Although there is no curative treatment, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody against the pro-fibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC.

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.

The clinical course of biliary sludge can do one of three things: (1) it can resolve completely, (2) wax and wane, or (3) progress to gallstones. If the biliary sludge has a cause (e.g. pregnancy), it oftentimes is resolved when the underlying cause is removed.

Extrahepatic cholestasis can usually be treated by surgery.

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

Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.

For patients without symptoms, no treatment is recommended. If patients become symptomatic and/or develop complications, cholecystectomy is indicated. For those who are poor surgical candidates, endoscopic sphincterotomy may be performed to reduce the risk of developing pancreatitis.

SSC is thought to develop as a consequence of known injuries or pathological processes of the biliary tree, such as biliary obstruction, surgical trauma to the bile duct, or ischemic injury to the biliary tree. Secondary causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. It has been clearly demonstrated sclerosing cholangitis can develop after an episode of severe bacterial cholangitis. Also it was suggested that it can result from insult to the biliary tree by obstructive cholangitis secondary to choledocholithiasis, surgical damage, trauma, vascular insults, parasites, or congenital fibrocystic disorders. Additional causes of secondary SC are toxic, due to chemical agents or drugs.

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.

Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system). Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm "Ascaris lumbricoides" and the liver flukes "Clonorchis sinensis", "Opisthorchis viverrini" and "Opisthorchis felineus". In people with AIDS, a large number of opportunistic organisms has been known to cause "AIDS cholangiopathy", but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.

The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.

Gallstone risk increases for females (especially before menopause) and for people near or above 40 years; the condition is more prevalent among both North and South Americans and among those of European descent than among other ethnicities. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder. Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and low calorie diet. The absence of such risk factors does not, however, preclude the formation of gallstones.

Nutritional factors that may increase risk of gallstones include constipation; eating fewer meals per day; low intake of the nutrients folate, magnesium, calcium, and vitamin C; low fluid consumption; and, at least for men, a high intake of carbohydrate, a high glycemic load, and high glycemic index diet. Wine and whole-grained bread may decrease the risk of gallstones.

Rapid weight loss increases risk of gallstones. Patients taking orlistat, a weight loss drug, may already be at increased risk for the formation of gallstones. Weight loss with orlistat can increase the risk of gallstones. On the contrary, ursodeoxycholic acid (UDCA), a bile acid, also a drug marketed as Ursodiol, appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones.

Cholecystokinin deficiency caused by celiac disease increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed.

Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as from sickle-cell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections. People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones. Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.

Cholesterol modifying medications can affect gallstone formation. Statins inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones. Fibrates increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones.

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.

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic liver disease. It is an aggressive and rare disease with complex and multiple causes. It is characterized by inflammation, fibrosis, destruction of the biliary tree and biliary cirrhosis. It can be treated with minor interventions, antibiotics, and monitoring, or with more serious cases, surgery, endoscopic intervention, and liver transplantation.

Initial management includes the relief of symptoms and correcting electrolyte and fluid imbalance that may occur with vomiting. Antiemetics, such as dimenhydrinate, are used to treat the nausea. Pain may be treated with anti-inflammatories, NSAIDs such as ketorolac or diclofenac. Opioids, such as morphine, less commonly may be used. NSAIDs are more or less equivalent to opioids. Hyoscine butylbromide, an antispasmodic, is also indicated in biliary colic.

In biliary colic, the risk of infection is minimal and therefore antibiotics are not required. Presence of infection indicates cholecystitis.

Recurrent pyogenic cholangitis is characterised by recurrent bouts of bacterial cholangitis with primary hepatolithiasis. It is prevalent in Hong Kong and East Asian including China, Taiwan, Korea, Japan, Indonesia and the Philippines. Apart from affecting humans it is also a common disease in cats.

In RPC the gallstones found within the biliary system are calcium bilirubinate stones or pigmented calcium stones. Calcium bilirubinate stones are prevalent in Asia and very rare in Europe and the United States. In addition to the presence of these friable concretions of various shapes and sizes within the biliary tree, the bile is often muddy in consistency and contains numerous fine particles of calcium bilirubinate. This differs greatly from cholesterol stones, which are common in Europe and the United States. Pure cholesterol stones contain >96% cholesterol whereas mixed cholesterol stones contain 71.3% cholesterol. The formation of calcium bilirubinate stones in RPC has been attributed to the high incidence of infection with "Escherichia coli" in the bile. In humans, the majority of bilirubin is excreted in the bile as bilirubin glucuronide.

Hepatolithiasis is associated with Clonorchis sinensis and Ascaris lumbricoides infestation of the liver. This theory is based on high incidence of dead parasites or ova within stone in autopsy findings.

Many herbal and antioxidant remedies have been advocated for chronic liver disease but the evidence is not conclusive. Some support may be found in the orthodox medical use of two of these: N-acetyl cysteine (NAC), is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle (Silybum marianum) or its derivative silibinin are used in liver poisoning from certain mushrooms, notably amanita phalloides, although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang, chaparral, comfrey, germander, greater celandine, kava, mistletoe, pennyroyal, skull cap and valerian.

Treatment involves an operation called a choledocholithotomy, which is the removal of the gallstone from the bile duct using ERCP, although surgeons are now increasingly using laparoscopy with cholangiography. In this procedure, tiny incisions are made in the abdomen and then in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiography. If stones are identified, the surgeon inserts a tube with an inflatable balloon to widen the duct and the stones are usually removed using either a balloon or tiny basket.

