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Steatotic liver disease — Clinical Guidelines

Overview

Steatotic liver disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), encompasses conditions characterized by hepatic fat accumulation in the presence of cardiometabolic risk factors, often linked to obesity and type 2 diabetes 7 8 9.

Diagnosis

Key Diagnostic Criteria: Presence of hepatic steatosis with one or more cardiometabolic risk factors (e.g., obesity, insulin resistance, dyslipidemia) 7 8 9.

Recommended Tests:

- Liver function tests (ALT, AST, ALP, GGT) 7. - Imaging (ultrasound, MRI-PDFF, CT) for steatosis grading 26. - Laboratory assessment for cardiometabolic risk factors (fasting lipids, glucose, HbA1c) 1 7.

Grading:

- Steatosis graded by imaging (mild, moderate, severe) 26. - Advanced fibrosis assessed via non-invasive tests (FIB-4, ELF score) 7.

Management

First-Line Treatments:

- Lifestyle modifications (diet, exercise, weight loss) 7 4 5. - Management of underlying cardiometabolic risk factors (e.g., glycemic control, lipid management) 1 7.

Adjunctive Treatments:

- Lipid-Lowering Agents: - Statins for cardiovascular risk reduction 1 7. - Novel agents like volanesorsen for severe hypertriglyceridemia 10 13. - Apolipoprotein C-III inhibitors (e.g., volanesorsen) for severe hypertriglyceridemia 10 13. - Other Therapies: - Vitamin D supplementation based on deficiency status 15 16. - Consideration of personalized genome-scale metabolic models for targeted interventions 23.

Special Populations

Pediatrics: Hypertriglyceridemia affects 10-20% of children and adolescents, often linked to obesity and insulin resistance 1.

Comorbidities: Hypertriglyceridemia is associated with increased cardiovascular risk and can complicate conditions like periodontitis 2 and chronic hepatitis B 15.

Key Recommendations

Screen and manage cardiometabolic risk factors to prevent progression of MASLD (Evidence: Strong 7).

Implement lifestyle modifications as the cornerstone of treatment for MASLD (Evidence: Strong 7 4 5).

Use novel lipid-lowering agents such as apolipoprotein C-III inhibitors for severe hypertriglyceridemia (Evidence: Moderate 10 13).

Assess and correct vitamin D deficiency in patients with MASLD, given its potential impact on disease severity (Evidence: Moderate 15 16).

Monitor and manage polypharmacy carefully to avoid adverse interactions in patients with multiple comorbidities (Evidence: Moderate 6).

