The percentage of people with non-alcoholic fatty liver disease ranges from 9 to 36.9% in different parts of the world. Approximately 20% of the United States population have non-alcoholic fatty liver, and the number of people affected is increasing. This means about 75 to 100 million people in the United States are affected.

The rates of non-alcoholic fatty liver disease is higher in Hispanics, which can be attributed to high rates of obesity and type 2 diabetes in Hispanic populations. Non-alcoholic fatty liver disease is also more common among men than women in all age groups until age 60, where the prevalence between sex equalize. This is due to the protective nature of estrogen. Fatty liver and NASH occur all ages, with the highest rates in the 40- to 49-year-old age group. It is the most common liver abnormality in children ages 2 to 19.

Native American men have a high prevalence of non-alcoholic fatty liver disease. Two genetic mutations for this susceptibility have been identified, and these mutations provided clues to the mechanism of NASH and related diseases.

Polymorphisms (genetic variations) in the single-nucleotide polymorphisms (SNPs) T455C and C482T in APOC3 are associated with fatty liver disease, insulin resistance, and possibly hypertriglyceridemia. 95 healthy Asian Indian men and 163 healthy non-Asian Indian men around New Haven, Connecticut were genotyped for polymorphisms in those SNPs. 20% homogeneous wild both loci. Carriers of T-455C, C-482T, or both (not additive) had a 30% increase in fasting plasma apolipoprotein C3, 60% increase in fasting plasma triglyceride and retinal fatty acid ester, and 46% reduction in plasma triglyceride clearance. Prevalence of non-alcoholic fatty liver disease was 38% in carriers, 0% wild (normal). Subjects with fatty liver disease had marked insulin resistance.

The prevalence of FLD in the general population ranges from 10% to 24% in various countries. However, the condition is observed in up to 75% of obese people, 35% of whom progress to NAFLD, despite no evidence of excessive alcohol consumption. FLD is the most common cause of abnormal liver function tests in the United States. "Fatty livers occur in 33% of European-Americans, 45% of Hispanic-Americans, and 24% of African-Americans."

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

- Metabolic: abetalipoproteinemia, glycogen storage diseases, Weber–Christian disease, acute fatty liver of pregnancy, lipodystrophy

- Nutritional:malnutrition, total parenteral nutrition, severe weight loss, refeeding syndrome, jejunoileal bypass, gastric bypass, jejunal diverticulosis with bacterial overgrowth

- Drugs and toxins: amiodarone, methotrexate, diltiazem, expired tetracycline, highly active antiretroviral therapy, glucocorticoids, tamoxifen, environmental hepatotoxins (e.g., phosphorus, mushroom poisoning)

- Alcohol: Alcoholism is one of the major causes of fatty liver due to production of toxic metabolites like aldehydes during metabolism of alcohol in the liver. This phenomenon most commonly occurs with chronic alcoholism.

- Other: celiac disease, inflammatory bowel disease, HIV, hepatitis C (especially genotype 3), and alpha 1-antitrypsin deficiency

Non-alcoholic steatohepatitis is fatty liver disease due to causes other than alcohol. No pharmacological treatment has received approval as of 2015 for NASH. Some studies suggest diet, exercise, and antiglycemic drugs may alter the course of the disease. General recommendations include improving metabolic risk factors and reducing alcohol intake. NASH was first described in 1980 in a series of patients of the Mayo Clinic. Its relevance and high prevalence were recognized mainly in the 1990s. Some think NASH is a diagnosis of exclusion, and many cases may in fact be due to other causes.

Key prevention strategies for cirrhosis are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns, and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.

Little is known about factors affecting cirrhosis risk and progression. Research has suggested that coffee consumption appears to help protect against cirrhosis.

Hepatocellular carcinoma is a primary liver cancer that is more common in people with cirrhosis. People with known cirrhosis are often screened intermittently for early signs of this tumor, and screening has been shown to improve outcomes.

The risk factors presently known are:

- Quantity of alcohol taken: Consumption of 60–80g per day (14g is considered one standard drink in the USA, i.e., 1.5 fl oz hard liquor, 5 fl oz wine, 12 fl oz beer; drinking a six-pack of beer daily would be in the middle of the range) for 20 years or more in men, or 20g/day for women significantly increases the risk of hepatitis and fibrosis by 7% to 47%,

- Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease.

