Fatty liver is a reversible condition wherein large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis (i.e., abnormal retention of lipids within a cell). Despite having multiple causes, fatty liver can be considered a single disease that occurs worldwide in those with excessive alcohol intake and the obese (with or without effects of insulin resistance). The condition is also associated with other diseases that influence fat metabolism. When this process of fat metabolism is disrupted, the fat can accumulate in the liver in excessive amounts, thus resulting in a fatty liver. It is difficult to distinguish alcoholic FLD, which is part of alcoholic liver disease, from nonalcoholic FLD (NAFLD), and both show microvesicular and macrovesicular fatty changes at different stages.

The accumulation of fat in alcoholic or non-alcoholic steatosis may also be accompanied by a progressive inflammation of the liver (hepatitis), called steatohepatitis. This more severe condition may be termed either alcoholic steatohepatitis or non-alcoholic steatohepatitis (NASH).

Most people with NAFLD have few or no symptoms. Patients may complain of fatigue, malaise, and dull right-upper-quadrant abdominal discomfort. Mild jaundice may be noticed, although this is rare. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day (about 25 ml/day of net ethanol) excludes the condition.

NAFLD is associated with insulin resistance and metabolic syndrome (obesity, combined hyperlipidemia, diabetes mellitus (type II), and high blood pressure).

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

Acute liver failure is defined as "the rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient without known prior liver disease".

The disease process is associated with the development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. The diagnosis of acute liver failure is based on physical exam, laboratory findings, patient history, and past medical history to establish mental status changes, coagulopathy, rapidity of onset, and absence of known prior liver disease respectively.

The exact definition of "rapid" is somewhat questionable, and different sub-divisions exist which are based on the time from onset of first hepatic symptoms to onset of encephalopathy. One scheme defines "acute hepatic failure" as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This is sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks. Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks.

Non-alcoholic fatty liver disease (NAFLD) is one of the types of fatty liver which occurs when fat is deposited (steatosis) in the liver due to causes other than excessive alcohol use. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD. NAFLD is the most common liver disorder in developed countries.

NAFLD is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states (e.g. diabetes mellitus type 2) such as weight loss, metformin, and thiazolidinediones. Up to 80% of obese people have the disease. NASH is regarded as a major cause of cirrhosis of the liver of unknown cause. Most people have a good outcome if the condition is caught in its early stages.

About 12 to 25% of people in the United States have NAFLD, while NASH affects between 2 and 5% of people in the United States.

Chronic liver failure usually occurs in the context of cirrhosis, itself potentially the result of many possible causes, such as excessive alcohol intake, hepatitis B or C, autoimmune, hereditary and metabolic causes (such as iron or copper overload, steatohepatitis or non-alcoholic fatty liver disease).

Liver disease (also called hepatic disease) is a type of damage to or disease of the liver.

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.

Type 1 tyrosinemia typically presents in infancy as failure to thrive and hepatomegaly. The primary effects are progressive liver and kidney dysfunction. The liver disease causes cirrhosis, conjugated hyperbilirubinemia, elevated AFP, hypoglycemia and coagulation abnormalities. This can lead to jaundice, ascites and hemorrhage. There is also an increased risk of hepatocellular carcinoma.

The kidney dysfunction presents as Fanconi syndrome: Renal tubular acidosis, hypophosphatemia and aminoaciduria. Cardiomyopathy, neurologic and dermatologic manifestations are also possible. The urine has an odor of cabbage or rancid butter.

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".

Signs of chronic liver disease detectable on clinical examination can be divided into those that are associated with the diagnosis of chronic liver disease, associated with decompensation and associated with the cause.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation (chronic hepatitis), liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

Intestinal involvement can cause mild malabsorption with steatorrhea, greasy stools, but usually requires no treatment.

Hypoglycemia is the central clinical problem, the one that is most damaging, and the one that most often prompts the initial diagnosis.

Maternal glucose transferred across the placenta prevents hypoglycemia in a fetus with GSD I, but the liver is enlarged with glycogen at birth. The inability to generate and release glucose soon results in hypoglycemia, and occasionally in lactic acidosis fulminant enough to appear as a primary respiratory problem in the newborn period. Neurological manifestations are less severe than if the hypoglycemia were more acute. The brain's habituation to mild hypoglycemia is at least partly explained by use of alternative fuels, primarily lactate.

