Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver biochemistry is found in 50% of patients with simple steatosis. The serum alanine transaminase level usually is greater than the aspartate transaminase level in the nonalcoholic variant and the opposite in alcoholic FLD (AST:ALT more than 2:1).

Imaging studies are often obtained during the evaluation process. Ultrasonography reveals a "bright" liver with increased echogenicity. Medical imaging can aid in diagnosis of fatty liver; fatty livers have lower density than spleens on computed tomography (CT), and fat appears bright in T1-weighted magnetic resonance images (MRIs). No medical imagery, however, is able to distinguish simple steatosis from advanced NASH. Histological diagnosis by liver biopsy is sought when assessment of severity is indicated.

Common findings are elevated liver enzymes and a liver ultrasound showing steatosis. An ultrasound may also be used to exclude gallstone problems (cholelithiasis). A liver biopsy (tissue examination) is the only test widely accepted as definitively distinguishing NASH from other forms of liver disease and can be used to assess the severity of the inflammation and resultant fibrosis.

Non-invasive diagnostic tests have been developed, such as FibroTest, that estimates liver fibrosis, and SteatoTest, that estimates steatosis, however their use has not been widely adopted. Apoptosis has been indicated as a potential mechanism of hepatocyte injury as caspase-cleaved cytokeratin 18 (M30-Apoptosense ELISA) in serum/plasma is often elevated in patients with NASH and tests based on these parameters have been developed; however, as the role of oncotic necrosis has yet to be examined it is unknown to what degree apoptosis acts as the predominant form of injury.

Other diagnostic tests are available. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and kidney function. Because the liver is important for making proteins used in coagulation some coagulation related studies are often carried out especially the INR (international normalized ratio). In people with fatty liver with associated inflammatory injury (steatohepatitis) blood tests are usually used to rule out viral hepatitis (hepatitis A, B, C and herpes viruses like EBV or CMV), rubella, and autoimmune related diseases. Hypothyroidism is more prevalent in NASH patients which would be detected by determining the TSH.

It has been suggested that in cases involving overweight patients whose blood tests do not improve on losing weight and exercising that a further search of other underlying causes is undertaken. This would also apply to those with fatty liver who are very young or not overweight or insulin-resistant. In addition those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those that present with moderate to advanced fibrosis or cirrhosis.

The treatment of fatty liver depends on its cause, and, in general, treating the underlying cause will reverse the process of steatosis if implemented at an early stage. Two known causes of fatty liver disease are an excess consumption of alcohol and a prolonged diet containing foods with a high proportion of calories coming from lipids. For the patients with non-alcoholic fatty liver disease with pure steatosis and no evidence of inflammation, a gradual weight loss is often the only recommendation. In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those that induce weight loss have been shown to improve liver function.

For advanced patients with non-alcoholic steatohepatitis (NASH), there are no currently available therapies.

Up to 10% of people with cirrhotic alcoholic FLD will develop hepatocellular carcinoma. The overall incidence of liver cancer in nonalcoholic FLD has not yet been quantified, but the association is well-established.

Bariatric surgery, while not currently recommended as a treatment for fatty liver disease (FLD) alone, has been shown to revert FLD and advanced steatohepatitis in over 90% of people who have undergone this surgery for the treatment of obesity.

On X-ray computed tomography (CT), the increased fat component will decrease the density of the liver tissue, making the image less bright. Typically the density of the spleen and liver are roughly equivalent. In steatosis, there is a difference between the density and brightness of the two organs, with the liver appearing darker.

On ultrasound, fat is more echogenic (capable of reflecting sound waves). The combination of liver steatosis being dark on CT and bright on ultrasound is sometimes known as the flip flop sign.

On Magnetic Resonance Imaging, multiecho gradient echo images can be used to determine the percent fat fraction of the liver. The different resonance frequencies between water and fat make this technique very sensitive and accurate. Acquisition of echoes in "in phase" and "out phase" conditions (pertaining to the relative phases of the fat and water proton contingents) enables to obtain a signal proportional to the water and fat contingent, or a signal proportional to the water minus the fat contingent. These signal intensities are then algebraically combined into a percent fat. More recent techniques take into account experimental noise, signal decay and spectroscopic properties of fat. Numerous validation studies have demonstrated excellent correlations between the steatosis level quantified at MRI and the steatosis levels semi-quantitavely and quantitatively determined on liver biopsies (reference methods). Several MRI vendors offer automated calculation of percent fat with acquisition sequences no longer than a single breath hold.

