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Low skeletal muscle mass is associated with more severe histological features of non-alcoholic fatty liver disease in male

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Abstract

Background/purpose of the study

Although low skeletal muscle mass is associated with non-alcoholic fatty liver disease (NAFLD), it is currently uncertain whether there are associations between weight-adjusted appendicular skeletal muscle (ASM%), severity of histological features of NAFLD, and the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. Our aim was to test for a possible influence of the PNPLA3 rs738409 variant on the association between ASM% and severity of NAFLD histological features.

Methods

We enrolled 401 Chinese male with biopsy-proven NAFLD. Using a bioelectrical-impedance body composition analyzer (BIA, Inbody 720, Japan Inc., Tokyo), we calculated the ASM% as the percentage of total appendicular skeletal muscle mass (ASM, kg)/total body mass (kg) × 100.

Results

Compared to those with high ASM%, patients with low ASM% (≤ 30.6, i.e., the median value of distribution of the whole sample) had a greater severity of individual histological features of NAFLD. These patients also had a higher risk of severe steatosis and non-alcoholic steatohepatitis (NASH) (adjusted-odds ratio [OR] 2.34, 95% CI 1.39–3.93, and adjusted-OR 2.22, 95% CI 1.30–3.77) even after adjusting for age, body mass index, diabetes, and serum creatinine levels. Carriage of the G allele of PNPLA3 rs738409 plus low ASM% was associated with a higher risk of severe steatosis and presence of liver fibrosis (OR 3.02, 95% CI 1.46–6.26, p = 0.003 and OR 2.18, 95% CI 1.03–4.60, p = 0.041 respectively), and there was a non-significant but borderline increased risk of NASH (OR 2.00, 95% CI 0.98–4.06, p = 0.056).

Conclusions

Low ASM% and the presence of a G allele within PNPLA3 rs738409 is associated with more severe histological features of NAFLD.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

BMI:

Body mass index

ASM%:

Weight-adjusted appendicular skeletal muscle

HOMA-IR:

Homeostasis model assessment-insulin resistance

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

GGT:

γ-Glutamyltranspeptidase

ALP:

Alkaline phosphatase

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

CK-18:

Cytokeratin-18

PNPLA3 :

Patatin-like phospholipase domain-containing 3

NAS:

NAFLD activity score

NASH:

Non-alcoholic steatohepatitis

BIA:

Bioelectrical impedance analyzer

CI:

Confidence interval

NASH-CRN:

NASH-Clinical Research Network

OR:

Odds ratio

References

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73–84

    Article  Google Scholar 

  2. Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther 2012;36:815–823

    Article  CAS  Google Scholar 

  3. Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet 2021;397:2212–2224

    Article  CAS  Google Scholar 

  4. Liu HH, Cao YX, Jin JL, Guo YL, Zhu CG, Wu NQ, et al. Metabolic-associated fatty liver disease and major adverse cardiac events in patients with chronic coronary syndrome: a matched case-control study. Hepatol Int 2021;15:1337–1346

    Article  Google Scholar 

  5. Sun DQ, Jin Y, Wang TY, Zheng KI, Rios RS, Zhang HY, et al. MAFLD and risk of CKD. Metabolism 2021;115: 154433

    Article  CAS  Google Scholar 

  6. Wang TY, Wang RF, Bu ZY, Targher G, Byrne CD, Sun DQ, et al. Association of metabolic dysfunction-associated fatty liver disease with kidney disease. Nat Rev Nephrol 2022;18:259–268

    Article  Google Scholar 

  7. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48:16–31

    Article  Google Scholar 

  8. Sinclair M, Gow PJ, Grossmann M, Angus PW. Review article: sarcopenia in cirrhosis–aetiology, implications and potential therapeutic interventions. Aliment Pharmacol Ther 2016;43:765–777

    Article  CAS  Google Scholar 

  9. Hong HC, Hwang SY, Choi HY, Yoo HJ, Seo JA, Kim SG, et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic obesity study. Hepatology 2014;59:1772–1778

    Article  CAS  Google Scholar 

  10. Lee YH, Kim SU, Song K, Park JY, Kim DY, Ahn SH, et al. Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: nationwide surveys (KNHANES 2008–2011). Hepatology 2016;63:776–786

