Initial treatment is supportive, with the use of agents to treat cholestasis and pruritus, including the following:

- Ursodeoxycholic acid

- Cholestyramine

- Rifampin

- Naloxone, in refractory cases

The partial external biliary diversion (PEBD) procedure is a surgical approach that diverts bile from the gallbladder externally into an ileostomy bag.

Patients should be supplemented with fat-soluble vitamins, and occasionally medium-chain triglycerides in order to improve growth.

When liver synthetic dysfunction is significant, patients should be listed for transplantation. Family members should be tested for PFIC mutations, in order to determine risk of transmission.

Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal lifespans. Some neonates present with cholestasis. Hormonal contraceptives and pregnancy may lead to overt jaundice and icterus (yellowing of the eyes and skin).

Typically no treatment is needed. If jaundice is significant phenobarbital may be used.

There are multiple treatment methods. Low protein diets, are intended to minimize production of ammonia. Arginine, sodium benzoate and sodium phenylacetate help to remove ammonia from the blood. Dialysis may be used to remove ammonia from the blood when it reaches critical levels.

In some cases, liver transplant has been successful.

There is no known cure, but medication may slow the progression so that a normal lifespan and quality of life may be attainable for many patients.

- Ursodeoxycholic acid (Ursodiol) is the most frequently used treatment. It helps reduce the cholestasis and improves liver function tests. It has a minimal effect on symptoms and whether it improves outcomes is controversial. A Cochrane review from 2012 did not show any significant benefits on important outcomes including mortality, liver transplantation or PBC symptoms, even if some biochemistry and histological parameters were improved.

- To relieve itching caused by bile acids in circulation, which are normally removed by the liver, cholestyramine (a bile acid sequestrant) may be prescribed to absorb bile acids in the gut and be eliminated, rather than re-enter the blood stream. Other drugs that do this include stanozolol, naltrexone and rifampicin.

- Specific treatment for fatigue, which may be debilitating in some patients, is limited and undergoing trials. Some studies indicate that Provigil (modafinil) may be effective without damaging the liver. Though modafinil is no longer covered by patents, the limiting factor in its use in the U.S. is cost. The manufacturer, Cephalon, has made agreements with manufacturers of generic modafinil to provide payments in exchange for delaying their sale of modafinil. The FTC has filed suit against Cephalon alleging anti-competitive behavior.

- People with PBC may have poor lipid-dependent absorption of Vitamins A, D, E, K. Appropriate supplementation is recommended when bilirubin is elevated.

- People with PBC are at elevated risk of developing osteoporosis and esophageal varices as compared to the general population and others with liver disease. Screening and treatment of these complications is an important part of the management of PBC.

- As in all liver diseases, consumption of alcohol is contraindicated.

- In advanced cases, a liver transplant, if successful, results in a favorable prognosis.

- The farnesoid X receptor agonist, obeticholic acid, which is a modified bile acid, was approved by the United States Food and Drug Administration on May 27, 2016, as an orphan drug in an accelerated approval program, based on its reduction in the level of the biomarker alkaline phosphatase, as a surrogate endpoint for clinical benefit. It is indicated for the treatment of PBC in combination with ursodeoxycholic acid in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Additional studies are being required to prove its clinical benefit.

