Fatty liver

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Fatty liver is a type of liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver (“steato”, meaning fat, “hepatitis“, meaning inflammation of the liver). Classically seen in alcoholics, steatohepatitis also is frequently found in people with diabetes and obesity. When not associated with excessive alcohol intake, it’s referred to as non-alcoholic steatohepatitis, or NASH. Steatohepatitis of either etiology may progress to cirrhosis, and NASH is now believed to be a frequent cause of unexplained cirrhosis.

Physicians do not well manage fatty liver^[1].

Fatty liver is the fatty degeneration of the parenchymal cells causing a yellow discoloration of the liver. It is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis. Despite having multiple causes, fatty liver disease (FLD) can be considered a single disease that occurs worldwide in those with excessive alcohol intake and those who are obese (with or without effects of insulin resistance). The condition is also associated with other diseases that influence fat metabolism.^[2] Morphologically it is difficult to distinguish alcoholic FLD from non alcoholic FLD and both show micro-vesicular and macrovesicular fatty changes at different stages.

Fatty liver disease is prevalent among 10%- 24% of general population in various countries.^[3] However among obese individuals the condition is observed in up to 75% of people, 35% of whom, despite no evidence of excessive alcohol consumption, will lead to non alcoholic FLD.^[4] It is the most common cause of abnormal liver function test in the US.^[3] African Americans and Mexican Americans have higher frequencies of unexplained serum aminotransferase elevations than those reported in whites but prevalence of FLD among different racial groups is not known.

Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical condition. Elevated liver biochemistry is found in 50% of patients with simple steatosis.^[5] The serum ALT level usually is greater than the AST level in non-alcoholic variant and the opposite in alcoholic FLD.

The treatment of fatty liver depends on what is causing it, and generally, treating the underlying cause will reverse the process of steatosis if implemented at early stage. Recent studies suggest that diet, exercise, and especially antiglycemic drugs may alter the course of the disease. A randomized controlled trial found that pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis.^[6]

Avoidance of alcohol abuse, maintenance of health diet and weight helps in preventing fatty liver.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Fatty liver is the fatty degeneration of the parenchymal cells causing a yellow discoloration of the liver. It is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis. Despite having multiple causes, fatty liver disease (FLD) can be considered a single disease that occurs worldwide in those with excessive alcohol intake and those who are obese (with or without effects of insulin resistance). The condition is also associated with other diseases that influence fat metabolism.^[1] Morphologically it is difficult to distinguish alcoholic FLD from non alcoholic FLD and both show micro-vesicular and macrovesicular fatty changes at different stages.

Fatty change represents the intra-cytoplasmic accumulation of triglyceride (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus – microvesicular fatty change. In this stage liver cells are filled with multiple fat droplets that do not displace centrally located nucleus. In the late stages, the size of the vacuoles increases pushing the nucleus to the periphery of the cell giving characteristic signet ring appearance – macrovesicular fatty change. These vesicles are well delineated and optically “empty” because fats dissolve during tissue processing. Large vacuoles may coalesce, producing fatty cysts – which are irreversible lesions. Macrovesicular steatosis is the most common form and is typically associated with alcohol, diabetes, obesity and corticosteroids. Acute fatty liver of pregnancy and Reye’s syndrome are examples of severe liver disease caused by microvesicular fatty change.^[2] The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight.^[3][4][1]

Defects in fat metabolism is responsible for pathogenesis of 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 from adipose tissue to the liver is increased.^[5][1] Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute towards fat accumulation. In addition alcoholism is known to damage mitochondria and other cellular structure further impairing cellular energy mechanism. On the other hand non alcoholic FLD may begin as excess of unmetabolized energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if there is cessation or removal of underlying cause.

