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Obesity & Liver Health

Who should be screened for MASLD/MASH?

To enable early intervention, clinical guidelines recommend targeted case-finding in high-risk individuals to facilitate early diagnosis and identification of advanced fibrosis.1,2  

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Screen people with
Screen people with

Early identification and management of MASLD/MASH is essential and can be straightforward, even though the condition is often asymptomatic, with few or non-specific symptoms during its early stages.3

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Early identification and management of MASLD/MASH has numerous benefits, most notably the potential to slow or reverse disease progression and improve outcomes.4,5
Benefits of early MASLD/MASH diagnosis
Benefits of early MASLD/MASH diagnosis

MASH, metabolic dysfunction-associated steatohepatitis.

Symptoms are generally subtle and often attributed to identifiable conditions, such as obesity and type 2 diabetes (T2D). This makes it difficult for physicians and people living with MASLD/MASH to identify symptoms and establish their underlying cause.3

MASH symptoms
MASH symptoms

MASH, metabolic dysfunction-associated steatohepatitis.

As a result, individuals with MASH are often diagnosed at advanced stages – such as cirrhosis or hepatocellular carcinoma (HCC) – when symptoms have worsened and irreversible liver damage has already occurred.6-8

Consequences of late diagnosis

The critical need for early detection and proactive management of MASH is underscored by the consequences of late diagnosis.9 Delaying the diagnosis of MASH results in increased morbidity and mortality for people living with the disease, as well as significant socioeconomic costs associated with treatment of advanced stages.10

Clinical and economic impacts of MASH
Clinical and economic impacts of MASH

MASH, metabolic dysfunction-associated steatohepatitis; QoL, quality of life.

Progressive liver damage also has a deleterious impact on overall quality of life (QoL) and general health status, with these negative effects present even early in the course of the disease.11

Given the serious consequences of disease progression, early intervention could prevent the development of irreversible liver damage, lower the risk of cirrhosis, and reduce the burden of cardiometabolic disease.5,8

What tools are available to help diagnose MASLD/MASH?

Before a definitive diagnosis can be made, it is essential to rule out other causes of liver disease, e.g. viral infection or alcohol use disorder.14

Traditionally, liver biopsy has been the gold standard for MASH diagnosis and disease staging, but it has limitations that result in it being underused.1,2

Limitations and potential complications of liver biopsy15,16

Limitations and potential complications of liver biopsy
Limitations and potential complications of liver biopsy

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Non-invasive tests, also known as NITs, are simple, repeatable diagnostic tools used to predict the presence of fibrosis.1,17 They are increasingly being adopted as an alternative to liver biopsy to enable broader screening and diagnosis, in order to identify and manage MASH earlier in its disease course.18,19

Several NITs can be used to detect fibrosis – these can be blood-based, imaging-based, or a combination of both.

Blood-based tests2,14,20-25

Blood-based tests
Blood-based tests

*Reference ranges for GGT and ALP may vary between laboratories; always refer to local guidelines.

Imaging-based tests2,14,26-30

Imaging-based tests
Imaging-based tests

Combined tests2,14

Combined tests
Combined tests

ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; CAP, controlled attenuation parameter; ELF™, enhanced liver fibrosis; F, fibrosis stage; FIB-4, fibrosis-4; GGT, gamma-glutamyl transferase; HA, hyaluronic acid; LSM, liver stiffness measurement; MASH, metabolic dysfunction-associated steatohepatitis; MRE, magnetic resonance elastography; MRI-PDFF, magnetic resonance imaging-derived proton density fat fraction; PIIINP, N-terminal peptide of type III procollagen; Pro-C3, N-terminal type III collagen propeptide; TIMP-1, TIMP metallopeptidase inhibitor 1; VCTE, vibration‑controlled transient elastography. 

Facilitating early MASH diagnosis: Professor Laurent Castera explores non-invasive testing

FIB-4: A first-line approach

FIB-4 is one of the most well-established and accessible NITs for assessing liver fibrosis.1 It can monitor disease progression and serves as an independent predictor of all-cause mortality and liver-related adverse outcomes.31

Calculating the FIB-4 score1

Calculating the FIB-4 score
Calculating the FIB-4 score

ALT, alanine transaminase; AST, aspartate transaminase; FIB-4, fibrosis-4.

FIB-4 in primary care

FIB-4 is the preferred first-line NIT in primary care because it:20,32

  • uses readily available clinical parameters

  • can be automatically calculated

  • has good sensitivity for advanced fibrosis (F3–F4)

Following an initial FIB-4 screening, a coordinated approach is essential to identify high-risk individuals early. These individuals should then be referred to specialist care for further assessment:33

FIB-4 in primary care
FIB-4 in primary care

Case-finding algorithm based on/adapted from the Global Consensus Recommendations for MASLD/Steatohepatitis, Younossi ZM, et al, 2025.33 The checklist is intended for case-finding, which targets high-risk patients, rather than general population screening.

