An international multidisciplinary consensus statement on MAFLD and the risk of CVD (original) (raw)

Abstract

Background

Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25–30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.

Methods and results

A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.

Conculsions

The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

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Data availability

All data included in this study are available upon request by contact with the corresponding author (zhengmh@wmu.edu.cn).

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Acknowledgements

The authors thank two Delphi study methodologists Prof. Joey S.W. Kwong (St. Luke's International University, Japan) and Prof. Zubing Mei (Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China) for methodological assistance. Seung Up Kim, Vincent Wai-Sun Wong, Mohammed Eslam, Yusuf Yilmaz, Wah Kheong Chan, Sombat Treeprasertsuk, Hasmik Ghazinyan, Jian-Gao Fan, George Boon-Bee Goh, Saeed Hamid, Jacob George and Ming-Hua Zheng are members of the APASL MAIDEN.

Funding

The authors have not disclosed any funding.

Author information

Author notes

1. Xiao-Dong Zhou, Giovanni Targher and Christopher D. Byrne are co-first authors.

Authors and Affiliations

1. Department of Cardiovascular Medicine, The Heart Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
   Xiao-Dong Zhou
2. Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy
   Giovanni Targher
3. Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, and University of Southampton, Southampton General Hospital, Southampton, UK
   Christopher D. Byrne
4. Department of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, USA
   Virend Somers & C. Anwar A. Chahal
5. Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
   Seung Up Kim
6. Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, PA, USA
   C. Anwar A. Chahal
7. Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, London, EC1A 7BE, West Smithfield, UK
   C. Anwar A. Chahal
8. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
   Vincent Wai-Sun Wong
9. Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
   Jingjing Cai
10. Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
    Michael D. Shapiro
11. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, 2145, Australia
    Mohammed Eslam & Jacob George
12. Université Paris -Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France
    Philippe Gabriel Steg
13. Department of Internal Medicine, Division of Cardiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
    Ki-Chul Sung
14. Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, National Diabetes Obesity and Cholesterol Foundation and Diabetes Foundation (India), New Delhi, India
    Anoop Misra
15. State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Jian-Jun Li
16. Biomedical Research Institute Sant Pau (IIB Sant Pau), Sardenya Primary Health Care Center, Barcelona, Spain
    Carlos Brotons
17. Department of Cardiology, Shunde Hospital, Southern Medical University, Jiazi Road, Lunjiao Town, Shunde District, Foshan, China
    Yuli Huang
18. Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
    George V. Papatheodoridis
19. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
    Aijun Sun
20. Institute of Gastroenterology, Marmara University, Istanbul, Turkey
    Yusuf Yilmaz
21. Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
    Yusuf Yilmaz
22. Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
    Wah Kheong Chan
23. Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, 3025 Shennan Middle Road, Shenzhen, China
    Hui Huang
24. Liver Research Unit, Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
    Nahum Méndez-Sánchez
25. Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
    Saleh A. Alqahtani
26. Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, USA
    Saleh A. Alqahtani
27. Laboratório de Nutrição e Metabolismo, Faculdade de Medicina, Clínica Universitária de Gastrenterologia, Universidade de Lisboa, Lisbon, Portugal
    Helena Cortez-Pinto
28. Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, UK
    Gregory Y. H. Lip
29. Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
    Gregory Y. H. Lip
30. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 206, Rotterdam, The Netherlands
    Robert J. de Knegt
31. Department of Internal Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
    Ponsiano Ocama
32. Department of Digestive and Liver Diseases, Institute of Biomedicine of Seville, University Hospital Virgen del Rocio, University of Seville, Seville, Spain
    Manuel Romero-Gomez
33. Department of Cardiology, Duke University School of Medicine, Durham, NC, USA
    Marat Fudim
34. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
    Marat Fudim
35. Division of Gastroenterology and Hepatology, Chronic Viral Illness Service, McGill University Health Centre, Royal Victoria Hospital, 1001 Blvd. Décarie, Montreal, Canada
    Giada Sebastiani
36. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
    Jang Won Son
37. Department of Hepatology, RCSI School of Medicine and Medical Sciences, Dublin/Beaumont Hospital, Dublin, Ireland
    John D. Ryan
38. Preventive Cardiology Laboratory and Cardiometabolic Clinic, Second Cardiology Department, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
    Ignatios Ikonomidis
39. Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
    Sombat Treeprasertsuk
40. Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
    Daniele Pastori
41. Department of Medical Imaging, “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepathology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
    Monica Lupsor-Platon
42. Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
    Herbert Tilg
43. Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
    Hasmik Ghazinyan
44. Hepato-Gastroenterology Department, University Hospital, 4 Larrey Street, 49933, Angers Cedex 09, France
    Jerome Boursier
45. HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France
    Jerome Boursier
46. Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, Japan
    Masahide Hamaguchi
47. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
    Mindie H. Nguyen
48. Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
    Mindie H. Nguyen
49. Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Jian-Gao Fan
50. Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
    George Boon-Bee Goh
51. Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
    Mamun Al Mahtab
52. Department of Medicine, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan
    Saeed Hamid
53. Department of Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
    Nilanka Perera
54. MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China
    Ming-Hua Zheng
55. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
    Ming-Hua Zheng
56. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
    Ming-Hua Zheng

