MASH can have serious consequences.
Now is the time to act.

MASH: A “silent” disease?

MASLD is the most frequent liver disease in the world, affecting 1 in 4 adults and an estimated 7,800,000 Canadians.¹ MASH affects about 20% of patients with MASLD and is the second leading indication for liver transplantation in North America.¹

As the diagnosis of MASH involves liver biopsy, a costly and invasive procedure, MASH remains underdiagnosed despite its high prevalence.² As a “silent” disease, people with MASH feel well and are not symptomatic until the disease progresses to more advanced stages (i.e., cirrhosis).⁴

Left untreated, MASH poses a significant health, quality of life, and economic burden to both patients and their families, as well as on the healthcare system.⁷

The underlying threat of MASH

Studies have shown that MASLD and MASH are associated with an increase in liver-related and all-cause mortality.³

In addition, there is growing evidence that indicates that the effects of MASLD and MASH extend beyond the liver and are negatively associated with a range of chronic diseases, including cardiovascular disease, type 2 diabetes, chronic kidney disease, and cancer.¹

A large meta-analysis in patients with MASLD demonstrated

The risk of all-cause mortality increased with fibrosis stage from F2 onwards^8*†

Stage 2: HR = 1.46 (95% CI [1.08, 1.98]);
Stage 3: HR = 1.96 (95% CI [1.41, 2.72]);
Stage 4: HR = 3.66 (95% CI [ 2.65, 5.05]).
N = 17,301.

The risk of liver-related mortality increased exponentially as fibrosis stage increased^8†

Stage 2: HR = 4.07 (95% CI [1.44, 11.5]);
Stage 3: HR = 7.59 (95% CI [2.80, 20.5]);
Stage 4: HR = 15.1 (95% CI [5.27, 43.4]).
N = 17,301.*"

In patients with MASLD, the most common causes of death are cardiovascular disease and nonhepatic malignancy³

Disease progression can be rapid with MASH⁹

Increase in inflammation and ballooning associated with MASH can drive the development and progression of fibrosis.¹⁰ In approximately 1 in 5 patients, MASH can progress from no fibrosis (F0) to advanced fibrosis (F3) or cirrhosis (F4) in under six years.⁹

Normal

MASLD

MASH

Cirrhosis

Liver Failure

Steatosis

Hepatocyte ballooning

Lobular inflammation

Fibrosis

Mild

Moderate

Advanced

Cirrhosis

Normal

MASLD

10–30% of patients advance to next stage

MASH - Mild (F1) fibrosis

20–40% of patients advance to next stage

MASH - Significant (F2/F3) fibrosis

20–30% of patients advance to next stage

Cirrhosis (F4)

30–45% of patients advance to next stage

Liver Failure

Liver failure, hemorrhage

MASH is a multisystemic disease¹³

Can cause dysfunction in the following systems:

• 

  Cardiovascular

• 

  Vascular

• 

  Neurologic

• 

  Renal

• 

  Oncologic

• 

  Hepatic

• 

  Musculoskeletal

• 

  Pancreatic

More than 1 in 3 people living with overweight or obesity have MASH¹⁴

More than 1 in 3 people living with type 2 diabetes have MASH¹⁵

Similarly, patients are also at an increased risk of developing type 2 diabetes.³

Are you screening your at-risk patients for MASH?

Although MASH is thought to be a relatively indolent and slowly progressive disease, some patients can have an accelerated disease course.⁹ At all levels of care, early detection of at-risk MASH patients is critical.³ Clinical practice guidelines recommend screening patients at risk of MASH to help prevent progression and potentially life-threatening complications.³

Primary screening is an important first step

Primary care physicians can play a leading role in screening and stratifying patients using non-invasive tests (e.g., FIB-4, VCTE [FibroScan^®], or ELF).³

Selected key concepts to guide clinical practice:³

• 

  General population

  MASLD screening is not advised

• 

  High-risk patients

  Screen for advanced fibrosis (e.g., in T2DM, medically complicated obesity, family history of cirrhosis, or more than mild alcohol consumption)

• 

  Patients with hepatic steatosis or clinically suspected MASLD*

  Primary risk assessment with FIB-4

• 

  Patients with pre-DM, T2DM, or ≥ 2 metabolic risk factors (or imaging evidence of hepatic steatosis)

  Primary risk assessment with FIB-4 should be repeated every 1–2 years. When available, a secondary assessment of liver fibrosis severity may be considered.

* Based on the presence of obesity and metabolic risk factors.

FIB-4 calculator View AASLD Guidelines

FIB-4 can rule out advanced fibrosis in most patients³

AASLD Clinical Practice Guidelines recommend FIB-4 as a first-line assessment for general practitioners and endocrinologists based on its simplicity and minimal added cost.³

FIB-4 calculator

FIB-4 primary risk stratification

FIB-4 < 1.3* = LOW RISK

Patients can be followed in the primary care setting and periodically reassessed:

• Without prediabetes/T2DM and 1–2 metabolic risk factors: every 2–3 years
• With prediabetes/T2DM or ≥ 2 metabolic risk factors: every 1–2 years

FIB-4 ≥ 1.3 to ≤ 2.67 = INTERMEDIATE RISK

A secondary assessment should be done or the patient referred for further risk stratification^†

FIB-4 > 2.67 = HIGH RISK

Direct referral to gastroenterology / hepatology should be considered due to increased risk of clinically significant fibrosis

* In patients older than age 65, a FIB-4 cutoff of > 2.0 should be used. FIB-4 has low accuracy in those under age 35; thus, secondary assessment should be considered in those < 35 with increased metabolic risk or elevated liver chemistries.

† If being seen in a nongastroenterology / hepatology setting.

Management of MASH requires a multidisciplinary approach

Patients who are at intermediate or high risk for fibrosis should be referred to a liver specialist for further evaluation, management, and/or further diagnostic evaluation.³

Click below to view the AASLD Clinical Practice Guidelines on the clinical assessment and management of MASLD.

View AASLD Guidelines

A multidisciplinary approach to optimized care³

The majority of patients are in the primary care/endocrine setting, in which management of medical comorbidities should be optimized. Preference should be given to treatments for type 2 diabetes mellitus, hypertension, or obesity that likely also have beneficial effects on MASLD.³

Optimal care requires a multidisciplinary approach across the cardiometabolic spectrum.³

Close communication between gastroenterology / hepatology and primary care or endocrinology facilitates multidisciplinary management of metabolic comorbidities as well as the prioritization of medications or interventions that may also offer liver benefits. All patients should undergo dietary/nutritional assessment and a plan established for regular follow-up independent of gastroenterology / hepatology visits. The need for more specialized obesity management, including bariatric surgery referral, health psychology, and additional cardiology or lipid metabolic support, should be assessed on an individual basis.³

Early identification allows for intervention that may prevent future complications.³

Therapeutic approaches

The current therapeutic management of MASH relies on a three-tiered approach: lifestyle interventions, specific pharmacotherapy, and metabolic risk management. A program based on dietary change, weight loss, and structured exercise intervention are recommended by Canadian guidelines. Though clinical trials are ongoing, there are currently no pharmacological therapies licensed for the treatment of MASLD or MASH in Canada.¹

Multimodal treatment strategies for MASLD¹

A healthy diet and regular exercise form the foundation of treatment for the vast majority of patients with MASLD.³ Weight reduction should be recommended because, if sustained, it improves cardiovascular risk profile, steatosis, steatohepatitis (7–9% weight loss), and fibrosis (> 10% weight loss).¹

The time to act is NOW. Start screening your patients at risk of MASH.

FIB-4 calculator