MASH and Hepatic Fibrosis: Intersecting Metabolic Pathways

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Q&A

Q1. What is MASLD, and how does MASH fit within this disease spectrum?

MASLD (metabolic dysfunction–associated steatotic liver disease) refers to hepatic fat accumulation in the presence of cardiometabolic risk factors such as diabetes, hypertension, dyslipidaemia, or central obesity. MASH represents the more severe and progressive end of this spectrum, characterised by hepatic inflammation and fibrosis. The updated MASLD framework simplifies diagnosis by requiring the presence of steatosis plus at least one cardiometabolic risk factor, reflecting real-world clinical practice. [1]

Q2. How common is MASLD/MASH, and which populations are most affected?

MASLD affects around 65% of adults globally, with increasing prevalence due to rising rates of obesity, diabetes, and sedentary behaviour. [7] 

Both urban and rural populations are affected, and disease onset is occurring at younger ages. Importantly, MASLD is also seen in lean individuals, highlighting that normal body weight does not exclude risk. [8,9,10] 

Q3. Why is MASLD/MASH particularly relevant to cardiology practice?

MASLD/MASH is strongly associated with cardiovascular disease. Patients have a 1.5x increased risk of heart failure, atrial fibrillation, and cardiovascular mortality. Across disease stages, cardiovascular events remain the most common cause of death, exceeding liver-related outcomes such as cirrhosis or hepatocellular carcinoma.[2,3]

Q4. Why is fibrosis considered the key prognostic marker in MASLD/MASH?

The fibrosis stage is the strongest predictor of both liver-related and non-liver-related outcomes. As fibrosis advances, the risk of cardiovascular events and all-cause mortality increases substantially. Steatosis and inflammation alone are less predictive of long-term risk, underscoring the importance of fibrosis assessment in disease management.[11,12] 

Q5. What challenges exist in current approaches to diagnosing liver fibrosis?

Routine liver enzymes lack sensitivity, and ultrasound detects steatosis only when fat accumulation is advanced. Liver biopsy, while diagnostic, is invasive and impractical for large-scale screening. FibroScan and other imaging tools face logistical and access barriers, limiting their routine use in many settings.[5] 

Q6. How can non-invasive tests be used to identify patients with advanced fibrosis?

Simple blood-based scores such as FIB-4 and APRI are useful first-line tools due to their high sensitivity. However, many patients fall into indeterminate risk categories. Newer algorithms, such as ADAPT, which combine Pro-C3 with age, diabetes status, and platelet count, improve specificity and help identify patients with advanced fibrosis while reducing unnecessary referrals and imaging.[6] 

Q7. What is the rationale for a stepwise screening strategy in MASLD/MASH?

A stepwise approach enables broad, low-cost screening with sensitive tools, followed by more specific tests in patients at higher risk or with indeterminate results. This strategy allows for early identification of clinically meaningful fibrosis while minimising over-investigation and healthcare burden. [12,13]

Q8. What are the core management principles for patients with MASLD/MASH?

Lifestyle modification remains foundational. A 5–10% weight loss is associated with improvements in steatosis, inflammation, and early fibrosis. Pharmacological options are emerging, including agents targeting metabolic dysfunction and fibrosis, alongside established therapies such as statins and diabetes treatments. Management should be individualised and multidisciplinary. [14,15,16,17]