Non-alcoholic fatty liver disease or NAFLD (also referred to as metabolic dysfunction-associated steatotic liver disease, or MASLD) is a chronic condition that develops due to an excessive accumulation of fat in the liver. It is usually seen in people who are overweight or obese. It is a heterogeneous disorder that encompasses a range of liver diseases with varying degrees of severity, clinical characteristics, and outcomes. NAFLD is the liver component of a cluster of conditions that are associated with metabolic dysfunction. NAFLD is defined by the presence of steatosis in more than 5% of hepatocytes in association with metabolic risk factors (particularly, obesity and type 2 diabetes) and in the absence of excessive alcohol consumption (=30 g per day for men and =20 g per day for women) or other chronic liver diseases.

The hallmark of NAFLD is hepatic steatosis, but the disease also encompasses non-alcoholic steatohepatitis (NASH) characterised by hepatic inflammation, hepatocyte damage, and fibrosis, highlighting the potentially progressive nature of the disease. The stage of hepatic fibrosis predicts both overall and liver-related mortality and is the strongest predictor of long-term clinical outcomes, with advanced fibrosis (stages 3 and 4) conveying the highest risk of mortality. In addition, metabolic dysfunctions such as insulin resistance, dyslipidemia, and cardiovascular disease are all associated with hepatic steatosis and seem to be more related to hepatic fat accumulation and NAFLD than obesity status.

Prevalence:
NAFLD has rapidly become the most common liver disease globally and is currently estimated to affect 38% of the global population. According to a recent systemic review and meta-analysis, the global prevalence of NAFLD increased from 25.3% in 1990-2006 to 38.0% in 2016-2019. As the most common chronic liver disease in developed countries, NAFLD affects 20–30% of the general population, 50–70% of diabetic patients, and 90% of morbidly obese individuals. The prevalence of adult NAFLD in India has been reported between 6.7% to 55.1% in 2021. The prevalence of paediatric NAFLD in India varies from 7.3% to 22.4% in the healthy population. It is found to be higher among those with diabetes (55.5% –59.7%), overweight or obesity (64.6% –95%) and metabolic syndrome (73%). The prevalence of prediabetes, diabetes, and metabolic syndrome among adults in India is 19–22%, 15–19%, and 30%, respectively, and is increasing in both urban and rural areas. 

Causes of NAFLD:

• Obesity can primarily cause NAFLD as excess adipose tissue increases free fatty acid (FFA) release to the liver.
• Insulin resistance leads to increased lipolysis, de novo lipogenesis (DNL), and fat accumulation.
• Type 2 Diabetes Mellitus (T2DM) as it impairs glucose metabolism and worsens liver fat buildup.
• High triglycerides & low HDL cholesterol promote hepatic lipid overload leading to Dyslipidemia
• High-Calorie Diets including excess sugar, refined carbs, and saturated fats promote lipogenesis.
• Hypothyroidism reduces metabolism, increasing fat accumulation in the liver.
• Polycystic Ovary Syndrome (PCOS) is associated with insulin resistance, increasing NAFLD risk.
• Gut Dysbiosis alters short-chain fatty acid production and increases gut-derived endotoxins that trigger liver inflammation.
• Sedentary lifestyle

Fatty liver is graded based on the amount of fat in the liver and the impact on liver health.

Grade	% of steatosis
Grade 0	No steatosis
Grade 1	< 33 %
Grade 2	33-66 %
Grade 3	> 66 %

Common Symptoms:

• Fatigue – Persistent tiredness or lack of energy
• Discomfort or Pain – A dull ache or discomfort in the upper right abdomen
• Unexplained Weight Loss – Some people may lose weight without trying
• Weakness – General feeling of being unwell or weak

Importance of Choline in NAFLD
Choline is a constituent of cell and mitochondrial membranes and of the neurotransmitter acetylcholine. It is a quaternary amine present in all mammalian tissues. It influences diverse processes such as lipid metabolism, signalling through lipid second messengers, methylation-dependent biosynthesis of molecules, activation of nuclear receptors, enterohepatic circulation of bile and cholesterol, plasma membrane fluidity and mitochondrial bioenergetics.

Choline is necessary to maintain normal liver function. It is involved in hepatic secretion of VLDL cholesterol, host–gut microbiota interactions and one-carbon metabolism, all of which underlie the pathogenesis of NAFLD. It is a precursor of phospholipids, phosphatidylcholine, lysophosphatidylcholine and sphingomyelin. Choline is an essential nutrient because its endogenous biosynthesis is generally not sufficient to meet human requirements.

"CD-36" is the primary protein responsible for the uptake of fatty acids from lipoproteins like VLDL, and to a lesser extent HDL, into cells. This process is facilitated by the interaction of CD-36 with the fatty acids within the lipoprotein, allowing the cell to absorb them for energy usage. The liver absorbs fatty acids (via CD36) and uses them to create cholesterol, phospholipids, and VLDL, which transport fats to other tissues. Cholesterol is also converted into bile acids for fat digestion. HDL brings cholesterol back to the liver, while LDL delivers it to tissues. The liver regulates lipid levels by recycling or excreting excess cholesterol.

• HL (Hepatic lipase) is a factor in hepatic intracellular lipid homeostasis.
• Lipids are taken up by the liver via several mechanisms.
• Lipoprotein receptors mediate in the endocytosis of whole lipoproteins
• HL modulate the binding of lipoproteins (e.g., chylomicron-remnants) to receptors, or stimulate the uptake of HDL-C (ester) directly, or facilitate selective uptake via SR-BI