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Figure 1. Factors contributing to the development of liver steatosis. MASLD: Metabolic dysfunction-associated steatotic liver disease;
NAFLD: nonalcoholic fatty liver disease; MAFLD: metabolic dysfunction-associated fatty liver disease; MetALD: metabolic dysfunction
and alcohol-related liver disease; ALD: alcoholic liver disease.

Nonetheless, several areas of uncertainty remain in our understanding of this condition. These span from a
more comprehensive understanding of its pathophysiology, to unlocking the key drivers of inflammation
and fibrosis, identifying accurate and available diagnostic tests, the cost-effectiveness of screening strategies,
the molecular mechanisms linking NAFLD/MASLD to extrahepatic complications, and whether treatment
[39]
can reduce liver-related events .
Finally, in terms of natural history, cohort studies have shown that patients with NAFLD are at increased
risk of developing diabetes , chronic kidney disease [41,42] , extrahepatic cancers and cardiovascular disease
[40]
[43]
[44]
(CVD) , and heart failure [Figure 2] . Indeed, CVD (together with cancer) represents the most common
[45]
cause of death in these patients, while liver-related mortality becomes a significant concern once
inflammation and fibrosis are present [46,47] .
ALCOHOL CONSUMPTION AND PERCEIVED STIGMA
Following the advent of highly effective treatments for hepatitis C and widespread hepatitis B vaccination,
alcohol-related liver disease (ALD) and NAFLD became the most common disease entities leading to
[48]
cirrhosis and liver transplantation in developed countries . Indeed, alcohol use and obesity have been
identified as the major forces driving liver disease in the general population .
[49]
While in some instances, it is clear that one factor (metabolic dysfunction or alcohol) is the predominant
[50]
noxious stimulus leading to liver disease progression, these two conditions frequently overlap .
Furthermore, their negative impact on liver health is synergistic rather than additive and if combined with
genetic polymorphisms (i.e., variants in the PNPLA3 gene), they can increase the risk of liver cirrhosis,
hepatocellular carcinoma, and death by more than eightfold . Alcohol consumption is highly prevalent
[51]
worldwide. According to the World Health Organization’s global status report on alcohol and health, 43%
of people worldwide consumed alcohol in 2018, with the average consumption per capita per year reaching
[52]
6.4 liters in 2016 . Spirits were the most commonly consumed alcoholic beverages, followed by beer and
wine. Moreover, 5.1% of the general population met the definition of alcohol use disorder according to the
Diagnostic and Statistical Manual of Mental Disorders. When interpreting these results, it is important to
note that the data are only as reliable as the original source data. For instance, consumer surveys assessing