Steatotic liver disease
Mads Israelsen, Sven Francque, Emmanuel A Tsochatzis, Aleksander Krag Steatotic liver disease is
the overarching term for conditions characterised by abnormal lipid accumulation in the liver (liver
or hepatic steatosis). Steatotic liver disease encompasses what was previously termed non-alcoholic
fatty liver disease (NAFLD), which is now called metabolic dysfunction-associated steatotic liver
disease (MASLD). Additionally, steatotic liver disease includes alcohol-related liver disease (ALD) and
MetALD, the new classification for the overlap between MASLD and ALD, and rare causes of liver
steatosis. Cirrhosis is globally the 11th leading cause of death, and steatotic liver disease has become
the leading cause of cirrhosis in the EU and USA. Steatotic liver disease affects around 30% of the
global population and is mainly driven by obesity, type 2 diabetes, and alcohol intake, but only a
minor proportion with steatotic liver disease progress to cirrhosis. The presence and progression of
liver fibrosis led by hepatic inflammation is the main predictor of liver-related death across the
entire spectrum of steatotic liver diseases. A combination of recent advancements of widely
available biomarkers for early detection of liver fibrosis together with considerable advancements in
therapeutic interventions offer the possibility to reduce morbidity and mortality in patients with
steatotic liver disease. This Seminar covers the recent reclassification of steatotic liver disease and
how it reflects clinical practice and prognosis. For early detection of liver fibrosis, we propose a
collaborative diagnostic framework between primary care and liver specialists. Lastly, we discuss
current best practices for managing steatotic liver disease, we explore therapeutic targets across the
spectrum of steatotic liver diseases, and we review the pipeline of drugs in development for MASLD.
Introduction In this Seminar we address the recent reclassification and new nomenclature of fatty
liver disease as steatotic liver disease, encompassing what was formerly known as non-alcoholic
fatty liver disease (NAFLD)—and its subtype non-alcoholic steatohepatitis (NASH)—and alcohol-
related liver disease (ALD), and other rare causes of liver steatosis.1 This reclassification and new
nomenclature, initiated by several regional liver societies, has resulted from a large multi-
stakeholder consensus-driven process following a strict methodology and now has global
endorsement from more than 75 societies.2 Importantly, this shift integrates steatotic liver disease
within a spectrum encompassing ALD and recognises the potential coexistence of factors that
synergistically drive disease progression. Given that more than 30% of the global population has liver
steatosis,3,4 and that in most countries a large proportion of these populations concurrently
consume alcohol (with 5–15% engaging in harmful alcohol consumption),5,6 these figures underline
the far reaching implications of this reclassification for clinical practice. The new framework,
acknowledging both cardiometabolic risk factors (CMRFs) and alcohol consumption, is of crucial
importance for various medical fields, including primary care, internal medicine, hepatology,
gastroenterology, endocrinology, and obesity medicine. Reclassification also holds substantial
importance for public health and health-care systems.7 Furthermore, the steatotic liver disease
framework facilitates the conceptualisation of steatotic liver disease subclasses as a dynamic and
overlapping spectrum allowing for the integration of diagnostic and management recommendations
across these subclasses. This Seminar builds on this new approach and integrates the evidence
across steatotic liver disease subclasses. While liver steatosis is a common feature in many liver
diseases, most cases are associated with alcohol consumption and CMRFs, particularly type 2
diabetes and overweight, or a combination of these.1 The group of less common causes of liver
steatosis are distinct and are not the focus of this Seminar. The naming of this condition as steatotic
liver disease underscores liver steatosis as a central feature. However, it is well recognised that liver
inflammation and fibrosis are the key clinical targets due to their association with disease severity
and prognosis (panel 1).11–13 Epidemiology of steatotic liver disease The predominant risk factors
for steatotic liver disease include obesity, insulin resistance, and alcohol consumption. WHO
estimates that in 2022, 43% of all individuals 18 years and older were overweight (BMI >25 kg/m²)
and 16% were living with obesity (BMI >30 kg/m²). In 2021, there were 529 million (95% uncertainty
interval [UI] 500–564) people living
