A healthy liver contains some fat, but excessive fat buildup can compromise liver function.
Fatty liver disease or hepatic steatosis is a disease caused due to the accumulation of extra fat in the liver. Alcoholic (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two types of fatty liver disease. NAFLD is the most common form of chronic type of liver disease globally and the most common liver disease among children.
Importance of the Liver
The liver performs critical functions as follows:
- Metabolism: The liver metabolizes carbohydrates, fats, and proteins
- Detoxification: The liver removes waste materials, including alcohol, drugs, metabolic waste products, and toxins from the body. In addition, the liver transforms toxic ammonia (released from protein breakdown) into urea, which can be safely eliminated from the kidneys.
- Production of bile, blood proteins (such as albumin), and clotting factors. Bile fluid helps in breaking down fats in the small intestine, thereby aiding in fat digestion and absorption.
- Storage of glycogen (provides energy), vitamins (vitamins A, B12, and D), and minerals (such as copper and iron). In the liver, glucose is stored as glycogen and released whenever required.
- Regulation of blood sugars, blood volume, blood pressure, and cholesterol. The liver breaks down fat to produce triglycerides and cholesterol.
- Immune function: The liver contributes to the body’s immunity against harmful, disease-causing pathogens. Kupffer cells of the liver remove foreign particles and bacteria from the bloodstream.
- Hormones: Thyroid and sex hormones are regulated by the liver.
- Glucose formation (gluconeogenesis): When blood sugar levels are low in the body, the liver produces glucose from non-carbohydrate sources such as glycerol and amino acids via gluconeogenesis.
Similarities Between AFLD and NAFLD
- Both types of fatty liver disease are caused due to excess fat accumulation in the liver.
- These types are serious health problems globally.
- Both diseases have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma.
- Both diseases are frequently accompanied by extrahepatic complications affecting organs other than the liver.
- Fatty liver disease is usually asymptomatic.
- In the case of symptomatic disease, non-specific symptoms such as fatigue and malaise may be experienced. Other signs and symptoms include liver enlargement (hepatomegaly), pain in the upper right quadrant of the abdomen, loss of appetite, confusion, muscle weakness, and jaundice (yellowness of eyes and skin).
- In the case of cirrhosis or severe disease, one may experience esophageal varices, pedal edema, ascites, easy bruising, and petechiae.
- Fatty liver disease is diagnosed based on liver function tests (LFTs), imaging studies [ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI)] to examine fatty infiltrates, and biopsy to study microscopic features.
Differences between AFLD and NAFLD
- Cause/Etiology:
The key difference between alcoholic and non-alcoholic fatty liver is that alcoholic fatty liver is caused due to alcohol consumption whereas non-alcoholic fatty liver is primarily caused due to obesity and insulin resistance. Diabetes, pre-diabetes, being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure (hypertension) are the major reasons for non-alcoholic fatty liver.
The liver metabolizes alcohol, and alcohol prevents fatty acid oxidation. Chronic alcohol abuse can therefore accumulate fat (triglycerides) in liver cells and give rise to AFLD.
In NAFLD, insulin inhibits the breakdown of fat molecules (lipolysis) and promotes triglyceride (TAG) and DAG (Diacyl Glycerol) storage in hepatocytes, causing fatty liver. DAG and its metabolites are toxic to hepatocytes. NAFLD is also associated with changes in the gut microbiome and disrupted circadian rhythms.
High fat-high carbohydrate intake leads to the accumulation of excess fat in the liver, de novo lipogenesis, and insulin resistance. In non-alcoholic steatohepatitis (NASH), mitochondria or energy powerhouses of cells get dysfunctional resulting in increased oxidative stress, activation of immune cells known as macrophages, production of inflammatory substances, and apoptosis of liver cells. In the fibrotic/cirrhotic stage, excess production of extracellular matrix is observed, resulting in scarring of liver tissues.
NAFLD causes include medications (amiodarone, glucocorticoids, methotrexate, and tamoxifen); metabolic abnormalities (galactosemia, lipodystrophy, homocystinuria, tyrosinemia, and glycogen storage diseases); nutritional status (obesity, severe malnutrition, starvation diet, and total parenteral nutrition); and others [celiac sprue, Wilson disease, and inflammatory bowel disease (IBD)].
