MASH

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In recognition of the metabolic basis of the following liver diseases, NASH (non-alcoholic steatohepatitis) is now called MASH (metabolic dysfunction–associated steatohepatitis), while NAFLD (non-alcoholic fatty liver disease) is now called MASLD (metabolic dysfunction-associated steatotic liver disease).¹

MASLD is defined by the presence of hepatic steatosis and >1 cardiometabolic risk factor.¹ MASH is a progressive form of MASLD defined by three hallmarks; steatosis, ballooning and inflammation, with or without fibrosis.^2,3

MASLD is the most common chronic liver disease in the world.^4,5 MASH is already the leading cause of liver transplantation among U.S. women and patients over the age of 65, while MASLD is likely to become the leading global cause of liver transplantation by 2030.^6,7

MASH is largely a “silent” disease, with nearly 90% of people with MASH remaining undiagnosed.⁸

Many undiagnosed patients have early-stage disease.⁸ If left untreated, this can progress to advanced fibrosis and incur significant healthcare utilisation, economic and wellbeing costs.⁸

Evidence from a systematic review and meta-analysis of five MASLD cohort studies showed that MASLD and MASH are associated with an increase in liver-related and all-cause mortality.⁹

In addition, there is growing evidence of several extrahepatic complications, including metabolic syndrome and type 2 diabetes as well as cardiovascular disease, chronic kidney disease and malignancy.^4,5,9,10

The risk of all-cause mortality increases with fibrosis stage from F2 onwards^*9

The risk of liver-related mortality increases exponentially as fibrosis stage increases⁹

MASLD patients have a high risk of death from cardiovascular disease⁵

* Compared with F0.

^*Based on a cohort study of 229 patients with biopsy-proven MASLD showing that patients with advanced fibrosis (fibrosis stage 3-4) and an MASLD activity score (MAS)^† 0-8 had a 4-fold increased risk of CVD mortality compared to patients without MASH or fibrosis. Source: National Registry of Population in Sweden.⁴
^†MAS refers to NAS (NAFLD activity score).⁴

Both the presence of these comorbidities and their bidirectional relationship, add to the risks of MASH.¹²

more than 1 in 3 people living with obesity

more than 1 in 3 people living with type 2 diabetes

Although MASH is thought to be a relatively indolent and slow-progressing disease,¹⁶ 1 in 3 patients with MASH are estimated to develop progressive fibrosis.^17*

^*Fibrosis progression was estimated following a systematic review up to June 2013 and subsequent meta-analysis of seven studies in patients with MASH (N=116) who underwent paired liver biopsies at least 1 year apart. Overall, 40 (34.5%) of patients with MASH developed progressive fibrosis.¹⁷

At all levels of care, early detection of at-risk MASH patients is critical.^17,18

International clinical practice guidelines recommend screening of patients at risk of MASH to help prevent progression and potentially life-threatening complications.^18,19

Primary care physicians can play a leading role in screening and stratifying patients using non-invasive tests (i.e., FIB-4, Fibroscan^® or ELF).¹⁸

EASL Clinical Practice Guidelines on non-invasive tests (NITs)¹⁸

Primary screening is an important first step

All patients with obesity, type 2 diabetes and/or metabolic risk factors should undergo primary risk assessment with FIB-4 to rule out advanced fibrosis.^18,20

The most important role at this point is to prevent the development of MASH fibrosis in patients with simple steatosis. This can be achieved by reinforcing the importance of lifestyle measures (outlined in the dropdown below).²⁰

Optimal long-term management of MASH encompasses holistic care along the cardiometabolic spectrum.¹⁸

Early diagnosis can mean that lifestyle modifications such as changes in diet and exercise can pause or possibly even reverse the progression of MASH in its early stages.²¹

Weight loss can induce histological improvements in patients with MASH.²²

The amount of weight loss can determine MASLD outcomes,²² with some guidelines recommending a weight loss target of 10% or more to achieve the highest rates of histological improvements.²³

Rinella ME, Lazarus JV, Ratziu, et al. J Hepatol. 2023;79(6):1542–1556.

Pais R, Barritt AS 4th, Calmus Y, et al. J Hepatol. 2016;65(6):1245–1257.

Younossi ZM, Koenig AB, Abdelatif D, et al. Hepatology. 2016;64:73–84.

Ekstedt M, Hagström H, Nasr P, et al. Hepatology. 2015;61(5):1547–1554.

Männistö VT, Salomaa V, Färkkilä M, et al. Liver Int. 2021;41(11):2590–2600–

Gill MG, Majumdar A. World J Hepatol. 2020;12(12):1168–1181.

Paklar N, Mijic M, Filipec-Kanizaj T. Biomedicines 2023;11(11):3096.

Schattenberg JM, Lazarus JV, Newsome PN, et al. Liver Int 2021;41(6):1227–1242.

Dulai PS, Singh S, Patel J, et al. Hepatology. 2017;65(5):1557–1565.

10.

Muthiah MD, Cheng Han N, Sanyal AJ. Diabetes Obes Metab 2022;24(Suppl. 2):3–14.

11.

Konyn P, Ahmed A, Kim D. Clin Mol Hepatol 202329(Suppl):S43–S57.

12.

Glass LM, Hunt CM, Fuchs M, et al. Fed Pract 2019;36(2):64–71.

13.

Machado M, Marques-Vidal P, Cortez-Pinto. J Hepatol 2006;45(5):600–606.

14.

Younossi ZM. J Hepatol 2019;70(3):531–544.

15.

Gastaldelli A, Cusi K. JHEP Rep. 2019;1(4):312-328.

16.

Loomba R, Adams LA. Hepatology 2019;70(6):1885–1888.

17.

Singh S, Allen AM, Wang Z, et al. Clin Gastroenterol Hepatol 2015;13:643–654.

18.

Clark JM, Cryer DRH, Morton M, Shubrook JH. Diabetes Obes Metab 2023;25(6):1421–1433.

19.

EASL-EASD-EASO. J Hepatol. 2016;64(6):1388–402.

20.

Kuchay MS, Misra A. Diabetes Metab Syndr. 2022;16(3):102446.

21.

Hallsworth K, Adams LA. JHEP Rep. 2019;1(6):468–479.

22.

Godoy-Matos AF, Silva Júnior WS, Valerio CM. Diabetol Metab Syndr. 2020;12:60.

23.

Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Gastroenterology. 2015;149(2):367–378.

24.

Francque S, Vonghia L. Adv Ther. 2019;36(5):1052-1074.

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HQ24SN00040, May 2024

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