MASLD: The Rebrand You've Never Heard Of

If a tree falls in the woods and no one is there, does it make a sound? 

This philosophical thought experiment could arguably be applied to NAFLD – non-alcoholic fatty liver disease. In 2023, experts from around the world renamed this condition MASLD: metabolic dysfunction-associated steatotic liver disease, with details published in Hepatology Journal. Outside the world of hepatology, nobody noticed.

Why the change? Several reasons. Firstly, ‘non-alcoholic’ failed to capture the underlying pathophysiology of the condition, and ‘fatty’ was considered stigmatizing. Second, it is more than just the name: the definition has also been altered, although 99% of people with NAFLD will meet the new MASLD criteria. Thirdly, how we approach the risks associated with metabolic liver dysfunction needs to change.

Hundreds of hours of work, thousands of airmiles, millions of keystrokes. But to date, it feels as if liver specialists have failed to engage its most important audience: general practice. The published update has the usual bias towards secondary care with a failure to acknowledge that primary care clinicians are the ones who are going to be identifying the condition, risk stratifying for progressive liver disease and advising on the majority of management in the majority of cases. 

As such, this condition remains small print in general practice, off the radar, a low priority. We need something to buy into, a rationale showing why this is important. In fact this already exists. 

Liver disease is on the rise in the UK. Government data shows a 64% increase in premature deaths related to liver disease in England over the past 20 years, with a near 4% rise from 2020 to 2021 alone. But much of this is down to increased alcohol consumption, so does MASLD matter? Yes, undoubtedly, but perhaps not for the reasons you and I would think. 

Until recently there has been uncertainty about the rates of progression of the metabolic-associated steatotic liver, however, the picture is becoming clearer. Around 20% of patients with MASL will progress to steatohepatitis, of which 20% progress to cirrhosis. With up to 38% of the global adult population affected by MASLD, that represents a significant future population with advanced liver disease. But the biggest problems with MASLD come from outside the liver, as a recent paper published in Gut Journal explains.

Take a guess at the single greatest cause of mortality in this group? Cardiovascular disease. A recent meta-analysis shows cardiac-specific mortality is over 4 times greater than liver-specific mortality. 

This may not surprise you given the clear links between MASLD, overweight/obesity and type 2 diabetes. What is more surprising is that after adjustment for factors such as weight and diabetes, the risk remains elevated. MASLD is an independent risk factor for CVD, with around a 35-50% increase in CVD mortality, increasing further in the presence of fibrosis or cirrhosis. 

The physiological effects of MASLD lead to systemic inflammation, driving both atherosclerosis and other cardiac complications, for example, the risk of heart failure increases by around a third compared to people without MASLD. These same effects also increase the risk of intra- and extra-hepatic cancers.

It may be that addressing this pro-inflammatory cycle explains why a recent Korean cohort study in JAMA demonstrated that SGLT2 inhibitor use in patients with T2DM and MASLD was associated with MASLD regression and fewer adverse liver-related outcomes compared to sulphonylureas, DPP4i and pioglitazone.

While this data shows promise from the new breed of ‘anti-glycaemic’ medications it is only observational data and more work needs to be done to confirm the role of such drugs in MASLD management. The only validated treatment for MASLD to date is weight loss, where overweight/obesity is present. This has its own challenges which the medical community has so far failed to overcome, although GLP1 analogues and similar may change this landscape in the near future.

In the meantime, what can we do? Firstly, ensure we are identifying MASLD – follow up on that mildly raised ALT, and consider screening patients with T2DM and obesity. Secondly, offer advice and support on lifestyle measures such as weight loss and smoking cessation. Thirdly, look for and address modifiable risk factors for cardiovascular disease. 

Perhaps most importantly, let’s not forget the liver, silently working in the background, and think about it before it falls down.