More commonly, infants with GSD I tolerate without obvious symptoms a chronic, mild hypoglycemia, and compensated lactic acidosis between feedings. Blood glucose levels are typically 25 to 50 mg/dl (1.4–2.8 mM). These infants continue to need oral carbohydrates every few hours. Many never sleep through the night even in the second year of life. They may be pale, clammy, and irritable a few hours after a meal. Developmental delay is not an intrinsic or inevitable effect of glucose-6-phosphatase deficiency but is common if the diagnosis is not made in early infancy.

Although mild hypoglycemia for much of the day may go unsuspected, the metabolic adaptations described above make severe hypoglycemic episodes, with unconsciousness or seizure, uncommon before treatment. Episodes which occur are likely to happen in the morning before breakfast. GSD I is therefore a potential cause of ketotic hypoglycemia in young children.

Once the diagnosis has been made, the principal goal of treatment is to maintain an adequate glucose level and prevent hypoglycemia.

Symptoms having to do with hepatomegaly can include several, among them the individual may experience some weight loss, poor appetite and lethargy (jaundice and bruising may also be present)

The most common clinical history in patients with glycogen-storage disease type 0 (GSD-0) is that of an infant or child with symptomatic hypoglycemia or seizures that occur before breakfast or after an inadvertent fast. In affected infants, this event typically begins after they outgrow their nighttime feeds. In children, this event may occur during acute GI illness or periods of poor enteral intake.

Mild hypoglycemic episodes may be clinically unrecognized, or they may cause symptoms such as drowsiness, sweating, lack of attention, or pallor. Uncoordinated eye movements, disorientation, seizures, and coma may accompany severe episodes.

Glycogen-storage disease type 0 affects only the liver. Growth delay may be evident with height and weight percentiles below average. Abdominal examination findings may be normal or reveal only mild hepatomegaly.Signs of acute hypoglycemia may be present, including the following:

The mechanism of hepatomegaly consists of vascular swelling, inflammation (due to the various causes that are infectious in origin) and deposition of (1) non-hepatic cells or (2) increased cell contents (such due to iron in hemochromatosis or hemosiderosis and fat in fatty liver disease)

Type 1 tyrosinemia, also known as hepatorenal tyrosinemia or tyrosinosis, is the most severe form of tyrosinemia, a buildup of too much of the amino acid tyrosine in the blood and tissues due to an inability to metabolize it. It is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase.

Sitosterolemia may share several clinical characteristics with the well-characterized familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis . However, in contrast to FH patients, sitosterolemia patients usually have normal to moderately elevated total sterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol, avenosterol) and 5α-saturated stanols in their plasma. Plasma sitosterol levels in sitosterolemia patients are 10–25 times higher than in normal individuals (8–60 mg/dl). Not all patients with sitosterolemia have tendon xanthomas, thus absence of this should not be used to exclude this diagnosis.

Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (e.g., Achilles tendon, extensor tendons of the hand) in children and adults. Xanthelasma and corneal arcus are less common. Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present.In addition, sitosterolemia patients may develop hemolytic episodes and splenomegaly.

Untreated, the condition causes a significant increase in morbidity and mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in untreated patients.

This condition is suspected to result in liver dysfunction and cirrhosis, in the context of sitosterolemia, is reported

Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme (GYS). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. There are two isoforms (types) of glycogen synthase enzyme; GYS1 in muscle and GSY2 in liver, each with a corresponding form of the disease. Mutations in the liver isoform (GYS2), causes fasting hypoglycemia, high blood ketones, increased free fatty acids and low levels of alanine and lactate. Conversely, feeding in these patients results in hyperglycemia and hyperlactatemia.

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.

Glycogen storage disease type III presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later. The liver pathology typically regresses as the individual enter adolescence, as does splenomegaly, should the individual so develop it.

The presentation of this disorder entails anemia, arthritis, hepatic anomalies, and recurrent infections are clinical signs of the disease. Iron overload occurs mainly in the liver, heart, pancreas, thyroid, and kidney

This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), “probable” (score 6-8), “possible” (score 3-5), “unlikely” (score 1-2) and “excluded” (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in amoxycillin-clauvonic acid ).

Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present either with worsening of symptoms or may be without symptoms at the time of cancer detection. HCC may directly present with yellow skin, abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.