If laparoscopy is unsuccessful, an open choledocholithotomy is performed. This procedure may be used in the case of large stones, when the duct anatomy is complex, during or after some gallbladder operations when stones are detected, or when ERCP or laparoscopic procedures are not available.

Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.

AIP often completely resolves with steroid treatment. The failure to differentiate AIP from malignancy may lead to unnecessary pancreatic resection, and the characteristic lymphoplasmacytic infiltrate of AIP has been found in up to 23% of patients undergoing pancreatic resection for suspected malignancy who are ultimately found to have benign disease. In this subset of patients, a trial of steroid therapy may have prevented a Whipple procedure or complete pancreatectomy for a benign disease which responds well to medical therapy. "This benign disease resembles pancreatic carcinoma both clinically and radiographically. The diagnosis of autoimmune pancreatitis is challenging to make. However, accurate and timely diagnosis may preempt the misdiagnosis of cancer and decrease the number of unnecessary pancreatic resections." Autoimmune pancreatitis responds dramatically to corticosteroid treatment.

If relapse occurs after corticosteroid treatment or corticosteroid treatment is not tolerated, immunomodulators may be used. Immunomodulators such as azathioprine, and 6-mercaptopurine have been shown to extend remission of autoimmune pancreatitis after corticosteroid treatment. If corticosteroid and immunomodulator treatments are not sufficient, rituximab may also be used. Rituximab has been shown to induce and maintain remission.

Gallstones are a valuable by-product of animals butchered for meat because their use as a purported antipyretic and antidote in the folk remedies of some cultures, in particular, in China. The finest gallstones tend to be sourced from old dairy cows, termed calculus bovis or "niu-huang" (yellow thing of cattle) in Chinese. Much as in the manner of diamond mines, slaughterhouses carefully scrutinize workers for gallstone theft.

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.

It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not. The scientific basis to assess whether surgery outperformed other treatment was insufficient and better studies were needed as of a SBU report in 2017. Treatment of biliary colic is dictated by the underlying cause. The presence of gallstones, usually visualized by ultrasound, generally necessitates a surgical treatment (removal of the gall bladder, typically via laparoscopy). Removal of the gallbladder with surgery, known as a cholecystectomy, is the definitive surgical treatment for biliary colic. A 2013 Cochrane review found tentative evidence to suggest that early gallbladder removal may be better than delayed removal. Early laparoscopic cholescystectomy happens within 72 hours of diagnosis. In a Cochrane review that evaluated receiving early versus delayed surgery, they found that 23% of those who waited on average 4 months ended up in hospital for complications, compared to none with early intervention with surgery. Early intervention has other advantages including reduced number of visits to the emergency department, less conversions to an open surgery, less operating time required, reduced time in hospital post operatively. The Swedish agency SBU estimated in 2017 that increasing acute phase surgeries could

free multiple in-hospital days per patient and would additionally spare pain and suffering in wait of receiving an operation. The report found that those with acute inflammation of the gallbladder can be surgically treated in the acute phase, within a few days of symptom debut, without increasing the risk for complications (compared to when the surgery is done later in an asymptomatic stage).

As the number of published cases of AIP has increased, efforts have been focused on defining AIP as a distinct clinical and pathologic entity and toward developing some generally agreed upon diagnostic criteria and nomenclature. Terms frequently encountered are autoimmune or autoimmune-related pancreatitis, lymphoplasmacytic sclerosing pancreatitis, idiopathic tumefactive chronic pancreatitis, idiopathic pancreatitis with focal irregular narrowing of the main pancreatic duct, and non-alcoholic duct destructive chronic pancreatitis. There are also a large number of case reports employing descriptive terminology such as pancreatitis associated with Sjögren’s syndrome, primary sclerosing cholangitis, or inflammatory bowel disease. Some of the earliest cases were reported as pancreatic pseudotumor or pseudolymphoma.

Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (thus "" + ""). This condition causes jaundice and liver cell damage. Treatment is by cholecystectomy and ERCP.

The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including corticosteroids, interferon, antivirals, bile acids or other drugs. Supportive therapy for complications of cirrhosis include diuretics, albumin, vitamin K, blood products, antibiotics and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.

Cholestasis means "the slowing or stopping of bile flow" which can be caused by any number of diseases of the liver (which produces the bile), the gallbladder (which stores the bile), or biliary tract (also known as the biliary tree, the conduit that allows the bile to leave the liver and gallbladder and enter the small intestine). When this occurs, conjugated bilirubin and the waste products that usually would be cleared in bile reflux back into the bloodstream. This causes a primarily conjugated hyperbilirubinemia and jaundice; the liver conjugates the bile to make it water-soluble and because the bile has already been processed by the liver, when it gets backed up because of a blockage and is refluxed into the blood, the blood will have high levels of conjugated bilirubin. This is in contrast to primarily unconjugated hyperbilirubinemia which is the water-insoluble form that is bound to serum albumin; the liver has not had a chance to conjugate the bilirubin yet and can be caused either because too much unconjugated bilirubin is made (such as in massive hemolysis or ineffective erythropoiesis) or because too little is conjugated (Gilbert's disease or Crigler-Najjar syndrome). Unconjugated hyperbilirubinemia does not typically cause pruritus.

It is thought that bile salts that deposit into the skin are responsible for the pruritus (itching) but the levels of bilirubin in the bloodstream and the severity of the pruritus does not appear to be highly correlated. Patients that have been administered bile salt chelating agents do report some relief, however, and patients that have complete liver cell failure (and therefore cannot make these products to begin with) do not have pruritus. This suggests that products made by the liver must have some role in pruritus although it is not known exactly which product is responsible.