Fatty liver disease

Fatty liver disease(FLD), also known ashepatic steatosisandsteatotic liver disease(SLD), is a condition where excessfatbuilds up in theliver.Often there are no or few symptoms.Occasionally there may be tiredness or pain in the upper right side of theabdomen.Complications may includecirrhosis,liver cancer, andesophageal varices.
The main subtypes of fatty liver disease aremetabolic dysfunction–associated steatotic liver disease(MASLD, formerly "non-alcoholic fatty liver disease" (NAFLD)) andalcohol-associated liver disease(ALD), with the category "metabolic and alcohol associated liver disease" (metALD) describing an overlap of the two.
The primary risks includealcohol,type 2 diabetes, andobesity.Other risk factors include certain medications such asglucocorticoids, andhepatitis C.It is unclear why some people with NAFLD develop simple fatty liver and others develop nonalcoholic steatohepatitis (NASH), which is associated with poorer outcomes.Diagnosis is based on themedical historysupported by blood tests,medical imaging, and occasionallyliver biopsy.
Treatment of NAFLD is generally by dietary changes and exercise to bring aboutweight loss.In those who are severely affected,liver transplantationmay be an option.More than 90% of heavy drinkers develop fatty liver while about 25% develop the more severealcoholic hepatitis.NAFLD affects about 30% of people in Western countries and 10% of people in Asia.NAFLD affects about 10% of children in the United States.It occurs more often in older people and males.
Fatty liver disease was classified into:
In 2023, a new nomenclature was chosen,with the classifications including:
Often there are no or few symptoms.Occasionally there may be tiredness or pain in the upper right side of the abdomen.
Fatty liver can develop into hepatic fibrosis, cirrhosis or liver cancer.For people affected by NAFLD, the 10-year survival rate was about 80%. The rate of progression of fibrosis is estimated to be one per 7 years in NASH and one per 14 years in NAFLD, with an increasing speed.There is a strong relationship between these pathologies and metabolic illnesses (diabetes type II, metabolic syndrome). These pathologies can also affect non-obese people, who are then at a higher risk.
Less than 10% of people with cirrhotic alcoholic FLD will develophepatocellular carcinoma,the most common type of primary liver cancer in adults, but up to 45% people with NASH without cirrhosis can develop hepatocellular carcinoma.
The condition is also associated with other diseases that influence fatmetabolism.
Fatty liver (FL) is commonly associated withmetabolic syndrome(diabetes,hypertension,obesity, anddyslipidemia), but can also be due to any one of many causes:
The fatty change represents theintracytoplasmaticaccumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around thenucleus(microvesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving a characteristicsignet ringappearance (macrovesicular fatty change). These vesicles are well-delineated and optically "empty" because fats dissolve during tissue processing. Large vacuoles may coalesce and produce fattycysts, which are irreversible lesions. Macrovesicularsteatosisis the most common form and is typically associated withalcohol, diabetes,obesity, andcorticosteroids. Acute fatty liver of pregnancy andReye's syndromeare examples of severe liver disease caused by microvesicular fatty change.The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight.
Defects infatty acid metabolismare responsible forpathogenesisof FLD, which may be due to imbalance in energy consumption and  its combustion,  resulting in lipid storage, or can be a consequence of peripheral resistance to insulin, whereby the transport of fatty acids fromadipose tissueto the liver is increased.Impairment or inhibition of receptor molecules (PPAR-α,PPAR-γandSREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute to fat accumulation. In addition, alcohol use disorder is known to damage mitochondria and other cellular structures, further impairing cellular energy mechanism. On the other hand, non-alcoholic FLD may begin as excess of unmetabolised energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying cause is reduced or removed.
Severe fatty liver is sometimes accompanied byinflammation, a situation referred to assteatohepatitis. Progression to alcoholic steatohepatitis (ASH) ornon-alcoholic steatohepatitis(NASH) depends on the persistence or severity of the inciting cause.Pathologicallesions in both conditions are similar. However, the extent of inflammatory response varies widely and does not always correlate with degree of fat accumulation. Steatosis (retention oflipid) and onset of steatohepatitis may represent successive stages in FLD progression.
Liver disease with extensive inflammation and a high degree of steatosis often progresses to more severe forms of the disease.Hepatocyteballooning andnecrosisof varying degrees are often present at this stage. Liver cell death and inflammatory responses lead to the activation ofhepatic stellate cells, which play a pivotal role in hepaticfibrosis. The extent of fibrosis varies widely.Perisinusoidalfibrosis is most common, especially in adults, and predominates inzone 3around the terminalhepatic veins.