- Gender: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in fat absorption due to the menstrual cycle may explain this phenomenon.

- Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury.

- Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease.

- Iron overload (Hemochromatosis)

- Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.

The prognosis for people with ALD depends on the liver histology as well as cofactors, such as concomitant chronic viral hepatitis. Among patients with alcoholic hepatitis, progression to liver cirrhosis occurs at 10–20% per year, and 70% will eventually develop cirrhosis. Despite cessation of alcohol use, only 10% will have normalization of histology and serum liver enzyme levels. As previously noted, the MDF has been used to predict short-term mortality (i.e., MDF ≥ 32 associated with spontaneous survival of 50–65% without corticosteroid therapy, and MDF 11) and 90-day (MELD > 21) mortality. Liver cirrhosis develops in 6–14% of those who consume more than 60–80 g of alcohol daily for men and more than 20 g daily for women. Even in those who drink more than 120 g daily, only 13.5% will suffer serious alcohol-related liver injury. Nevertheless, alcohol-related mortality was the third leading cause of death in 2003 in the United States. Worldwide mortality is estimated to be 150,000 per year.

Macrovesicular steatosis is the more common form of fatty degeneration and may be caused by oversupply of lipids due to obesity, obstructive sleep apnea (OSA), insulin resistance, or alcoholism. Nutrient malnutrition may also cause the mobilisation of fat from adipocytes and create a local oversupply in the liver where lipid metabolism occurs. Excess alcohol over a long period of time can induce steatosis. The breakdown of large amounts of ethanol in alcoholic drinks produces large amounts of chemical energy, in the form of NADH, signalling to the cell to inhibit the breakdown of fatty acids (which also produces energy) and simultaneously increase the synthesis of fatty acids. This "false sense of energy" results in more lipid being created than is needed.

Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes.

There are two main types of fatty liver disease: alcohol-related fatty liver disease and non-alcoholic fatty liver disease (NAFLD). Risk factors for NAFLD include diabetes, obesity and metabolic syndrome. When inflammation is present it is referred to as alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Steatohepatitis of either cause may progress to cirrhosis, and NASH is now believed to be a frequent cause of unexplained cirrhosis (at least in Western societies). NASH is also associated with lysosomal acid lipase deficiency.

The word is from "steato-", meaning "fat" and "hepatitis", meaning "inflammation of the liver".

No single mechanism leading to steatosis exists; rather, a varied multitude of pathologies disrupt normal lipid movement through the cell and cause accumulation. These mechanisms can be separated on whether they ultimately cause an oversupply of lipid which can not be removed quickly enough (i.e., too much in), or whether they cause a failure in lipid breakdown (i.e., not enough used).

Failure of lipid metabolism can also lead to the mechanisms which would normally utilise or remove lipids becoming impaired, resulting in the accumulation of unused lipids in the cell. Certain toxins, such as alcohols, carbon tetrachloride, aspirin, and diphtheria toxin, interfere with cellular machinery involved in lipid metabolism. In those with Gaucher's disease, the lysosomes fail to degrade lipids and steatosis arises from the accumulation of glycolipids. Protein malnutrition, such as that seen in kwashiorkor, results in a lack of precursor apoproteins within the cell, therefore unused lipids which would normally participate in lipoprotein synthesis begin to accumulate.

Liver disease can occur through several mechanisms. A common form of liver disease is viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by HBV DNA, but testing for HBsAg is negative. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the liver's cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma.

According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter.

There are more than a hundred different kinds of liver disease. Symptoms may include jaundice and weight loss. These are some of the most common:

- Fascioliasis, a parasitic infection of liver caused by a Liver fluke of the "Fasciola" genus, mostly the "Fasciola hepatica".

- Hepatitis, inflammation of the liver, is caused by various viruses (viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity (autoimmune hepatitis) or hereditary conditions.

- Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, and cirrhosis. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.

- Fatty liver disease (hepatic steatosis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells. Non-alcoholic fatty liver disease is a spectrum of disease associated with obesity and metabolic syndrome.

- Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of iron in the body, and Wilson's disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II.

- In transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative and/or cardiopathic effects. Liver transplantation can give a curative treatment option.