- History:
AFLD patients present with a history of chronic and heavy alcohol consumption, which means consuming more than moderate amounts of alcohol regularly over an extended period.
You may develop NAFLD without consuming excessive amounts of alcohol. Contributing factors include sedentary lifestyles, poor dietary habits, and metabolic risk factors such as diabetes, hypertension, and obesity.
- Stages/Disease Progression:
There are several stages of AFLD as alcohol-related liver disease, alcoholic hepatitis, fibrosis, cirrhosis, and even hepatic (liver) failure if alcohol consumption is not discontinued.
NAFLD may progress from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. In the cirrhosis stage, the liver gets damaged permanently, and it can lead to liver cancer (hepatocellular carcinoma).
In other words, deposits of fat cause liver enlargement (fatty liver), further scar tissue forms, and more liver cell injury occurs (liver fibrosis). NASH is characterized by fat cells. With inflammation and scarring. Finally, scar tissue replaces liver cells, making the liver hard and unable to work properly (cirrhosis).
- Clinical features:
AFLD presents with varying severity whereas NAFLD is usually mild. Disease progression is usually slower in NAFLD and is affected by metabolic factors instead of alcohol intake.
In AFLD, the aspartate transaminase (AST)/alanine transaminase (ALT) ratio exceeds 2.0, whereas in NAFLD, the AST/ALT ratio is usually below 1.0.
In cirrhosis without alcoholic hepatitis (liver inflammation), normal to slightly elevated liver enzymes are observed with low albumin, normal-to-high international normalized ratio (INR) values, low platelet count, and elevated bilirubin level.
In cirrhosis with alcoholic hepatitis, elevated bilirubin (more than 3 to 5 mg%), increased AST/ALT ratio (but below 2), and high INR with low hemoglobin, albumin, and platelet counts are observed. In addition, in AFLD, hepatic glutathione S-transferase (GST) levels are significantly high.
- Microscopic features and pathogenesis
- Fatty degeneration of liver cells: In AFLD, fatty degeneration of liver cells occurs to a lesser degree, whereas in NAFLD, it is observed to a greater extent.
- Inflammatory cell infiltration: In alcoholic fatty liver, inflammatory cell infiltration is observed more pronounced than NAFLD.
- Venous fibrosis, phlebosclerosis, canalicular cholestasis, foamy degeneration, bridging necrosis, fibrosis, cirrhosis, and lymphocytic phleboliths: These features were more common in AFLD compared to NAFLD.
- Iron/Hemosiderin pigmentation: The presence of hemosiderin is more frequent in AFLD than in NAFLD.
- Genetics:
Genes involved in ALD include Patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH).
NASH-related genes include ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and insulin receptor substrate-1 (IRS1), in addition to TM6SF2 and PNPLA3.
- Treatment
AFLD patients are advised to quit alcohol consumption since alcohol can reverse liver damage in the pre-cirrhotic stage) and are also provided nutritional support. In advanced cases, medical interventions are provided.
Treatment recommendations for NAFLD include lifestyle modifications such as weight management and regular physical exercise (if obese), adherence to a balanced diet, limiting alcohol intake, and avoiding unnecessary medications. NAFLD patients are provided Vitamin E supplements and are advised to improve their blood sugar levels (if diabetic). In both types, liver transplants are carried out in the severe (cirrhosis) stage.
Final thoughts
The liver is a multitasking organ that performs several important functions, including digestive, metabolic, detoxification, and immunological processes. Thus, liver health is vital for overall well-being, and liver disease can have significant health implications.
Whether you consume alcohol or not, you may develop fatty liver. The key difference between AFLD and NAFLD lies in their underlying cause, with AFLD being linked to excessive alcohol intake and NAFLD being related to metabolic factors such as type 2 diabetes and obesity.
Both conditions can progress to more severe liver diseases, therefore, early detection and prompt treatment are of utmost importance. Addressing underlying risk factors and lifestyle modifications are crucial to preventing and managing fatty liver disease.
