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.
IF YOUR PATIENT HAS CARDIOMETABOLIC RISK FACTORS,
ACT NOW AGAINST THE UNDERLYING THREAT OF MASH
MASH is prevalent, chronic, progressive, and underdiagnosed.1,2
Millions of Canadians are at higher risk of morbidity and mortality from this silent disease.1,3,4
Early identification and intervention may prevent future complications.3
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What is MASH?
Although the terms NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) might be more familiar to you, their resiliance on exclusionary confounder terms and the use of potentially stigmatizing language were identified as principal limitations by leading experts and patient advocates.5 In 2023, the following nomenclature change was adopted:
- NAFLD is now called MASLD (metabolic dysfunction-associated steatotic liver disease)
- NASH is now called MASH (metabolic dysfunction-associated steatohepatitis)
MASLD is defined by the presence of hepatic steatosis and the finding of any cardiometabolic risk factor (if there are no other causes of hepatic steatosis).5 MASH is a progressive form of MASLD defined by the additional presence of macrovesicular hepatic steatosis, inflammation, and cellular injury (with or without fibrosis).3,5
Learn about the pathophysiology and hallmarks of MASH.
You can help drive change for your patients with MASH.
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 transpantation 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.6
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 ectend 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 onwards7*†
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 increased7†
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
* Compared with F0.
† Data based on a time-to-event meta-analysis; Medline and Embase databases were searched to include cohort studies reporting survival outcomes by fibrosis stage in biopsy-proven MASLD.
Survival estimates were pooled using reconstructed individual participant data.7
Pathogenesis and progression of MASH and associated liver fibrosis1
MASH can lead to progressive liver fibrosis, cirrhosis, and associated complications.
Adapted from Sebastiani G, et al. 2021.
Cardiovascular disease is the most common cause of death in patients with MASH8
Patients with MASH have a greater CVD risk vs. those with other liver diseases9
MASH is a multisystemic disease10
Vascular
Neurologic
Renal
Oncologic
Cardiovascular
Hepatic
Musculoskeletal
Pancreatic
More than
1 in 3
people living with overweight or obesity have MASH11
More than
1 in 3
people with type 2 diabetes have MASH12
Similarly, patients are also at an increased risk of developing type 2 diabetes.3
Early indentification and intervention may prevent future complications.3
Screening and diagnosis
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.13 The 20% rule of MASH progression: Approximately 20% of patients with MASH with advanced MASLD Fibrosis Score (F3) fibrosis or compensated cirrhosis will progress to cirrhosis or develop decompensation, respectively, over a 2-year time period.13
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 practice3
- General population-based screening for MASLD is not advised
- High-risk patients, such as those with T2DM, medically complicated obesity, family history of cirrhosis, or more than mild alcohol consumption, should be screened for advanced fibrosis
- All patients with hepatic steatosis or clinically suspected MASLD based on the presence of obesity and metabolic risk factors should undergo primary risk assessment with FIB-4
- In 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.
AASLD Clinical Practice Guidelines: Algorithm for the evaluation of patients at risk for or with established MASLD across practice settings3
Clinical Suspicion for Fatty Liver Disease
FIB-4 can rule out advanced fibrosis in most patients and should be used for periodic reassessment, as indicated.3
FIB-4 is recommended as a first-line assessment for general practitioners and endocrinologists based on its simplicity and minimal added cost.3
FIB-4 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.
† If being seen in a nongastroenterology/hepatology setting.
Management of MASH requires a multidisciplinary approach
View Guidelines 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
A healthy diet and regular exercise form the foundation of treatment for the vast cmajority of those with MASLD. Even modest amounts of weight loss can be impactful, with a 3–5% body weight reduction improving steatosis and > 10% improving MASH and fibrosis.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
A healthy diet and regular exercise form the foundation of treatment for the vast cmajority of those with MASLD. Even modest amounts of weight loss can be impactful, with a 3–5% body weight reduction improving steatosis and > 10% improving MASH and fibrosis.3
If your patients have cardiometabolic risk factors, the time to act is NOW. Start screening your patients at risk of MASH.
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References
- Sebastiani G, et al. Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1st International Workshop of the Canadian NASH Network (CanNASH). Canadian Liver Journal. 2022;5(1):61-90.
- Povsic M, et al. A Structured Literature Review of the Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH). Advances in Therapy. 2019;36(7):1574-1594.
- Rinella ME, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835.
- Cameron JL, et al. Current surgical therapy. 14th ed. Philadelphia, PA: Elsevier; 2023.
- Rinella ME, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542-1556.
- Romero-Gomez M. NAFLD and NASH: Biomarkers in Detection, Diagnosis and Monitoring. Switzerland: Springer International Publishing; 2020.
- Ng CH, et al. Mortality Outcomes by Fibrosis Stage in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2023;21(4):931-939.e935.
- 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. Frontiers in Cell and Developmental Biology. 2024;12.
- Sanyal AJ, et al. Cardiovascular disease in patients with metabolic dysfunction-associated steatohepatitis compared with metabolic dysfunction-associated steatotic liver disease and other liver diseases: A systematic review. Am Heart J Plus. 2024;41:100386.
- Muthiah MD, et al. A clinical overview of non-alcoholic fatty liver disease: A guide to diagnosis, the clinical features, and complications-What the non-specialist needs to know. Diabetes Obes Metab. 2022;24 Suppl 2:3-14.
- Quek J, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8(1):20-30.
- Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019;70(3):531-544
- Loomba R, et al. The 20% Rule of NASH Progression: The Natural History of Advanced Fibrosis and Cirrhosis Caused by NASH. Hepatology. 2019;70(6):1885-1888.
AASLD, American Association for the Study of Liver Diseases; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CKD, chronic kidney disease; cT1, corrected T1; CVD, cardiovascular disease; ELF, Enhanced Liver Fibrosis; FAST, FibroScan-AST; FIB-4, fibrosis-4 index; MAST, score derived from MRI-PDFF, MRE, and serum AST; MRE, magnetic resonance elastography; NIT, noninvasive test; PCP, primary care provider; PDFF, proton density fat fraction; T2DM, type 2 diabetes mellitus; VCTE, vibration-controlled elastography.
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