Authors

1. Xiao-Dong Zhou
2. Giovanni Targher
3. Christopher D. Byrne
4. Virend Somers
5. Seung Up Kim
6. C. Anwar A. Chahal
7. Vincent Wai-Sun Wong
8. Jingjing Cai
9. Michael D. Shapiro
10. Mohammed Eslam
11. Philippe Gabriel Steg
12. Ki-Chul Sung
13. Anoop Misra
14. Jian-Jun Li
15. Carlos Brotons
16. Yuli Huang
17. George V. Papatheodoridis
18. Aijun Sun
19. Yusuf Yilmaz
20. Wah Kheong Chan
21. Hui Huang
22. Nahum Méndez-Sánchez
23. Saleh A. Alqahtani
24. Helena Cortez-Pinto
25. Gregory Y. H. Lip
26. Robert J. de Knegt
27. Ponsiano Ocama
28. Manuel Romero-Gomez
29. Marat Fudim
30. Giada Sebastiani
31. Jang Won Son
32. John D. Ryan
33. Ignatios Ikonomidis
34. Sombat Treeprasertsuk
35. Daniele Pastori
36. Monica Lupsor-Platon
37. Herbert Tilg
38. Hasmik Ghazinyan
39. Jerome Boursier
40. Masahide Hamaguchi
41. Mindie H. Nguyen
42. Jian-Gao Fan
43. George Boon-Bee Goh
44. Mamun Al Mahtab
45. Saeed Hamid
46. Nilanka Perera
47. Jacob George
48. Ming-Hua Zheng

Contributions

Design the study, Participate the Delphi study, Review the data and draft the statement, Review the full draft: X-DZ, GT, CDB. Participate the Delphi study: X-DZ, GT, CDB, MDS, SUK, CAAC, JC, VKS, MH, PGS, K-CS, AM, VW-SW, J-JL, J-GF, CB, YH, GVP, AS, YY, WKC, HH, NM-S, SAA, HC-P, GYHL, RJK, PO, MR-G, ST, GS, JWS, JDR, II, MF, DP, ML-P, HT, HG, JB, ME, MHN, GB-BG, MAM, SH, NP, JG, M-HZ. Review the data and draft the statement: X-DZ, GT, JG, M-HZ. Review the full draft: X-DZ, GT, CDB, MDS, SUK, C. AAC, JC, VKS, MH, PGS, Ki-Chul Sung, AM, VW-SW, J-JL, J-GF, CB, YH, GVP, AS, YY, WKC, HH, NM-S, SAA, HC-P, GYHL, RJK, PO, MR-G, ST, GS, JWS, JDR, II, MF, DP, ML-P, HT, HG, JB. ME, MHN, GB-BG, MAM, SH, NP, JG, M-HZ.

