Navigating the Maze:  A Mini-Guide for the Management and Therapy of Metabolic Dysfunction-associated Steatotic Liver Disease

Giada Sebastiani; Felice Cinque

doi:10.58931/cpct.2024.2232

Authors

Giada Sebastiani, MD Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
Felice Cinque, MD Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada SC-Medicina Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Department of Pathophysiology and Transplantation, University of Milan, Italy

DOI:

https://doi.org/10.58931/cpct.2024.2232

Abstract

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Nonalcoholic Fatty Liver Disease (NAFLD), poses a significant global health challenge with a prevalence of 30% worldwide. Alarming projections anticipate a substantial increase in MASLD cases, highlighting the urgent need for preparedness and effective policies. The pathophysiology of MASLD involves a complex interplay of metabolic, genetic and lifestyle factors. Although liver biopsy remains the gold standard for the diagnosis of MASLD, non-invasive methods such as abdominal ultrasound, transient elastography with controlled attenuation parameter, shear wave elastography, and non-invasive serum fibrosis scores have been developed and validated. Effective risk stratification in primary care with non-invasive fibrosis scores, such as fibrosis 4 (FIB-4) index and NAFLD fibrosis score (NFS), optimizes healthcare resource utilization, ensuring appropriate referrals for high-risk patients while minimizing unnecessary referrals. Lifestyle intervention, including diet and physical activity, remains the primary therapy for MASLD. Notably, with the FDA approval of resmetirom, the first authorized medication for fibrotic metabolic dysfunction-associated steatohepatitis (MASH), and several antifibrotic agents under investigation, the therapeutic landscape for MASLD is rapidly evolving. Despite its increasing prevalence, morbidity and mortality, MASLD is frequently underdiagnosed in primary care. In this review, we aim to provide primary care physicians an update on the diagnosis, management and treatment
of MASLD.

Author Biographies

Giada Sebastiani, MD, Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada

Giada Sebastiani is Professor of Medicine in the Division of Gastroenterology and Hepatology at McGill University. She received a medical degree and specialized in internal medicine at the University of Padua, Italy. She had research training at Harvard Medical School (US), University College of London (UK), University of Bordeaux (France). Her work focuses on steatotic liver disease (MASLD), liver fibrosis and non-invasive diagnostic tools in liver disease. She is author of 170 articles in peer-reviewed journals (including Nature Reviews Gastroenterology & Hepatology, Lancet Gastroenterology and Hepatology, Lancet Digital Health, Gastroenterology, Hepatology, Journal of Hepatology, Clinical Infectious Diseases; h-index=46, citations>9,500), 13 book chapters, 275 conference publications. Dr Sebastiani is the 2024 President Elect of the Canadian Association for the Study of the Liver. She is co-founder of the Canadian NASH Network and panel member in the Consensus on Models of Care in MASLD of the International Liver Foundation. She is the sole North American representative in the guidelines of the European AIDS Clinical Society as panel member of the Liver Group. Dr Sebastiani was awarded the prestigious Senior Clinical Research Salary Award from Fonds Recherche Sante Quebec. Her research program is funded by the Canadian Institute for Health Research, the Fonds Recherche Sante Quebec, the CIHR Canadian HIV Trials Network, Crohn’s Colitis Canada.

Felice Cinque, MD, Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada SC-Medicina Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Department of Pathophysiology and Transplantation, University of Milan, Italy

Dr. Felice Cinque is a clinician-scientist currently enrolled in the last year of internal medicine residency and the first year of the PhD program in clinical research at the University of Milan. He completed a research fellowship at McGill University in the Division of Gastroenterology and Hepatology and Infectious Diseases in 2023. His work focuses on chronic liver disease, MASLD in vulnerable populations such as people living with HIV and people with diabetes, with a focus on patient-centered care. He is also an advocate for the inclusion of the LGBTQ+ community in medicine and research.

References

Younossi ZM, Golabi P, Paik JM et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatol. 2023 Apr;77(4):1335–47. DOI: https://doi.org/10.1097/HEP.0000000000000004

Swain MG, Ramji A, Patel K et al. Burden of nonalcoholic fatty liver disease in Canada, 2019-2030: a modelling study. CMAJ Open. 2020;8(2):E429–36. DOI: https://doi.org/10.9778/cmajo.20190212

Lazarus JV, Mark HE, Villota-Rivas M et al. The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge? J Hepatol. 2022 Apr;76(4):771–80.

