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.

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).

Ultrasonography (US) is the first-line imaging technique for the diagnosis and follow-up of portal hypertension because it is non-invasive, low-cost and can be performed on-site.

Signs of portal hypertension on ultrasound include dilatation of the portal vein of over 13 mm in diameter, a portal flow mean velocity of less than 12 cm/s on Doppler ultrasound, porto–systemic collateral veins (patent paraumbilical vein, spleno–renal collaterals and dilated left and short gastric veins), splenomegaly and signs of cirrhosis (including nodularity of the liver surface).

The hepatic venous pressure gradient (HVPG) measurement has been accepted as the gold standard for assessing the severity of portal hypertension. Portal hypertension is defined as HVPG greater than or equal to 5 mm Hg and is considered to be clinically significant when HVPG exceeds 10 to 12 mm Hg.

Symptoms of congenital PSS usually appear by six months of age and include failure to gain weight, vomiting, and signs of hepatic encephalopathy (a condition where toxins normally removed by the liver accumulate in the blood and impair the function of brain cells) such as seizures, depression, tremors, drooling, and head pressing. Urate bladder stones may form because of increased amounts of uric acid in circulation and excreted by the kidneys. Initial diagnosis of PSS is through laboratory bloodwork showing either elevated serum bile acids after eating or elevation of fasting blood ammonia levels, which has been shown to have a higher sensitivity and specificity than the bile acids test.

Various diagnostic imaging techniques are used to demonstrate PSS. Ultrasonography is a rapid, convenient, non-invasive, and accurate method for diagnosis of PSS. Ultrasonographic diagnosis of congenital PSS depends on finding an anomalous vessel either in the liver or just caudal to the liver in the dorsal abdomen, usually draining into the caudal vena cava. Ultrasonography can also be used to estimate hepatic volume and vascularity, and to identify related lesions affecting other abdominal structures, such as urinary calculi. Computed tomography (CT) may be considered when ultrasound expertise is lacking or ultrasonography is considered sub-optimal (e.g. because of the conformation of the patient). Control of respiration and careful timing of CT acquisition after contrast injection is necessary for optimal depiction of PSS. Rectal portal scintigraphy using technetium pertechnetate, a technique of imaging involving detection of gamma rays emitted by radionuclides absorbed through the rectum and into the bloodstream, demonstrates the blood vessel bypassing the liver. In certain institutions, scintigraphy is the preferred diagnostic technique, but this leaves the patient radioactive for 24h, which may be inconvenient depending on nursing needs. Portal venography is the definitive method for demonstrating PSS, but is invasive, hence it is best reserved for animals with a known shunt or those considered highly likely to have a shunt that was not detectable by ultrasonography.

Blood tests should be done, importantly liver-function series, which will give a good impression of the patient's broad metabolic picture.

A complete blood test can help distinguish intrinsic liver disease from extrahepatic bile-duct obstruction. An ultrasound of the liver can reliably detect a dilated biliary-duct system,

it can also detect the characteristics of a cirrhotic liver.Computerized tomography (CT) can help to obtain accurate anatomical information, in individuals with hepatomegaly.

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.

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

The diagnosis of portal vein thrombosis is usually made by ultrasound, computed tomography with contrast or magnetic resonance imaging. D-dimer levels in the blood may be elevated as a result of fibrin degradation.

Selective shunts select non-intestinal flow to be shunted to the systemic venous drainage while leaving the intestinal venous drainage to continue to pass through the liver. The most well known of this type is the splenorenal. This connects the splenic vein to the left renal vein thus reducing portal system pressure while minimizing any encephalopathy. In an H-shunt, which could be mesocaval (from the superior mesenteric vein to the inferior vena cava) or could be, portocaval (from the portal vein to the inferior vena cava) a graft, either synthetic or the preferred vein harvested from somewhere else on the patient's body, is connected between the superior mesenteric vein and the inferior vena cava. The size of this shunt will determine how selective it is.

It should be noted that with the advent of transjugular intrahepatic portosystemic shunting (TIPS), portosystemic shunts are less performed. TIPS has the advantage of being easier to perform and doesn't disrupt the liver's vascularity.

Hepatic doppler ultrasound is typically utilized to confirm or suggest the diagnosis. Most common findings on liver doppler ultrasound include increased phasicity of portal veins with eventual development of portal flow reversal. The liver is usually enlarged but maintained normal echogenicity. A liver biopsy is required for a definitive diagnosis.