The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors. In alcoholic FLD, the transition to cirrhosis related to continued alcohol consumption is well-documented, but the process involved in non-alcoholic FLD is less clear.
Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver enzymes are found in as many as 50% of patients with simple steatosis.The serumalanine transaminase(ALT) level usually is greater than theaspartate transaminase(AST) level in the nonalcoholic variant and the opposite in alcoholic FLD (AST:ALT more than 2:1). Simple blood tests may help to determine the magnitude of the disease by assessing the degree of liver fibrosis.For example, AST-to-platelets ratio index (APRI score) and several other scores, calculated from the results of blood tests, can detect the degree of liver fibrosis and predict the future formation of liver cancer.
Imaging studies are often obtained during the evaluation process.Ultrasonographyreveals a "bright" liver with increasedechogenicity. Pocket-sizedultrasounddevices might be used as point-of-care screening tools to diagnose liver steatosis.Medical imagingcan aid in diagnosis of fatty liver; fatty livers have lowerdensitythanspleensoncomputed tomography(CT), and fat appears bright inT1-weightedmagnetic resonance images(MRIs).Magnetic resonance elastography, a variant of magnetic resonance imaging, is investigated as a non-invasive method to diagnose fibrosis progression.Online calculators have been developed to assist in evaluating hepatic steatosis using CT and MRI findings.Histologicaldiagnosis byliver biopsyis the most accurate measure of fibrosis and liver fat progression as of 2018.Conventional imaging methods, such as ultrasound, CT and MRI, are not specific enough to detect fatty liver disease unless fat occupies at least 30% of the liver volume.
Decreasing caloric intake by at least 30% or by approximately 750–1,000 kcal/day results in improvement in hepatic steatosis.For people withNAFLDor NASH, weight loss via a combination of diet and exercise was shown to improve or resolve the disease.In more serious cases, medications that decrease insulin resistance,hyperlipidemia, and those that induce weight loss such as bariatric surgery as well as vitamin E have been shown to improve or resolve liver function.
Bariatric surgery, while not recommended in 2017 as a treatment for FLD alone, has been shown to revert FLD, NAFLD, NASH and advancedsteatohepatitisin over 90% of people who have undergone this surgery for the treatment ofobesity.
In the case of long-term total-parenteral-nutrition-induced fatty liver disease,cholinehas been shown to alleviate symptoms.This may be due to a deficiency in themethionine cycle.
NAFLD affects about 30% of people in Western countries and 10% of people in Asia.In the United States, rates are around 35% with about 7% having the severe form NASH.NAFLD affects about 10% of children in the United States.Recently the term Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace NAFLD.  MAFLD is a more inclusionary diagnostic name as it is based on the detection of fatty liver by histology (biopsy), medical imaging or blood biomarkers but should be accompanied by either overweight/obesity, type 2 diabetes mellitus, or metabolic dysregulation.The new definition no longer excludes alcohol consumption or coexistence of other liver diseases such as viral hepatitis. Using this more inclusive definition, the global prevalence of MAFLD is an astonishingly high 50.7%.Indeed, also using the old NAFLD definition, the disease is observed in up to 80% of obese people, 35% of whom progress to NASH,and in up to 20% of normal weight people,despite no evidence of excessive alcohol consumption. FLD is the most common cause of abnormalliver function testsin theUnited States.Fatty liver is more prevalent in Hispanic people than white, with black people having the lowest prevalence.
In the studyChildren of the 90s, 2.5% born in 1991 and 1992 were found by ultrasound at the age of 18 to have non-alcoholic fatty liver disease; five years latertransient elastographyfound over 20% to have the fatty deposits on the liver, indicating non-alcoholic fatty liver disease; half of those were classified as severe. The scans also found that 2.4% had a degree of liver fibrosis, which can lead to cirrhosis.
After thelockdown of the COVID-19 pandemic, a study demonstrated that 48% of patients with liver steatosis gained weight, while 16% had a worsened steatosis grade. Weight gain was associated with poor adherence to the suggested diet, reduced levels of physical activity, and increased prevalence of homozygosity for thePNPLA3rs738409 single nucleotide polymorphism.PNPLA3rs738409 is already a known risk factor for NAFLD.
A systematic review and meta-analysis, published in 2024, found thatgrowth hormonetherapy may help in the management of fatty liver disease.
Fatty liver disease can occur in pets such as reptiles (particularlyturtles) and birdsas well as mammals likecatsand dogs.The most common cause isovernutrition. A distinct sign in birds is a misshapen beak.  Fatty livers can be induced viagavagein geese or ducks to producefoie gras. Fatty liver can also be induced in ruminants such as sheep by a high-caloric diet.