Surgical treatment is best, when it can be performed. Pressure within the portal vein is measured as the shunt is closed, and it must be kept below 20 cm HO or else portal hypertension will ensue. Methods of shunt attenuation should aim to slowly occlude the vessel over several weeks to months in order to avoid complications associated with portal hypertension. These methods include ameroid ring constrictors, cellophane banding, intravascular or percutaneous silicone hydraulic occluders. The most common methods of attenuation used by veterinarians are ameroid ring constrictors and cellophane banding. Both methods have reportedly good outcomes in both cats and dogs, although the true composition of readily sourced cellophane has been found to be made from plastics (inert) and not cellulose (stimulates a fibrous reaction). Recently, a commercial supplier of regenerated cellulose based cellophane for veterinarians has been established for use of cellophane banding for portosystemic shunts in dogs and cats. Complete closure of extrahepatic shunts results in a very low recurrence rate, while incomplete closure results in a recurrence rate of about 50 percent. However, not all dogs with extrahepatic shunts tolerate complete closure (16 to 68 percent). Intrahepatic shunts are much more difficult to surgically correct than extrahepatic shunts due to their hidden nature, large vessel size, and greater tendency toward portal hypertension when completely closed. When surgery is not an option, PSS is treated as are other forms of liver failure. Dietary protein restriction is helpful to lessen signs of hepatic encephalopathy, and antibiotics such as neomycin or metronidazole and other medicines such as lactulose can reduce ammonia production and absorption in the intestines. The prognosis is guarded for any form of PSS.

The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.

Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. Ursodiol is given to treat cholelithiasis. In diffuse cases of Caroli disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures, and liver transplantation in carefully selected cases. Surgical resection has been used successfully in patients with monolobar disease. An orthotopic liver transplant is another option, used only when antibiotics have no effect, in combination with recurring cholangitis. With a liver transplant, cholangiocarcinoma is usually avoided in the long run.

Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed.

Most (>95%) infants with biliary atresia will undergo an operation designed to retain and salvage the native liver, restore bile flow and reduce the level of jaundice. This is known as the Kasai procedure (after Morio Kasai, the Japanese surgeon who first developed the technique) or hepatoportoenterostomy. Although the procedure is not thought of as curative, it may relieve jaundice, and stop liver fibrosis allowing normal growth and development. Published series from Japan, North America and the UK show that bilirubin levels will fall to normal values in about 50-55% of infants allowing 40-50% to retain their own liver to reach the age of 5 and 10 years (and beyond). Liver transplantation is an option for those children whose liver function and symptoms fail to respond to a Kasai operation.

Recent large-scale studies by Davenport et al. ("Annals of Surgery", 2008) show that the age of the patient is not an absolute clinical factor affecting prognosis. The influence of age differs according to the disease etiology—i.e., whether biliary atresia is isolated, cystic (CBA), or accompanied by splenic malformation (BASM).

It is widely accepted that corticosteroid treatment after a Kasai operation, with or without choleretics and antibiotics, has a beneficial effect on postoperative bile flow and can clear jaundice, but the dosing and duration of the ideal steroid protocol are controversial. Furthermore, it has been observed in many retrospective longitudinal studies that corticosteroid treatment does not prolong survival of the native liver or transplant-free survival. Davenport et al. also showed ("Hepatology" 2007) that short-term, low-dose steroid therapy following a Kasai operation had no effect on the mid- or long-term prognosis of biliary atresia patients.

A minority of patients can be treated medically with sodium restriction, diuretics to control ascites, anticoagulants such as heparin and warfarin, and general symptomatic management. The majority of patients require further intervention. Milder forms of Budd–Chiari may be treated with surgical shunts to divert blood flow around the obstruction or the liver itself. Shunts must be placed early after diagnosis for best results. The TIPS is similar to a surgical shunt: it accomplishes the same goal but has a lower procedure-related mortality—a factor that has led to a growth in its popularity. If all the hepatic veins are blocked, the portal vein can be approached via the intrahepatic part of inferior vena cava, a procedure called DIPS (direct intrahepatic portocaval shunt). Patients with stenosis or vena caval obstruction may benefit from angioplasty. Limited studies on thrombolysis with direct infusion of urokinase and tissue plasminogen activator into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted.

Liver transplantation is an effective treatment for Budd–Chiari. It is generally reserved for patients with fulminant liver failure, failure of shunts or progression of cirrhosis that reduces the life expectancy to 1 year. Long-term survival after transplantation ranges from 69–87%. The most common complications of transplant include rejection, arterial or venous thromboses and bleeding due to anticoagulation. Up to 10% of patients may have a recurrence of Budd–Chiari syndrome after the transplant.