References

1 Peterson AL, Ashraf AP, Bachman J, Hegele RA, Rashad M, South AM et al.. Screening, Diagnosis, and Management of Pediatric Hypertriglyceridemia: A Scientific Statement From the American Heart Association. Arteriosclerosis, thrombosis, and vascular biology 2026. link 2 Mousa N, Elmetwalli A, Abdel-Razik A, Mousa E, Abdelsalam M, Elbaz S et al.. Periodontitis and Metabolic Dysfunction-Associated Steatotic Liver Disease: emphasizing the clinical interplay between hepatologists and dentists. Odontology 2026. link 3 Alqahtani SA, Yilmaz Y, El-Kassas M, Alswat K, Mawardi M, Sanai FM et al.. Knowledge about metabolic dysfunction-associated steatotic liver disease among the medical professionals from countries in the MENA region. Annals of hepatology 2025. link 4 Abdulrazzak E, Alabdul Razzak I, Noureddin M, Trivedi HD. A Gastroenterologist's Approach to Improving Metabolic Health in MASLD. Journal of clinical gastroenterology 2025. link 5 Sebastiani G, Raggi P, Guaraldi G. Integrating the Care of Metabolic Dysfunction-associated Steatotic Liver Disease Into Cardiac Rehabilitation: A Multisystem Approach. The Canadian journal of cardiology 2025. link 6 Neuschwander-Tetri BA, Morris HL, Mospan AR, Yu F, Munoz B, Abraham S et al.. The Magnitude of Polypharmacy and Role of Disease Severity and Patient Sex in Medication Use Among Patients With MASLD Enrolled in TARGET-NASH. Alimentary pharmacology & therapeutics 2025. link 7 . EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obesity facts 2024. link 8 . EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of hepatology 2024. link 9 . EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive Summary. Diabetologia 2024. link 10 Wierzbicki AS. Novel agents for treating severe hypertriglyceridemia. Med (New York, N.Y.) 2024. link 11 Osonoi S, Takebe T. Organoid-guided precision hepatology for metabolic liver disease. Journal of hepatology 2024. link 12 Tan HLE, Hure A, Peel R, Hancock S, Attia J. Prevalence and clinical risk prediction of hypertriglyceridaemia in a community cohort. Internal medicine journal 2023. link 13 Calcaterra I, Lupoli R, Di Minno A, Di Minno MND. Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials. European journal of clinical investigation 2022. link 14 VanHook AM. (no title). Science signaling 2022. link 15 Luo L, Ye J, Shao C, Lin Y, Sun Y, Feng S et al.. Vitamin D Status Presents Different Relationships with Severity in Metabolic-Associated Fatty Liver Disease Patients with or without Hepatitis B Infection. Nutrients 2022. link 16 Guan Y, Xu Y, Su H, Sun X, Li Y, Wang T. Effect of serum vitamin D on metabolic associated fatty liver disease: a large population-based study. Scandinavian journal of gastroenterology 2022. link 17 Brotons C, Moral I, González J, Fernández D, Puig M, Vilella MT. Epidemiology of hypertriglyceridaemia. Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis 2021. link 18 Clark H, Schulte R, Haggstrom AN. Severe hypertriglyceridemia following sirolimus use in an infant. Pediatric dermatology 2021. link 19 Raza Z, Mulki AK, Garufi LC, Greenberg GM. Hypertriglyceridemia: A strategic approach. The Journal of family practice 2020. link 20 Ghoor S, Berlyn P, Brey N. Exchange transfusions for extreme hypertriglyceridemia in a 7-week-old infant with multi-organ failure. Journal of clinical lipidology 2018. link 21 Kersten S. Triglyceride Metabolism under Attack. Cell metabolism 2017. link 22 Wong W. New connections: New targets for fighting hepatic steatosis. Science signaling 2017. link 23 Miller MA. Richer data with personalized GEMs. Science translational medicine 2017. link 24 Argula RG, Strange C, Budisavljevic MN. Multiorgan system dysfunction in the chylomicronemia syndrome. Journal of intensive care medicine 2014. link 25 Cybulska B, Kłosiewicz-Latoszek L. Management of severe hypertriglyceridaemia. Kardiologia polska 2013. link 26 El-Badry AM, Breitenstein S, Jochum W, Washington K, Paradis V, Rubbia-Brandt L et al.. Assessment of hepatic steatosis by expert pathologists: the end of a gold standard. Annals of surgery 2009. link 27 Capell WH, Eckel RH. Treatment of hypertriglyceridemia. Current diabetes reports 2006. link 28 Inoue I, Koh HS, Mizotani K, Goto S, Tanaka K, Yagasaki F et al.. A patient with severe hypertriglyceridemia associated with anemia and hypoalbuminemia. Journal of atherosclerosis and thrombosis 2003. link 29 Mustafa G, Khan PA, Azam M, Rabbani W, Ali Q. Hypertriglyceridemia in pediatrics. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 2003. link 30 Gomber S, Kela K, Abdul Rahiman CL. Hypertriglyceridaemia-thalassaemia syndrome. Annals of tropical paediatrics 1996. link 31 Warwas M, Gburek J, Osada J, Gołab K. Purification and characterization of cystatin from duck egg white. Acta biochimica Polonica 1995. link 32 Salmonson EC, Lundstedt C, Holmin T, Hägerstrand I. Focal periportal liver steatosis. Abdominal imaging 1993. link 33 Crowe MJ, Gross DJ. Eruptive xanthoma. Cutis 1992. link 34 Rais N, Undre AR, Shah A. Cholelithiasis and endogenous hypertriglyceridemia in a thirteen year old girl (a case report). Journal of postgraduate medicine 1991. link 35 Knutsson A. Relationships between serum triglycerides and gamma-glutamyltransferase among shift and day workers. Journal of internal medicine 1989. link 36 Leaf DA. Triglycerides. Are they important?. Postgraduate medicine 1988. link 37 Weisweiler P, Schwandt P. Immunonephelometric quantitation of apolipoprotein E in human serum. Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie 1983. link 38 Rubba P. Fractional fatty acid incorporation into human adipose tissue (FIAT) in hypertriglyceridemia. Atherosclerosis 1978. link90091-6) 39 Vrána A, Poledne R, Fábry P, Kazdová L. Palmitate and glucose oxidation by diaphragm of rats with fructose-induced hypertriglyceridemia. Metabolism: clinical and experimental 1978. link90131-2) 40 Camarri E, Marcolongo R, Fici F. Hypotriglyceridemic effect of chenodeoxycholic acid after a short time of administration. International journal of clinical pharmacology and biopharmacy 1978. link

Steatotic liver disease