    Article  CAS  Google Scholar 

  11. Lee YH, Jung KS, Kim SU, Yoon HJ, Yun YJ, Lee BW, et al. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: nationwide surveys (KNHANES 2008–2011). J Hepatol 2015;63:486–493

    Article  Google Scholar 

  12. Koo BK, Kim D, Joo SK, Kim JH, Chang MS, Kim BG, et al. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol 2017;66:123–131

    Article  Google Scholar 

  13. Petta S, Ciminnisi S, Di Marco V, Cabibi D, Camma C, Licata A, et al. Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2017;45:510–518

    Article  CAS  Google Scholar 

  14. Liu Z, Zhang Y, Graham S, Wang X, Cai D, Huang M, et al. Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping. J Hepatol 2020;73:263–276

    Article  CAS  Google Scholar 

  15. Meffert PJ, Repp KD, Volzke H, Weiss FU, Homuth G, Kuhn JP, et al. The PNPLA3 SNP rs738409: G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort. J Hepatol 2018;68:858–860

    Article  CAS  Google Scholar 

  16. Xia MF, Lin HD, Chen LY, Wu L, Ma H, Li Q, et al. The PNPLA3 rs738409 C > G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes. Diabetologia 2019;62:644–654

    Article  CAS  Google Scholar 

  17. Xia MF, Chen LY, Wu L, Ma H, Li Q, Aleteng Q, et al. The PNPLA3 rs738409 C > G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng study. Aliment Pharmacol Ther 2019;50:684–695

    Article  CAS  Google Scholar 

  18. Liu WY, Zheng KI, Pan XY, Ma HL, Zhu PW, Wu XX, et al. Effect of PNPLA3 polymorphism on diagnostic performance of various noninvasive markers for diagnosing and staging nonalcoholic fatty liver disease. J Gastroenterol Hepatol 2020;35:1057–1064

    Article  CAS  Google Scholar 

  19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419

    Article  CAS  Google Scholar 

  20. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321

    Article  Google Scholar 

  21. Brunt EM. Nonalcoholic fatty liver disease: pros and cons of histologic systems of evaluation. Int J Mol Sci 2016;17(1):97

    Article  Google Scholar 

  22. Bhanji RA, Narayanan P, Allen AM, Malhi H, Watt KD. Sarcopenia in hiding: the risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis. Hepatology 2017;66:2055–2065

    Article  CAS  Google Scholar 

  23. Gan D, Wang L, Jia M, Ru Y, Ma Y, Zheng W, et al. Low muscle mass and low muscle strength associate with nonalcoholic fatty liver disease. Clin Nutr 2020;39:1124–1130

    Article  Google Scholar 

  24. Tanaka M, Okada H, Hashimoto Y, Kumagai M, Nishimura H, Oda Y, et al. Relationship between nonalcoholic fatty liver disease and muscle quality as well as quantity evaluated by computed tomography. Liver Int 2020;40:120–130

    Article  Google Scholar 

  25. Pan X, Han Y, Zou T, Zhu G, Xu K, Zheng J, et al. Sarcopenia contributes to the progression of nonalcoholic fatty liver disease- related fibrosis: a meta-analysis. Dig Dis 2018;36:427–436

    Article  Google Scholar 

  26. Seko Y, Mizuno N, Okishio S, Takahashi A, Kataoka S, Okuda K, et al. Clinical and pathological features of sarcopenia-related indices in patients with non-alcoholic fatty liver disease. Hepatol Res 2019;49:627–636

    Article  CAS  Google Scholar 

  27. Shen J, Wong GL, Chan HL, Chan RS, Chan HY, Chu WC, et al. PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease. J Gastroenterol Hepatol 2015;30:139–146

    Article  CAS  Google Scholar 

  28. Lee MJ, Kim EH, Bae SJ, Kim GA, Park SW, Choe J, et al. Age-related decrease in skeletal muscle mass is an independent risk factor for incident nonalcoholic fatty liver disease: a 10-year retrospective cohort study. Gut Liver 2019;13:67–76

    Article  Google Scholar 

  29. Kim G, Lee SE, Lee YB, Jun JE, Ahn J, Bae JC, et al. Relationship between relative skeletal muscle mass and nonalcoholic fatty liver disease: a 7-year longitudinal study. Hepatology 2018;68:1755–1768