Corresponding authors

Correspondence toJacob George or Ming-Hua Zheng.

Ethics declarations

Conflict of interest

George V Papatheodoridis: Advisor: Abbvie, Albireo, Amgen, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche and Takeda; Lectures: Abbvie, Gilead, GlaxoSmithKline, Ipsen, Novo Nordisk, Sobi; Research grants: Abbvie, Gilead; Investigator in clinical trials: Abbvie, Astellas, Bayer, Eiger, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Noorik, Novartis, Novo Nordisk, Regulus, Roche, Takeda. Giada Sebastiani: Speaker: Merck, Gilead, Abbvie, Novonordisk, Novartis and Pfizer; Advisory board member: Pfizer, Merck, Novonordisk, Gilead and Intercept; Unrestricted research funding: Theratecnologies Inc. Gregory Y. H. Lip: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthem. No fees are received personally. GYHL is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871. Jian-Gao Fan: Speaker, a consultant and an advisory for Sanofi, Abbott, EchoSens, Novartis, Hisky, Gilead, Allergan, Terns and MADAUS GMBH. John D. Ryan: None related to MAFLD. Consulting: Bond Biosciences, Pfizer, Gilead; Lectures: Kyowa kirin, Falk. Marat Fudim: Dr Fudim was supported by Bayer. He receives consulting fees from Bayer, Merck, NovoNordisk. Michael D. Shapiro: Research Grants (paid to my institution): AHA, NIH, Amgen, Novartis, Ionis, Esperion; Consultant: Ionis, Novartis, Regeneron; Scientific Advisory Boards: Amgen, Novartis, Precision Bioscience. Mindie H. Nguyen: Last 36 months: Research support: Pfizer, Enanta, Astra Zeneca, Innogen, Exact Science, CurveBio, Delfi Biotech, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation. Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, Exelixis Research grants. Ming-Hua Zheng: Lectures: Hisky Medical. Philippe Gabriel Steg: Research grants: Amarin, Bayer, Sanofi, and Servier; Clinical Trials (Steering committee, CEC, DSMB): Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier; Consulting or speaking: Amarin, Amgen, BMS/Myokardia, Merck, Novo-Nordisk, Regeneron; Senior Associate Editor at Circulation. Seung Up Kim: He has served as an advisory committee member Gilead Sciences, Bayer, Eisai, and Novo Nordisk. He is a speaker for Gilead Sciences, GSK, Bayer, Eisai, Abbvie, EchoSens, MSD, Eisai, Otsuka, and Bristol-Myers Squibb. He has also received a research grant from Abbvie and Bristol-Myers Squibb. Vincent Wai-Sun Wong: Consultancy: AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions; Lectures: Abbott, AbbVie, Gilead Sciences, Novo Nordisk; Research grants: Gilead Sciences; Stock: Co-founder of Illuminatio Medical Technology Limited. Wah Kheong Chan: Consultant or advisory board member for Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; speaker for Viatris and Hisky Medical. Yusuf Yilmaz: He has served as consultant to Cymabay, Zydus, Novo Nordisk, and Echosens. The other authors have no conflicts of interest to declare.

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Zhou, XD., Targher, G., Byrne, C.D. et al. An international multidisciplinary consensus statement on MAFLD and the risk of CVD.Hepatol Int 17, 773–791 (2023). https://doi.org/10.1007/s12072-023-10543-8

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• Received: 19 March 2023
• Accepted: 18 April 2023
• Published: 19 May 2023
• Version of record: 19 May 2023
• Issue date: August 2023
• DOI: https://doi.org/10.1007/s12072-023-10543-8

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