- Gilbert's syndrome, a genetic disorder of bilirubin metabolism found in a small percent of the population, can cause mild jaundice.

- Cirrhosis is the formation of fibrous tissue (fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic liver failure.

- Primary liver cancer most commonly manifests as hepatocellular carcinoma and/or cholangiocarcinoma; rarer forms include angiosarcoma and hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)

- Primary biliary cirrhosis is a serious autoimmune disease of the bile capillaries.

- Primary sclerosing cholangitis is a serious chronic inflammatory disease of the bile duct, which is believed to be autoimmune in origin.

- Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein.

Acute fatty liver of pregnancy is a rare condition and occurs in approximately one in 7,000 to one in 15,000 pregnancies. The mortality from acute fatty liver of pregnancy has been reduced significantly to 18%, and is now related primarily to complications, particularly DIC (Disseminated Intravascular Coagulation) and infections. After delivery, most mothers do well, as the stimulus for fatty acid overload is removed. The disease can recur in future pregnancies, with a calculated genetic chance of 25%; the actual rate is lower, however. Mortality of the foetus has also diminished significantly, but still remains 23%, and may be related to the need for premature delivery.

In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In acetaminophen toxicity, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.

An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hy's Law). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.

Glucocorticoids are so named due to their effect on the carbohydrate mechanism. They promote glycogen storage in the liver. An enlarged liver is a rare side-effect of long-term steroid use in children. The classical effect of prolonged use both in adult and paediatric population is steatosis.

Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis. The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. Toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disruption of cell metabolism, and causing structural changes. Some drugs such as paracetamol exhibit predictable dose-dependent liver damage while others such as isoniazid cause idiosyncratic and unpredictable reactions that vary among individuals. There are wide variations in the mechanisms of liver injury and latency period from exposure to development of clinical illness.

Many types of drugs can cause liver injury, including the analgesic paracetamol; antibiotics such as isoniazid, nitrofurantoin, amoxicillin-clavulanate, erythromycin, and trimethoprim-sulfamethoxazole; anticonvulsants such as valproate and phenytoin; cholesterol-lowering statins; steroids such as oral contraceptives and anabolic steroids; and highly active anti-retroviral therapy used in the treatment of HIV/AIDS. Of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and paracetamol toxicity the most common cause of acute liver failure in the United States and Europe.

Herbal remedies and dietary supplements are another important cause of hepatitis; these are the most common causes of drug-induced hepatitis in Korea. The United-States-based Drug Induced Liver Injury Network linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements. In the United States, herbal and dietary supplements – unlike pharmaceutical drugs – are unregulated by the Food and Drug Administration. However, the National Institutes of Health maintains the LiverTox database for consumers to track all known prescription and non-prescription compounds associated with liver injury.

Exposure to other hepatotoxins can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. The industrial toxin carbon tetrachloride and the wild mushroom Amanita phalloides are other known hepatotoxins.

Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure. People in these groups who are not already immune can receive the hepatitis A vaccine.

Those at high risk and in need of screening include:

- People with poor sanitary habits such as not washing hands after using the restroom or changing diapers

- People who do not have access to clean water

- People in close contact (either living with or having sexual contact) with someone who has hepatitis A

- Illicit drug users

- People with liver disease

- People traveling to an area with endemic hepatitis A

The presence of anti-hepatitis A IgG in the blood indicates past infection with the virus or prior vaccination.

Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the mother, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis.

Testing the general population under the age of 40 without symptoms is of unclear benefit.

Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:

- diabetes mellitus

- Use of drugs such as thiazide diuretics, beta blockers, and estrogens

Other conditions leading to acquired hyperlipidemia include:

- Hypothyroidism

- Kidney failure

- Nephrotic syndrome

- Alcohol consumption

- Some rare endocrine disorders and metabolic disorders

Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.

Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.

Left untreated, Wilson's disease tends to become progressively worse and is eventually fatal. With early detection and treatment, most of those affected can live relatively normal lives. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent.

In general, a diet low in copper-containing foods is recommended with the avoidance of mushrooms, nuts, chocolate, dried fruit, liver, and shellfish.

Some children with LAL-D have had an experimental therapy called hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplant, to try to prevent the disease from getting worse. Data are sparse but there is a known high risk of serious complications including death, graft-versus-host disease.