Metabolic dysfunction-associated steatotic liver disease (MASLD): Secondary Care (Guidelines)

Following referral of patients likely to have MASLD/MetALD with possible significant fibrosis, the aims should be to ensure certainty of diagnosis, risk stratify, reinforce lifestyle advice and discharge or arrange follow-up as appropriate.

A liver stiffness of <10 kPa rules out compensated advanced chronic liver disease (cACLD), with levels >10kPa being suggestive of cACLD and values >15 kPA making cACLD probable.

These strata predict the risk of hepatic decompensation and hepatocellular carcinoma amongst patients with MASLD, with progression and regression on serial measurements correlating with increased and decreased risk.

Patients with LSM <10.0 can thus be safely discharged. Consider recommending a higher threshold of FIB-4 to trigger further referral.

Patients with LSM suggestive of cACLD (>10.0 and <15.0 kPa) have an increased medium-term risk, but relatively low absolute risk of event over the short term. This gives the opportunity to assess the response to lifestyle interventions over a 2-year period.

Those with a LSM >15 kPa are at increased risk of liver-related events and consideration should be given to follow up in cirrhosis clinics according to local protocols.

Taking into account patient wishes, co-morbidities and frailty, consider whether HCC surveillance is likely to be beneficial.

Those with a LSM >20 kPa or platelets <150 are at risk of clinically significant portal hypertension and should be considered for either endoscopic assessment for varices or empirical treatment with carvedilol.

See: V2 Metabolic dysfunction associated steatotic (MASLD): Primary Care (Guidelines)

Patients suitable for the MASLD pathway should be identified at the vetting. This allows for standardised nurse-led assessment, and, where appropriate, protocol-based discharge, follow-up or onward referral to consultant clinics.

• Update patient’s height, weight and calculate BMI
• Obtain past medical history, in particular noting any metabolic syndrome co-morbidities.
• Document performance status and baseline activity levels.
• Confirm alcohol history.
• Document drug history, including over the counter medication, herbal medications, recreational drugs.
• Complete liver screen, if not already done. See: Abnormal liver blood results referral pathway (Over 16’s).
• Screen for diabetes if not already done
• Update LFTs and FBC.
• Perform Fibroscan

• Discuss diagnosis of MASLD/Met-ALD and importance of lifestyle measures to prevent complications.
• Discuss the risk of liver cirrhosis, decompensated liver disease and liver cancer.
• Also discuss the increased risk of cardiovascular disease, non-hepatic malignancy and kidney disease associated with MASLD.
• Frame lifestyle changes as long-term changes to maintain/preserve health and well-being rather than quick fixes.
• Reinforce guidance regarding weight loss, alcohol, and exercise.
• Refer to local weight loss programs, where applicable. See Healthy weight (Guidelines)

Patients with LSM <10.0 who meet the following criteria:

• Typical LFTs
• Overweight / obese with at least one metabolic syndrome complication
• Negative liver screen, or minor abnormalities (see above)

Also discharge patients with LSM <10.0 not meeting the above criteria, deemed appropriate for discharge by liver MDT/Consultant discussion.

On discharge

• Recommend repeating FIB-4 in 3 years’ time, unless inappropriate on grounds of age (eg will be ≥ 75 years at that time), frailty or co-morbidity (discuss at Liver MDT/Consultant if required).
• Set a raised threshold for FIB-4 for the GP to consider referral.

FIB-4 threshold for re-referral

Refer to consultant clinic or discuss at MDT:

LSM > 10.0 (request ultrasound to exclude focal liver lesion and look for features of cirrhosis if not previously performed).

Consultant Clinic or MDT discussion:

Review results and decide on likelihood of established cirrhosis.

• For patients without definite cirrhosis, particularly those with a LSM of 10 to 15 kPa, consider the appropriateness of an interval Fibroscan (eg 2 years) after lifestyle interventions, or liver biopsy to further define risk.
• Interval Fibroscan may be via the nurse-led pathway with instruction to discharge if LSM <10.0 kPa.
  If doing so, also set instructions for whether further FIB-4 monitoring is appropriate and, if so, what threshold should be applied for further referral.
• For patients with established cirrhosis manage according to standard practice.
• As new drug therapies become available, consider the appropriateness of these.

1. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023 Dec;79(6):1542–56.
2. The Scottish Health Survey 2022 – volume 1: main report. [cited 2024 Apr 4]; Available from: https://www.gov.scot/publications/scottish-health-survey-2022-volume-1-main-report/
3. Roskilly A, Hicks A, Taylor EJ, Jones R, Parker R, Rowe IA. Fibrosis progression rate in a systematic review of placebo-treated nonalcoholic steatohepatitis. Liver Int. 2021 May;41(5):982–95.
4. Macpherson I. Ultrasound findings amongst patients enrolled in NHS Tayside iLFTs pilot. Personal communication. 2024 May 30;
5. McPherson S, Hardy T, Dufour J-F, Petta S, Romero-Gomez M, Allison M, et al. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis. Am J Gastroenterol. 2017 May;112(5):740–51.
6. Anstee QM, Berentzen TL, Nitze LM, Jara M, Jensen AB, Kjær MS, et al. Prognostic utility of Fibrosis-4 Index for risk of subsequent liver and cardiovascular events, and all-cause mortality in individuals with obesity and/or type 2 diabetes: a longitudinal cohort study. Lancet Reg Health Eur. 2024 Jan;36:100780.
7. Shang Y, Akbari C, Dodd M, Zhang X, Wang T, Jemielita T, et al. Association between longitudinal biomarkers and major adverse liver outcomes in patients with non-cirrhotic metabolic dysfunction-associated steatotic liver disease. Hepatology. 2024 Aug 7;10.1097/HEP.0000000000001045.
8. Hagström H, Talbäck M, Andreasson A, Walldius G, Hammar N. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease. J Hepatol. 2020 Nov;73(5):1023–9.
9. Kjaergaard M, Lindvig KP, Thorhauge KH, Andersen P, Hansen JK, Kastrup N, et al. Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease. J Hepatol. 2023 Aug;79(2):277–86.
10. Pearson M, Nobes J, Macpherson I, Gold L, Miller M, Dow E, et al. Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality. JHEP Rep. 2024 Jun 1;6(6):101062.
11. Mottin CC, Moretto M, Padoin AV, Swarowsky AM, Toneto MG, Glock L, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg. 2004 May;14(5):635–7.
12. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002 Sep;123(3):745–50.
13. Cacciottolo TM, Kumar A, Godfrey EM, Davies SE, Allison M. Spleen Size Does Not Correlate With Histological Stage of Liver Disease in People With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2023 Feb;21(2):535-537.e1.
14. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015 Aug;149(2):367-78.e5; quiz e14-5.
15. Linde JA, Jeffery RW, French SA, Pronk NP, Boyle RG. Self-weighing in weight gain prevention and weight loss trials. Ann Behav Med. 2005 Dec;30(3):210–6.
16. VanWormer JJ, Linde JA, Harnack LJ, Stovitz SD, Jeffery RW. Self-weighing frequency is associated with weight gain prevention over 2 years among working adults. Int J Behav Med. 2012 Sep;19(3):351–8.
17. Tate DF, Lutes LD, Bryant M, Truesdale KP, Hatley KE, Griffiths Z, et al. Efficacy of a Commercial Weight Management Program Compared With a Do-It-Yourself Approach: A Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2226561.
18. Marti-Aguado D, Calleja JL, Vilar-Gomez E, Iruzubieta P, Rodríguez-Duque JC, Del Barrio M, et al. Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease. J Hepatol [Internet]. 2024 Jul 4; Available from: http://dx.doi.org/10.1016/j.jhep.2024.06.036
19. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959–74.
20. Shearer JE, Jones R, Parker R, Ferguson J, Rowe IA. The natural history of advanced chronic liver disease defined by transient elastography. Clin Gastroenterol Hepatol [Internet]. 2022 Mar 22 [cited 2022 Mar 30];0(0). Available from: https://www.cghjournal.org/article/S1542-3565(22)00290-7/pdf
21. Mózes FE, Lee JA, Vali Y, Alzoubi O, Staufer K, Trauner M, et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023 Aug;8(8):704–13.
22. Gawrieh S, Vilar-Gomez E, Wilson LA, Pike F, Kleiner DE, Neuschwander-Tetri BA, et al. Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD. J Hepatol [Internet]. 2024 May 16; Available from: http://dx.doi.org/10.1016/j.jhep.2024.05.008