Extrahepatic cholestasis can usually be treated by surgery.

Pruritis in cholestatic jaundice is treated by Antihistamines, Ursodeoxycholic Acid, Phenobarbital

No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.

Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as (cholestyramine)); antibiotics to treat episodes of acute cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K).

ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile duct cancer (cholangiocarcinoma).

Liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will need it. Indications for transplantation include recurrent bacterial cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some will experience disease recurrence afterward.

Often, aggressive treatment is unnecessary for people with MSK disease that does not cause any symptoms (asymptomatic). In such cases, treatment may consist of maintaining adequate fluid intake, with the goal of decreasing the risk of developing kidney stones (nephrolithiasis). Cases of recurrent kidney stone formation may warrant evaluation for possible underlying metabolic abnormalities.

In patients with low levels of citrate in the urine (hypocitraturia) and incomplete distal renal tubular acidosis, treatment with potassium citrate helps prevent the formation of new kidney stones. Urinary tract infections, when they occur, should also be treated.

Patients with the more rare form of MSK marked by chronic pain typically require pain management. Non-obstructing stones in MSK can be associated with significant and chronic pain even if they're not passing. The pain in this situation can be constant. It is not certain what causes this pain but researchers have proposed that the small numerous stones seen in MSK may cause obstruction of the small tubules and collecting ducts in the kidney which could lead to the pain. This pain can often be debilitating and treatment is challenging. Narcotic medication even with large quantities is sometimes not adequate. Some success with pain control has been reported using laser lithotripsy (called “ureteroscopic laser papillotomy”).

Neonatal seizures are often controlled with phenobarbital administration. Recurrent seizures later in life are treated in the standard ways (covered in the main epilepsy article). Depending on the severity, some infants are sent home with heart and oxygen monitors that are hooked to the child with stick on electrodes to signal any seizure activity. Once a month the monitor readings are downloaded into a central location for the doctor to be able to read at a future date. This monitor is only kept as a safeguard as usually the medication wards off any seizures. Once the child is weaned off the phenobarbital, the monitor is no longer necessary.

The disease is typically progressive, leading to fulminant liver failure and death in childhood, in the absence of liver transplantation. Hepatocellular carcinoma may develop in PFIC-2 at a very early age; even toddlers have been affected.

Clinical practice guidelines by the American College of Gastroenterology have recommended corticosteroid treatment. Patients should be risk stratified using a MELD Score or Child-Pugh score.

- Corticosteroids: These guidelines suggest that patients with a modified Maddrey's discriminant function score > 32 or hepatic encephalopathy should be considered for treatment with prednisolone 40 mg daily for four weeks followed by a taper. Models such as the Lille Model can be used to monitor for improvement or to consider alternative treatment.

- Pentoxifylline: A randomized controlled trial found that among patients with a discriminant function score > 32 and at least one of the following symptoms (a palpable, tender enlarged liver, fever, high white blood cell count, hepatic encephalopathy, or hepatic systolic bruit), 4.6 patients must be treated with pentoxifylline for 4 weeks to prevent one patient from dying. Subsequent trials have suggested that pentoxifylline may be superior to prednisolone in the management of acute alcoholic hepatitis with discriminant function score >32. Advantage of pentoxifylline over prednisolone was better tolerability, lesser side effects, with decreased occurrence of renal dysfunction in patients receiving pentoxifylline.

- Potential for combined therapy: A large prospective study of over 1000 patients investigated whether prednisolone and pentoxifylline produced benefits when used alone or in combination. Pentoxifylline did not improve survival alone or in combination. Prednisolone gave a small reduction in mortality at 28 days but this did not reach significance, and there were no improvements in outcomes at 90 days or 1 year.

Treatment for Nasopharyngeal angiofibroma (JNA) is primarily surgical. The tumor is primarily excised by external or endoscopic approach. Medical treatment and radiation therapy are only of historical interest.