Many drug candidates are in advanced clinical studies as : elafibranor, obeticholic acid.

Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Other liver findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. An enlarged spleen (splenomegaly), which normally measures less than 11–12 cm in adults, is suggestive of cirrhosis with portal hypertension, in the right clinical context. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension, and Budd-Chiari syndrome (by assessing flow in the hepatic vein).

Cirrhosis is diagnosed with a variety of elastography techniques. Because a cirrhotic liver is generally stiffer than a healthy one, imaging the liver's stiffness can give diagnostic information about the location and severity of cirrhosis. Techniques used include transient elastography, acoustic radiation force impulse imaging, supersonic shear imaging and magnetic resonance elastography. Compared to a biopsy, elastography can sample a much larger area and is painless. It shows a reasonable correlation with the severity of cirrhosis.

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP).

In the early stages, patients with ALD exhibits subtle and often no abnormal physical findings. It is usually not until development of advanced liver disease that stigmata of chronic liver disease become apparent. Early ALD is usually discovered during routine health examinations when liver enzyme levels are found to be elevated. These usually reflect alcoholic hepatic steatosis. Microvesicular and macrovesicular steatosis with inflammation are seen in liver biopsy specimens. These histologic features of ALD are indistinguishable from those of nonalcoholic fatty liver disease. Steatosis usually resolves after discontinuation of alcohol use. Continuation of alcohol use will result in a higher risk of progression of liver disease and cirrhosis. In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice, hepatomegaly, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation.Tender hepatomegaly may be present, but abdominal pain is unusual. Occasionally, the patient may be asymptomatic.

A number of liver function tests (LFTs) are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins, serum albumin, serum globulin,

alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.

Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to examine the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography may reduce the need for biopsy in some situations.

The severity of cirrhosis is commonly classified with the Child-Pugh score. This scoring system uses bilirubin, albumin, INR, the presence and severity of ascites, and encephalopathy to classify patients into class A, B, or C. Class A has a favourable prognosis, while class C is at high risk of death. This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others.

More modern scores, used in the allocation of liver transplants but also in other contexts, are the Model for End-Stage Liver Disease (MELD) score and its pediatric counterpart, the Pediatric End-Stage Liver Disease (PELD) score.

The hepatic venous pressure gradient, (difference in venous pressure between afferent and efferent blood to the liver) also determines the severity of cirrhosis, although it is hard to measure. A value of 16 mm or more means a greatly increased risk of death.

In people with alcoholic hepatitis, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is greater than 2:1.AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of pyridoxal-6-phosphate, which is required in the ALT enzyme synthetic pathway. Furthermore, alcohol metabolite–induced injury of hepatic mitochondria results in AST isoenzyme release. Other laboratory findings include red blood cell macrocytosis (mean corpuscular volume > 100) and elevations of serum γ-glutamyl transferase, alkaline phosphatase, and bilirubin levels. Folate level is reduced in alcoholic patients due to decreased intestinal absorption, increased bone marrow requirement for folate in the presence of alcohol, and increased urinary loss.The magnitude of leukocytosis reflects severity of liver injury. Histologic features include Mallory bodies, giant mitochondria, hepatocyte necrosis, and neutrophil infiltration at the perivenular area. Mallory bodies, which are also present in other liver diseases, are condensations of cytokeratin components in the hepatocyte cytoplasm and do not contribute to liver injury.Up to 70% of patients with moderate to severe alcoholic hepatitis already have cirrhosis identifiable on biopsy examination at the time of diagnosis.

Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:

- By using steroid-based drugs in autoimmune hepatitis.

- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.

- Wilson’s disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.

- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.

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 ).

Histologically, steatosis is physically apparent as lipid within membrane bound liposomes of parenchymal cells. When this tissue is fixed and stained to be better viewed under a microscope, the lipid is usually dissolved by the solvents used to prepare the sample. As such, samples prepared this way will appear to have empty holes (or vacuoles) within the cells where the lipid has been cleared. Special lipid stains, such as Sudan stains and osmium tetroxide are able to retain and show up lipid droplets, hence more conclusively indicating the presence of lipids. Other intracellular accumulations, such as water or glycogen, can also appear as clear vacuoles, therefore it becomes necessary to use stains to better decide what is accumulating.