*Assess alcohol intake for all patients.

FIB-4, fibrosis-4; MASH, metabolic dysfunction-associated steatohepatitis; T2D, type 2 diabetes; VCTE, vibration-controlled transient elastography.

NITs can be used to monitor disease progression by predicting histology and liver-related outcomes:34

Combining NITs
Combining NITs

ELF™, enhanced liver fibrosis; FDA, US food and drug administration; FIB-4, fibrosis-4; LSM, liver stiffness measurement; MALO, major adverse liver outcome; MRE, magnetic resonance elastography; NIT, non-invasive test; NPV, negative predictive value.

Preferably, more than one non-invasive test should be used to identify patients likely to have stage 2 or 3 fibrosis, as multiple sequential NITs can provide a more accurate risk assessment than a single test.32,35 In line with UK British Society of Gastroenterology (BSG) recommendations, a two‑step pathway using FIB‑4 for initial risk stratification followed by the ELF™ test in patients with indeterminate or high‑risk results can help reduce unnecessary referrals to secondary care and improve identification of patients with advanced fibrosis.37

Although NITs have proven clinical utility, there are limitations that should be considered when using in routine practice.37

Limitations of non-invasive tests37-39

NITs: Limitations
NITs: Limitations

ELF™, enhanced liver fibrosis; MRE, magnetic resonance elastography; Pro-C3, N-terminal type III collagen propeptide.

Disease staging in MASLD/MASH – why does it matter?

There are five stages of liver fibrosis in MASLD (F0–F4), which represent the severity of the disease.40,41

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Five stages of liver fibrosis
Five stages of liver fibrosis

F, fibrosis stage; HCC, hepatocellular carcinoma; MASH, metabolic dysfunction-associated steatohepatitis; MASL, metabolic dysfunction-associated steatotic liver; MASLD, metabolic dysfunction-associated steatotic liver disease.

Patients with MASLD may be asymptomatic or have non-specific symptoms in the early stages (F0–F3), during which liver fibrosis progresses gradually. However, once MASH progresses to F4 cirrhosis, prognosis deteriorates rapidly.13,42 MASH may progress to more advanced liver disease states, in which liver-related mortality is higher than other causes of death.13

Cirrhosis development43

Cirrhosis development
Cirrhosis development

F, fibrosis stage; MASH, metabolic dysfunction-associated steatohepatitis.

The progression of fibrosis is associated with a higher mortality rate and increased healthcare costs and patient burden.40,44 Therefore, it is crucial to detect and treat MASH early to prevent long-term complications and improve patient outcomes.45

liver health

Understanding MASLD/MASH

 
Back to understanding MASLD/MASH

obesity & mash

Intertwined Epidemics

 
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  2. Rinella ME, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797-1835.

  3. Eskridge W, et al. Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective. J Clin Med. 2023;12:6216.

  4. Targher G, et al. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. Gut. 2024;73:691-702.

  5. Sandireddy R, et al. Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases. Front Cell Dev Biol. 2024;12:1433857.

  6. Povsic M, et al. A Structured Literature Review of the Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH). Adv Ther. 2019;36:1574-1594.

  7. Younossi ZM, et al. Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH. Hepatol Commun. 2024;8:e0488.

  8. Alkhouri N, Noureddin M. Management strategies for metabolic dysfunction-associated steatotic liver disease (MASLD). Am J Manag Care. 2024;30:S159-S174.

  9. Heyens LJM, et al. Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment. Front Med (Lausanne). 2021;8:615978.

  10. Boursier J, et al. Hospitalization costs and risk of mortality in adults with nonalcoholic steatohepatitis: analysis of a French national hospital database. EClinicalMedicine. 2020;25:100445.

  11. Younossi Z, et al. The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes. JHEP Rep. 2022;4:100525.

  12. Davidson JA, et al. Estimating the clinical and healthcare burden of metabolic dysfunction-associated steatohepatitis in England: a retrospective cohort study using routinely collected healthcare data from 2011 to 2020. BMJ Open 2025;15:e095761

  13. Luthra R, Sheth A. Understanding MASH: An examination of progression and clinical outcomes by disease severity in the TARGET-NASH database. Adv Ther. 2025;42:1165-1195.

  14. 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.

  15. Hudson D, et al. Modernizing metabolic dysfunction-associated steatotic liver disease diagnostics: the progressive shift from liver biopsy to noninvasive techniques. Ther Adv Gastroenterol. 2024;17:17562848241276334.