On microscopic examination of liver biopsy specimens, PBC is characterized by interlobular bile duct destruction. These histopathologic findings in primary biliary cholangitis include the following:

- Inflammation of the bile ducts, characterized by intraepithelial lymphocytes, and

- Periductal epithelioid granulomata.

When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers (creatinine, urea, electrolytes, LDH).

Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reye's syndrome.

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.

Hallmark of the disease is thrombosis/sclerosis of branches of portal vein. Vessels formed are often termed as mesangiosinusoids or periportal cavernoma.

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.

Treatment is directed largely to removing the cause, or, where that is impossible, to modifying its effects. Thus, therapy aimed at improving right heart function will also improve congestive hepatopathy. True nutmeg liver is usually secondary to left-sided heart failure causing congestive right heart failure, so treatment options are limited.

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.

It is characterized by 'obliterative portovenopathy', which leads to various problems such as portal hypertension, massive splenomegaly, and variceal bleeding. It is estimated that about 85% of people with NCPF have repeated episodes of variceal bleeding.

To diagnose PBC, it needs to be distinguished from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).

- Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase (ALP) are found in early disease. Elevations in bilirubin occur in advanced disease.

- Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90%-95% of patients and only 1% of controls. PBC patients have AMA against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. Those people who are AMA negative but with disease similar to PBC have been found to have AMAs when more sensitive detection methods are employed.

- Other auto-antibodies may be present:

- Abdominal ultrasound, MR scanning (MRCP) or a CT scan is usually performed to rule out blockage to the bile ducts. This may be needed if a condition causing secondary biliary cirrhosis, such as other biliary duct disease or gallstones, needs to be excluded. A liver biopsy may help, and if uncertainty remains as in some patients, an endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic investigation of the bile duct, may be performed.

Most patients can be diagnosed without invasive investigation, as the combination of anti-mitochondrial antibodies and typical (cholestatic) liver enzyme tests are considered diagnostic. However, a liver biopsy is needed to determine the stage of disease.

Biochemical markers include a normal GGT for PFIC-1 and -2, with a markedly elevated GGT for PFIC-3. Serum bile acid levels are grossly elevated. Serum cholesterol levels are typically not elevated, as is seen usually in cholestasis, as the pathology is due to a transporter as opposed to an anatomical problem with biliary cells.

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.

Routine complete blood count (CBC), basic metabolic profile, liver enzymes, and coagulation should be performed. Most experts recommend a diagnostic paracentesis be performed if the ascites is new or if the patient with ascites is being admitted to the hospital. The fluid is then reviewed for its gross appearance, protein level, albumin, and cell counts (red and white). Additional tests will be performed if indicated such as microbiological culture, Gram stain and cytopathology.

The "serum-ascites albumin gradient" (SAAG) is probably a better discriminant than older measures (transudate versus exudate) for the causes of ascites. A high gradient (> 1.1 g/dL) indicates the ascites is due to portal hypertension. A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive as a cause.

Ultrasound investigation is often performed prior to attempts to remove fluid from the abdomen. This may reveal the size and shape of the abdominal organs, and Doppler studies may show the direction of flow in the portal vein, as well as detecting Budd-Chiari syndrome (thrombosis of the hepatic vein) and portal vein thrombosis. Additionally, the sonographer can make an estimation of the amount of ascitic fluid, and difficult-to-drain ascites may be drained under ultrasound guidance. An abdominal CT scan is a more accurate alternate to reveal abdominal organ structure and morphology.

Diagnosis is made by an assessment of symptoms, physical exam, and medical history, in conjunction with blood tests, a liver biopsy, and imaging. Diagnosis is often made following investigation of prolonged jaundice that is resistant to phototherapy and/or exchange transfusions, with abnormalities in liver enzyme tests. Ultrasound or other forms of imaging can confirm the diagnosis. Further testing may include radioactive scans of the liver and a liver biopsy.

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

PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:

- serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months;

- cholangiography demonstrating biliary strictures or irregularity consistent with PSC; and,

- liver biopsy consistent with PSC (if available).

Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its non-invasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.

Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies; however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).

Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.

The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation non-anastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, response to treatment, and risks of disease progression.