||||
Ex-sugary coffee drinkers | 0.540 | 0.449 | ||||
Physical activity: lacking | 0.814 | 0.200 | ||||
Physical activity: moderate | −0.588 | 0.290 | ||||
Physical activity: good | −0.047 | 0.941 |
Variable | LS | UAP | |||
---|---|---|---|---|---|
R | p | R | p | ||
BMI (kg/m2) | No T2D | 0.334 | <0.001 | 0.441 | <0.001 |
T2D | 0.090 | n.s. | 0.553 | <0.05 | |
Waist circumference (cm) | No T2D | 0.307 | <0.001 | 0.324 | <0.001 |
T2D | −0.042 | n.s. | 0.468 | <0.05 |
LS </≥ 7 kPa N = 232/155 | UAP </≥ 230 dB/m N = 108/279 | |
---|---|---|
T2D | - | - |
HT | <0.05 | - |
Sex | <0.05 | <0.05 |
Alcohol | - | <0.001 |
Smokers | - | - |
Sugary coffee | - | <0.05 |
Physical activity | <0.05 | - |
Age | <0.05 | - |
BMI | <0.001 | <0.001 |
Waist circumference | <0.001 | <0.01 |
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De Rosa, L.; Ricco, G.; Brunetto, M.R.; Bonino, F.; Faita, F. Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study. Healthcare 2025, 13, 759. https://doi.org/10.3390/healthcare13070759
De Rosa L, Ricco G, Brunetto MR, Bonino F, Faita F. Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study. Healthcare. 2025; 13(7):759. https://doi.org/10.3390/healthcare13070759
Chicago/Turabian StyleDe Rosa, Laura, Gabriele Ricco, Maurizia Rossana Brunetto, Ferruccio Bonino, and Francesco Faita. 2025. "Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study" Healthcare 13, no. 7: 759. https://doi.org/10.3390/healthcare13070759
APA StyleDe Rosa, L., Ricco, G., Brunetto, M. R., Bonino, F., & Faita, F. (2025). Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study. Healthcare, 13(7), 759. https://doi.org/10.3390/healthcare13070759