Rinella ME, Lazarus JV, Ratziu V et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatol. 2023 Jun 24; DOI: https://doi.org/10.1097/HEP.0000000000000696

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May;77(5):1797–835. DOI: https://doi.org/10.1097/HEP.0000000000000323

Adams LA, Anstee QM, Tilg H et al. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017 Jun 1;66(6):1138–53. DOI: https://doi.org/10.1136/gutjnl-2017-313884

Allen AM, Van Houten HK, Sangaralingham LR et al. Healthcare cost and utilization in nonalcoholic fatty liver disease. Real-world data from a large US claims database. Hepatol. 2018 Dec;68(6):2230–8. DOI: https://doi.org/10.1002/hep.30094

Schreiner AD, Sattar N. Identifying patients with nonalcoholic fatty liver disease in primary care: how and for what benefit? J Clin Med. 2023 Jun 12;12(12):4001. DOI: https://doi.org/10.3390/jcm12124001

Tilg H, Adolph TE, Moschen AR. Multiple parallel hits hypothesis in nonalcoholic fatty liver disease: revisited after a decade. Hepatology. 2021 Feb;73(2):833–42. DOI: https://doi.org/10.1002/hep.31518

Bugianesi E, Moscatiello S, Ciaravella MF et al. Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des. 16(17):1941–51. DOI: https://doi.org/10.2174/138161210791208875

Saponaro C, Sabatini S, Gaggini M et al. Adipose tissue dysfunction and visceral fat are associated with hepatic insulin resistance and severity of NASH even in lean individuals. Liver Int. 2022;42(11):2418–27. DOI: https://doi.org/10.1111/liv.15377

Hrncir T, Hrncirova L, Kverka M et al. Gut microbiota and NAFLD: pathogenetic mechanisms, microbiota signatures, and therapeutic interventions. Microorganisms. 2021 Apr 29;9(5):957. DOI: https://doi.org/10.3390/microorganisms9050957

Sharma D, Mandal P. NAFLD: genetics and its clinical implications. Clin Res Hepatol Gastroenterol. 2022 Nov;46(9):102003. DOI: https://doi.org/10.1016/j.clinre.2022.102003

Cinque F, Cespiati A, Lombardi R et al. Nutritional and lifestyle therapy for NAFLD in people with HIV. Nutrients. 2023 Apr 20;15(8):1990. DOI: https://doi.org/10.3390/nu15081990

Berzigotti A, Tsochatzis E, Boursier J et al. EASL clinical practice guidelines on non -invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatol. 2021 Sep;75(3):659–89. DOI: https://doi.org/10.1016/j.jhep.2021.05.025

Dulai PS, Singh S, Patel J et al. Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis. Hepatol. 2017 May;65(5):1557–65. DOI: https://doi.org/10.1002/hep.29085

ElSayed NA, Aleppo G, Aroda VR et al. Comprehensive medical evaluation and assessment of comorbidities: standards of care in diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S49–67. DOI: https://doi.org/10.2337/dc23-S004

Pugliese N, Plaz Torres MC, Petta S et al. Is there an ‘ideal’ diet for patients with NAFLD? Eur J Clin Invest [Internet]. 2022 Mar [cited 2023 Feb 4];52(3). Available from: https://onlinelibrary.wiley.com/doi/10.1111/eci.13659 DOI: https://doi.org/10.1111/eci.13659

Bull FC, Al-Ansari SS, Biddle S et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020 Dec;54(24):1451–62. DOI: https://doi.org/10.1136/bjsports-2020-102955

Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024 Feb 8;390(6):497–509. DOI: https://doi.org/10.1056/NEJMoa2309000

Navigating the Maze: A Mini-Guide for the Management and Therapy of Metabolic Dysfunction-associated Steatotic Liver Disease

Authors

DOI:

Abstract

Author Biographies

Giada Sebastiani, MD, Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada

References

Downloads

Published

How to Cite

Issue

Section

License

Summary

Open Access

Licence