  16. Harrison SA, Dubourg J. Liver biopsy evaluation in MASH drug development: Think thrice, act wise. J Hepatol. 2024;81:886-894.

  17. Angulo P, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846-854.

  18. Tagliaferro M, et al. New biomarkers in liver fibrosis: A pass through the quicksand? J Pers Med. 2024;14:798.

  19. Gbadamosi SO, et al. Noninvasive tests and diagnostic pathways to MASH diagnosis in the United States: a retrospective observational study. J Med Econ. 2025;28:314-322.

  20. Newsome PN, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67:6-19.

  21. Kalas MA, et al. Abnormal liver enzymes: A review for clinicians. World J Hepatol. 2021;13:1688-1698.

  22. Health Matters. AST:ALT Ratio. 2025. Available at: https://healthmatters.io/understand-blood-test-results/ast-alt-ratio. Last accessed: May 2026.

  23. Nielsen MJ, et al. PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Rep. 2023;5:100743.

  24. Lichtinghagen R, et al. The Enhanced Liver Fibrosis (ELF) score: normal values, influence factors and proposed cut-off values. J Hepatol. 2013;59:236-242.

  25. Vroon DH, Israili Z. Alkaline phosphatase and gamma glutamyltransferase. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 100.

  26. Oeda S, et al. Diagnostic accuracy of FibroScan and factors affecting measurements. Diagnostics (Basel). 2020;10.(11):940.

  27. Caussy C, et al. Noninvasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. Hepatology. 2018;68:763-772.

  28. Rodge GA, et al. Quantification of liver fat by MRI-PDFF imaging in patients with suspected non-alcoholic fatty liver disease and its correlation with metabolic syndrome, liver function test and ultrasonography. J Clin Exp Hepatol. 2021;11:586-591.

  29. Huber A, et al. State-of-the-art imaging of liver fibrosis and cirrhosis: A comprehensive review of current applications and future perspectives. Eur J Radiol Open. 2015;2:90-100.

  30. Jalil S, Pagadala M, Dunn N, Blaney H, Elfeki M, Thakral N, Singal AK. Transient Elastography and Fibroscan: Stethoscope of a Hepatologist in Today's World. Curr Hepatol Rep. 2025 Dec;24(1):10.1007/s11901-025-00713-7

  31. Vieira Barbosa J, et al. Fibrosis‐4 index as an independent predictor of mortality and liver‐related outcomes in NAFLD. Hepatology Communications. 2021;6:765-779.

  32. Tsochatzis EA. Screening for liver fibrosis - sequential non-invasive testing works best. J Hepatol. 2023;79:263-265.

  33. Younossi ZM, et al. Global consensus recommendations for metabolic dysfunction-associated steatotic liver disease and steatohepatitis. Gastroenterology. 2025;169:1017-1032.e2.

  34. Harrison SA, et al. Challenges and opportunities in NASH drug development. Nat Med. 2023;29:562-573.

  35. Noureddin M, et al. Expert Panel Recommendations: Practical Clinical Applications for Initiating and Monitoring Resmetirom in Patients With MASH/NASH and Moderate to Noncirrhotic Advanced Fibrosis. Clin Gastroenterol Hepatol. 2024;22:2367-2377.

  36. British Society of Gastroenterology (BSG) ELF test (Enhanced Liver Fibrosis). Available at: https://www.bsg.org.uk/clinical-resource/elf-test-(enhanced-liver-fibrosis). Last accessed: May 2026.

  37. Patel K, Sebastiani G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Rep. 2020;2:100067.

  38. Banini BA, Sanyal AJ. Nonalcoholic fatty liver disease: epidemiology, pathogenesis, natural history, diagnosis, and current treatment options. Clin Med Insights Ther. 2016;8:75-84.

  39. Bozic D, et al. Ultrasound methods for the assessment of liver steatosis: A critical appraisal. Diagnostics (Basel). 2022;12.

  40. Stal P. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance. World J Gastroenterol. 2015;21:11077-11087.

  41. Honda Y, et al. Elastography techniques for the assessment of liver fibrosis in non-alcoholic fatty liver disease. Int J Mol Sci. 2020;21:4039.

  42. Allen AM, et al. Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design. J Hepatol. 2022;77:1237-1245.

  43. D'Amico G, et al. Towards a new definition of decompensated cirrhosis. J Hepatol. 2022;76:202-207.

  44. Canbay A, et al. Healthcare resource utilization and costs among nonalcoholic fatty liver disease patients in Germany. Ann Transl Med. 2021;9:615.

  45. Wang S, Friedman SL. Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). Sci Transl Med. 2023;15:eadi0759.

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