Grossly, steatosis causes organ enlargement and lightening in colour. This is due to the high lipid content increasing the organ's volume and becoming visible to the unaided eye. In severe cases, the organ may become vastly enlarged, greasy, and yellow in appearance.

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.

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.

If a liver biopsy is needed for diagnosis of the condition, the mother should be appropriately stabilized and treated to reduce bleeding related complications. The diagnosis can be made by a frozen-section (as opposed to a specimen in formalin) that is stained with the Oil red O stain, that shows microvesicular steatosis (or small collections of fat within the liver cells). The microvesicular steatosis usually spares zone one of the liver, which is the area closest to the hepatic artery. On the regular trichrome stain, the liver cell cytoplasm shows a foamy appearance due to the prominence of fat. Necrosis is rarely seen. The diagnosis can be enhanced by electron microscopy which can be used to confirm the presence of microvesicular steatosis, and specifically the presence of megamitochondria and paracrystalline inclusions. Liver diseases with similar appearances include Reye's syndrome, drug-induced hepatitis from agents with mitochondrial toxicity, including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting sickness which is caused by the eating of the unripened Ackee fruit.

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".

The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible. This allows for early treatment, which can prevent disease progression, and decreases transmission to others.

The diagnosis of acute fatty liver of pregnancy is usually made on clinical grounds by the treating physician or midwife, but differentiation from other conditions affecting the liver may be difficult. The diagnosis of acute fatty liver of pregnancy is suggested by jaundice with a lesser elevation of liver enzymes, elevated white blood cell count, disseminated intravascular coagulation, and a clinically unwell patient.

A liver biopsy can provide a definitive diagnosis, but is not always done, due to the increased chance of bleeding in acute fatty liver of pregnancy. Often testing will be done to exclude more common conditions that present in a similar fashion, including viral hepatitis, pre-eclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and autoimmune hepatitis.

Diagnosis of hepatitis is made on the basis of some or all of the following: a patient's signs and symptoms, medical history including sexual and substance use history, blood tests, imaging, and liver biopsy. In general, for viral hepatitis and other acute causes of hepatitis, the patient's blood tests and clinical picture are sufficient for diagnosis. For other causes of hepatitis, especially chronic causes, blood tests may not be useful. In this case, liver biopsy is the gold standard for establishing the diagnosis as histopathologic analysis is able to reveal the precise extent and pattern of inflammation and fibrosis. However, liver biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in patients with liver injury and cirrhosis.

Blood testing includes liver enzymes, serology (i.e. for autoantibodies), nucleic acid testing (i.e. for hepatitis virus DNA/RNA), blood chemistry, and complete blood count. Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis. Generally, AST and ALT are elevated in most cases of hepatitis regardless of whether the patient shows any symptoms. However, the degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis.

Ultrasound, CT, and MRI can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis. CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver. Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis. Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver.

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

Mutation analysis of the "ATP7B" gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, it is possible to screen family members for the disease as part of clinical genetics family counseling. Regional distributions of genes associated with Wilson's disease are important to follow, as this can help clinicians design appropriate screening strategies. Since mutations of the WD gene vary between populations, research and genetic testing done in countries like the USA or United Kingdom can pose problems as they tend to have more mixed populations.

Once other investigations have indicated Wilson's disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. This is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 μg of copper per gram of dried liver tissue confirms Wilson's disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilson's.

In the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas of necrosis (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis.

The initial workup of abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially.

Acanthocytes are seen on blood smear. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.

The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic.

There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.

For treatment of type II, dietary modification is the initial approach, but many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrates (peroxisome proliferator-activated receptor-alpha agonists) may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy and rhabdomyolysis, so is only done under close supervision. Other agents commonly added to statins are ezetimibe, niacin, and bile acid sequestrants. Dietary supplementation with fish oil is also used to reduce elevated triglycerides, with the greatest effect occurring in patients with the greatest severity. Some evidence exists for benefit of plant sterol-containing products and omega-3 fatty acids.