1. New Nomenclature & Definitions
The terminology has shifted from “Non-alcoholic” to “Metabolic” to reduce stigma and better reflect the pathophysiology.
- MASLD (Metabolic dysfunction-associated Steatotic Liver Disease): Replaces NAFLD. Defined as hepatic steatosis with at least one cardiometabolic risk factor (Diabetes/Prediabetes, Obesity, Hypertension, Dyslipidemia) and without harmful alcohol intake.
- MASH (Metabolic dysfunction-associated Steatohepatitis): Replaces NASH. The progressive form characterized by inflammation and hepatocyte injury (ballooning).
- MetALD: A new category for individuals with MASLD who also consume increased alcohol (140–350 g/week for women, 210–420 g/week for men). This highlights the synergistic damage of metabolic disease and alcohol .
2. Epidemiology & Risk
- Prevalence:
- Type 2 Diabetes (T2D): ~70% have MASLD.
- Type 1 Diabetes (T1D): ~22% have MASLD.
- Primary Risk Driver: Liver Fibrosis (scarring) is the primary determinant of adverse outcomes (hepatic and non-hepatic).
- Mortality: The leading cause of death in people with MASLD is Cardiovascular Disease (CVD), followed by extrahepatic cancers and liver-related complications.
3. Screening & Diagnosis (The FIB-4 Index)
Because steatosis is so common in T2D, screening focuses on identifying advanced fibrosis (F3–F4) rather than just fatty liver.
- Who to Screen: All adults with Prediabetes or Type 2 Diabetes.
- Screening Tool: Fibrosis-4 Index (FIB-4).
- Inputs: Age, AST, ALT, Platelet Count.
- Interpretation & Action:
Low Risk (FIB-4 < 1.3): Unlikely to have advanced fibrosis. Manage in primary care; repeat screening in 1–3 years.
Indeterminate Risk (FIB-4 1.3 – 2.67): Requires “second-line” testing (e.g., transient elastography/FibroScan® or ELF test) to clarify risk.
High Risk (FIB-4 > 2.67): High probability of advanced fibrosis. Refer to Hepatology.
4. Management Strategies
A. Lifestyle Interventions (Cornerstone)
Weight Loss:
5%: Required to reduce liver fat.
7-10%: Required to resolve MASH (inflammation) and improve fibrosis.
Diet: The Mediterranean Diet is specifically recommended to reduce liver fat and improve outcomes.
Alcohol: Abstinence or minimization of alcohol intake is crucial.
B. Pharmacotherapy
Agents used for diabetes can have dual benefits for the liver.
Pioglitazone: Improves MASH resolution and improves fibrosis scores. (Watch for weight gain/heart failure).
GLP-1 Receptor Agonists (Semaglutide, Liraglutide): Improve MASH resolution but have not consistently shown improvement in fibrosis stage in trials as of time of guideline developement.
SGLT2 Inhibitors: Reduce liver fat content and liver enzymes; effects on histology (fibrosis) are less established but they provide cardiorenal protection.
Statins: Safe to use in MASLD. Do not discontinue statins due to mild liver enzyme elevations; they reduce cardiovascular risk, which is the leading cause of death in this population.
C. Surgical Management
Bariatric (Metabolic) Surgery: Can result in resolution of MASH and improvement in fibrosis in a high percentage of patients (up to 80-90%).
5. Diabetes Canada 2025 Clinical Practice Guidelines Recommendations
Key takeaways for the exam.
Screening: Screen all adults with T2D or prediabetes for MASLD with the FIB-4 Index (every 1-3 years) [Grade D, Consensus].
Pathway:
If FIB-4 < 1.3: Manage standard CV risks [Grade C, Level 3].
If FIB-4 > 2.67: Refer to specialist/hepatologist [Grade C, Level 3].
Lifestyle: Aim for 7-10% weight loss to improve liver fibrosis/inflammation [Grade B, Level 2].
Pharmacotherapy: Consider Pioglitazone or GLP-1 RAs (Semaglutide/Liraglutide) for patients with biopsy-proven MASH or those at high risk to improve liver health [Grade A/B].
Statins: Statins are safe and should be used to reduce CV risk in patients with MASLD [Grade B, Level 2].