Severe fatty liver is accompanied by inflammation, a situation that is referred to as steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH) depends on the persistence or severity of the inciting cause. Pathological lesions in both conditions are similar. However, the extent of inflammatory response varies widely and does not always correlate with the degree of fat accumulation. Steatosis (retention of lipid) and onset of steatohepatitis may represent successive stages in FLD progression.^[6]

Liver with extensive inflammation and high degree of steatosis often progresses to more severe forms of the disease.^[7] Hepatocyte ballooning and hepatocyte necrosis of varying degree are often present at this stage. Liver cell death and inflammatory responses lead to the activation of stellate cells which play a pivotal role in hepatic fibrosis. The extent of fibrosis varies widely. Perisinusoidal fibrosis is most common, especially in adults, and predominates in zone 3 around the terminal hepatic veins.^[8]

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.

Steatohepatitis is characterized microscopically by hepatic fat accumulation (steatosis), mixed lobular inflammation, ballooning degeneration of hepatocytes (sometimes with identifiable Mallory bodies), glycogenated hepatocyte nuclei, and pericellular fibrosis. The “chicken wire” pattern of the pericellular fibrosis, which affects portal areas only secondarily in later stages, is very characteristic and is identified on trichrome stains.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Fatty liver is commonly associated with alcohol or metabolic syndrome (diabetes, hypertension and dyslipidemia) but can also be due to any one of many causes:^[1][2]

• Metabolic: Abetalipoproteinemia, glycogen storage diseases, Weber-Christian disease, Wolmans disease, acute fatty liver of pregnancy, lipodystrophy
• Nutritional: Malnutrition, total parenteral nutrition, severe weight loss, refeeding syndrome, jejuno-ileal bypass, gastric bypass, jejunal diverticulosis with bacterial overgrowth
• Drugs and toxins: Amiodarone, methotrexate, diltiazem, highly active antiretroviral therapy, glucocorticoids, tamoxifen, environmental hepatotoxins (e.g. phosphorus, toxic mushroom)
• Other: Inflammatory bowel disease, HIV

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

• Abetalipoproteinemia
• Aryl-dehydrogenase deficiency
• Cystic fibrosis
• Diabetes mellitus
• Disorders of lipid metabolism
• Drugs, toxins
• Fructose intolerance
• Galactose metabolism
• Glycogen metabolism
• Homocystine metabolism
• Inflammatory bowel disease
• Intestinal bypass surgery
• Obesity
• Parenteral nutrition
• Pregnancy
• Protein malnutrition, deficiency
• Refsum’s disease
• Reye’s syndrome
• Starvation, rapid weight loss
• Tyrosine metabolism
• Weber-Christian Disease
• Wilson’s disease^[3]

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Please help WikiDoc by adding more content here. It’s easy! Click here to learn about editing.

Fatty liver disease is prevalent among 10%- 24% of general population in various countries.^[1] However among obese individuals the condition is observed in up to 75% of people, 35% of whom, despite no evidence of excessive alcohol consumption, will lead to non alcoholic FLD.^[2] It is the most common cause of abnormal liver function test in the US.^[1] African Americans and Mexican Americans have higher frequencies of unexplained serum aminotransferase elevations than those reported in whites but prevalence of FLD among different racial groups is not known.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

• Overweight (body mass index of 25-30)
• Obesity
• Diabetes
• High triglycerides
• Alcohol abuse
• Rapid weight loss
• Malnutrition

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Per the American Gastroenterological Association (AGA) in 2021^[1], screening should be:

• Diabetes mellitus Type 2
• 2 or more metabolic risk factors (entral obesity, high triglycerides, low HDL cholesterol, hypertension, prediabetes, or insulin resistance)
• Excessive alcohol intake
• Steatosis on any imaging modality or elevated aminotransferases

Per the American Association for the Study of Liver Diseases (AASLD) in 2023^[2]:

• “All patients with hepatic steatosis or clinically suspected NAFLD based on the presence of obesity and metabolic risk factors should undergo primary risk assessment with FIB-4.”

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Up to 10% of cirrhotic alcoholic FLD will develop hepatocellular carcinoma. Overall incidence of liver cancer in non-alcoholic FLD has not been assessed yet but the association is well established.^[1]

A retrospective cohort study concluded that liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis.^[2]

• http://nafldscore.com/

Prognosis can be determined by:

• FIB-4
• Liver stiffness measurement
  • Vibration-controlled elastography (VCTE), Fibroscan

• • Magnetic resonance elastography (MRE)