External approaches:

- transpalatine approach

- transpalatine + sublabial (Sardana's) Approach

- infratemporal Approach

- nasal endoscopic Approach

- transmaxillary Approach

Endoscopic approach is an excellent tool in primary and recurrent JNA, it allows visualisation and precise removal of the lesion. Preoperative embolisation of tumour may be of some use in reducing intraoperative bleeding.

Direct visualization is not common.

Attacks are self-limiting, and require analgesia and NSAIDs (such as diclofenac). Colchicine, a drug otherwise mainly used in gout, decreases attack frequency in FMF patients. The exact way in which colchicine suppresses attacks is unclear. While this agent is not without side effects (such as abdominal pain and muscle pains), it may markedly improve quality of life in patients. The dosage is typically 1–2 mg a day. Development of amyloidosis is delayed with colchicine treatment. Interferon is being studied as a therapeutic modality. Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.

Approximately 5–10% of FMF cases are resistant to colchicine therapy alone. In these cases, adding anakinra to the daily colchicine regimen has been successful.

Dubin–Johnson syndrome (DJS) is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.

No known treatment for BPT currently exists. However, the condition it is self-limiting and resolves after about eighteen months.

Prurigo nodularis is very hard to treat, but current therapies include steroids, vitamins, cryosurgery, thalidomide and UVB light. In the event that staphylococcus or other infection is present, antibiotics have proven effective, but tend to cause more harm than good for this particular disease.

A physician may administer a strong dose of prednisone, which will almost immediately stop the itch/scratch cycle. However, cessation of steroids allows relapse to occur, usually within a few weeks. Horiuchi "et al" recently reported significant improvement in PN with antibiotic therapy.

Another drug a physician may administer is Apo-Azathioprine. Azathioprine, also known by its brand name Imuran, is an immunosuppressive drug used in organ transplantation and autoimmune diseases and belongs to the chemical class of purine analogues.

The Aagenæs syndrome or Aagenaes syndrome is a syndrome characterised by congenital hypoplasia of lymph vessels, which causes lymphedema of the legs and recurrent cholestasis in infancy, and slow progress to hepatic cirrhosis and giant cell hepatitis with fibrosis of the portal tracts.

The genetic cause is unknown, but it is autosomal recessively inherited and the gene is located to chromosome 15q. A common feature of the condition is a generalised lymphatic anomaly, which may be indicative of the defect being lymphangiogenetic in origin. The condition is particularly frequent in southern Norway, where more than half the cases are reported from, but is found in patients in other parts of Europe and the United States. It is named after Øystein Aagenæs, a Norwegian paediatrician.

It is also called cholestasis-lymphedema syndrome (CLS).

Acute fatty liver of pregnancy is best treated in a centre with expertise in hepatology, high-risk obstetrics, maternal-fetal medicine and neonatology. The physicians who treat this condition will often consult with experts in liver transplantation in severe cases. Admission to the intensive care unit is recommended.

Initial treatment involves supportive management with intravenous fluids, intravenous glucose and blood products, including fresh frozen plasma and cryoprecipitate to correct DIC. The foetus should be monitored with cardiotocography. After the mother is stabilized, arrangements are usually made for delivery. This may occur vaginally, but, in cases of severe bleeding or compromise of the mother's status, a caesarian section may be needed. Often AFLP is not diagnosed until the mother and baby are in trouble, so it is most likely that an emergency C-section is needed.

The complications of acute fatty liver of pregnancy may require treatment after delivery, especially if pancreatitis occurs. Liver transplantation is rarely required for treatment of the condition, but may be needed for mothers with severe DIC, those with rupture of the liver, or those with severe encephalopathy.

Arthrogryposis–renal dysfunction–cholestasis syndrome (also known as "ARC syndrome") is a cutaneous condition caused by a mutation in the VPS33B gene. Most of the cases have been survived for infancy. Recently, College of Medical Sciences in Nepal reports a case of ARC syndrome in a girl at the age of more than 18 years.

The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease in which case patients are generally treated with palliative chemotherapy, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.

If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally ), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.