    Article  CAS  Google Scholar 

  30. Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, et al. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients: a population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol 2015;110:1306–1314

    Article  CAS  Google Scholar 

  31. Seo DH, Lee YH, Park SW, Choi YJ, Huh BW, Lee E, et al. Sarcopenia is associated with non-alcoholic fatty liver disease in men with type 2 diabetes. Diabetes Metab 2020;46:362–369

    Article  CAS  Google Scholar 

  32. Hashimoto Y, Osaka T, Fukuda T, Tanaka M, Yamazaki M, Fukui M. The relationship between hepatic steatosis and skeletal muscle mass index in men with type 2 diabetes. Endocr J 2016;63:877–884

    Article  CAS  Google Scholar 

  33. Bredella MA. Sex differences in body composition. Adv Exp Med Biol 2017;1043:9–27

    Article  CAS  Google Scholar 

  34. Gheller BJ, Riddle ES, Lem MR, Thalacker-Mercer AE. Understanding age-related changes in skeletal muscle metabolism: differences between females and males. Annu Rev Nutr 2016;36:129–156

    Article  CAS  Google Scholar 

  35. Bosy-Westphal A, Jensen B, Braun W, Pourhassan M, Gallagher D, Muller MJ. Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices. Eur J Clin Nutr 2017;71:1061–1067

    Article  CAS  Google Scholar 

  36. Kuwashiro T, Takahashi H, Hyogo H, Ogawa Y, Imajo K, Yoneda M, et al. Discordant pathological diagnosis of non-alcoholic fatty liver disease: a prospective multicenter study. JGH Open 2020;4:497–502

    Article  Google Scholar 

  37. Leung HH, Puspanathan P, Chan AW, Nik Mustapha NR, Wong VW, Chan WK. Reliability of the nonalcoholic steatohepatitis clinical research network and steatosis activity fibrosis histological scoring systems. J Gastroenterol Hepatol 2022;37(6):1131–1138

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by grants from the National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province and Project of New Century 551 Talent Nurturing in Wenzhou. GT is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. CDB is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK. XYP is supported in part by grants from Wenzhou science and technology Bureau (Y20180141).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Xiao-Yan Pan & Wen-Yue Liu

  2. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Pei-Wu Zhu

  3. NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China

    Gang Li, Liang-Jie Tang, Ou-Yang Huang, Hai-Yang Yuan & Ming-Hua Zheng

  4. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Feng Gao

  5. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Giovanni Targher

  6. Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK

    Christopher D. Byrne

  7. Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK

    Christopher D. Byrne

  8. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China

    Xiao-Dong Wang & Ming-Hua Zheng

  9. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China

    Ming-Hua Zheng

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  1. Xiao-Yan Pan
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Contributions

Guarantor of the article: M-HZ. Authors’ contributions: Study concept and design: X-YP, W-YL and M-HZ. Acquisition of data: P-WZ, GL, L-JT, O-YH, H-YY. Pathology analysis: X-DW. Drafting of the manuscript: X-YP and W-YL. Critical revision and comment: GT and CDB. Statistical analysis: X-YP, W-YL, FG. Study supervision: M-HZ. All authors contributed to the manuscript for important intellectual content and approved the submission.

Corresponding author

Correspondence to Ming-Hua Zheng.

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Conflict of interest

All the authors (Xiao-Yan Pan, Wen-Yue Liu, Pei-Wu Zhu, Gang Li, Liang-Jie Tang, Feng Gao, Ou-Yang Huang, Hai-Yang Yuan, Giovanni Targher, Christopher D. Byrne, Xiao-Dong Wang, Ming-Hua Zheng) declare that they do not have anything to disclose regarding any funding or conflict of interest with respect to this manuscript.

Ethical approval

Ethical approval for the study was obtained from the ethics committee of the First Affiliated Hospital of Wenzhou Medical University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.

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Written informed consent was obtained from all participants included in the study.

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Pan, XY., Liu, WY., Zhu, PW. et al. Low skeletal muscle mass is associated with more severe histological features of non-alcoholic fatty liver disease in male. Hepatol Int 16, 1085–1093 (2022). https://doi.org/10.1007/s12072-022-10384-x

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