Approach

Management involves treating symptoms and associated complications, and liver transplantation for end-stage liver disease. Options discussed here are generally based on the American Association for the Study of Liver Diseases (AASLD) guidelines.[3] However, recommendations may differ in other countries. To enhance the possibility of successful drug development, US guidance recommends that all patients with PSC be considered for participation in clinical trials.

Early disease

Patients with early disease may be asymptomatic, requiring observation, general lifestyle measures, and monitoring for complications of PSC.

Recommendations for all patients with chronic liver disease include maintaining a healthy diet and weight (to avoid potential liver damage from metabolic dysfunction-associated steatotic liver disease [formerly known as non-alcoholic fatty liver disease]) and limiting alcohol use (to avoid alcohol-related liver damage). These recommendations, however, are not evidence based.

Relief of pruritus symptoms

Patients commonly experience significant pruritus, which results in poor quality of life. Dominant or relevant strictures or obstruction should be ruled out by magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) in patients with PSC and new-onset pruritus, with any strictures managed by endoscopic retrograde cholangiopancreatography (ERCP). If no relevant strictures are present, treatment should start with heat avoidance, emollients, and antihistamines.[3] If these measures are ineffective, patients can be treated using pharmacotherapy.

Based primarily on clinical experience, bile acid sequestrants have been considered first-line agents for the relief of itching for many years and are effective.[3][54] However, interference with absorption of other medications and constipation limit their use. Alternative agents include rifampicin, naltrexone, and selective serotonin-reuptake inhibitors.[3][55][56][57] Phenobarbital, phototherapy, or plasmapheresis can be used in patients who do not respond to rifampicin, naltrexone, and selective serotonin-reuptake inhibitors.[3] These options are based on the AASLD guidelines.[3] However, recommendations may differ in other countries. For example, bezafibrate is the recommended first-line option in European guidelines (see Emerging treatments). European guidelines support the use of rifampicin and naltrexone but not colestyramine, sertraline, or phenobarbital. Consult your local guidelines for options.[2]

Use of immunosuppressants

Immunosuppressant agents do not improve outcomes in patients with PSC and are not recommended.[30][34][58][59] Corticosteroids and biological agents are also not suggested for routine treatment of PSC.[2] Concomitant autoimmune hepatitis in patients with PSC-autoimmune hepatitis overlap syndrome can, however, be managed with immunosuppressive therapy, and corticosteroids may also be considered.[2][30][60] See Autoimmune hepatitis (Management approach).

Monitoring for complications

Bone mineral density scanning is suggested in all patients at diagnosis and at 2- to 3- or 4-year intervals (based on risk factors) to exclude osteoporosis.[2][30][34][38][39] Patients diagnosed with osteoporosis should receive appropriate treatment. See Osteoporosis.

Adult patients newly diagnosed with PSC should undergo ileocolonoscopy with biopsies regardless of whether or not they already have a diagnosis of inflammatory bowel disease (IBD). Ileocolonoscopy should be repeated (US guidance) or considered (European guidelines) every 5 years if IBD is not present or whenever the patient has symptoms suggestive of IBD.[2][3] From the age of 15 years, all patients with co-existing IBD should undergo surveillance colonoscopy regularly due to a high risk of colorectal cancer.[30][34][61] US guidance suggests 1- to 2-year surveillance intervals, whereas European guidelines recommend surveillance annually, with 1- to 2-year intervals if there is no inflammatory activity.[2][3][30][34][40] Children with PSC can undergo initial non-invasive screening for IBD via measurement of faecal calprotectin levels, with endoscopic assessment reserved for those with raised faecal calprotectin levels or symptoms.[2] Treatment of PSC-related IBD should follow current practice guidelines for IBD in striving for mucosal healing. See Crohn's disease and Ulcerative colitis.

Dominant/relevant stricture

Patients with dominant/relevant strictures (strictures of the extrahepatic biliary tree) who are acutely ill (rapidly worsening jaundice and pruritus, acute bacterial cholangitis, deteriorating liver function tests) require ERCP and balloon dilation of the stricture. This can improve cholestasis, pruritus, and survival rates.[62][63][64] Placement of a removable plastic stent across the stricture has been associated with increased complications, and placement is left to the discretion of the endoscopist.[3][65][66] If a stent is placed, it should generally be removed within 4 weeks.[3] Common adverse events associated with endoscopic dilation and stent placement are associated bleeding and perforation; stents are also associated with migration, occlusion, and aspiration pneumonia.[67]

Endoscopic removal of primary bile duct stones (due to bile stasis above strictures) may also lead to clinical improvement.[62] Patients with diffuse intrahepatic biliary stricturing, but no focal extrahepatic biliary stricture, are less likely to derive benefit from endoscopic treatment. Prophylactic antibiotics prior to the procedure are recommended as ERCP in patients with PSC is associated with about 10% risk of complications (including pancreatitis, cholangitis, sepsis, liver abscess, bleeding, and perforation).[3][48][62][68][69]

If endoscopic access to the biliary tree is unsuccessful, percutaneous transhepatic cholangiography (PTC) can facilitate biliary drainage, stent placement, and/or stricture dilation. Brush cytology should be performed to rule out cholangiocarcinoma, although yields are notably as low as 18%.[45] Surgical therapy for dominant strictures can be considered in carefully selected non-cirrhotic patients in whom endoscopic therapy is ineffective.[70]

End-stage liver disease

Most patients will develop complications of end-stage liver disease, including oesophageal varices and ascites. Management of these complications is similar to that for advanced chronic liver disease from other causes. Portal hypertension can also develop in patients with PSC due to progressive hepatic fibrosis and cirrhosis, and the complications of portal hypertension in PSC should be managed according to local guidelines.[2] Patients with advanced liver disease or cirrhosis should be referred to a liver transplantation centre for evaluation and management.

Liver transplantation is the only therapeutic option for patients with end-stage liver disease due to PSC. Liver transplantation is indicated when expected survival after transplantation exceeds that predicted without transplantation. The unpredictable natural history of PSC, including the development of cholangiocarcinoma, makes determining the optimal timing of liver transplantation a challenge, but European guidelines recommend it be considered once patients have decompensated cirrhosis.[2] Similar to other causes of end-stage liver disease, the MELD score is used to prioritise patients with PSC for liver transplantation. [ MELDNa scores (for liver transplantation listing purposes, not appropriate for patients under age 12 years) (SI units) Opens in new window ] Liver transplantation provides excellent long-term results with 10-year patient survival of 70%.[71] Recurrence of PSC in the graft does occur in 10% to 20% of patients and can lead to graft failure requiring re-transplantation.[72][73][74][75]

European guidelines recommend liver transplantation for PSC be performed using a duct-to-duct anastomosis unless a Roux-en-Y hepaticojejunostomy is warranted.[2]

Ursodeoxycholic acid

Ursodeoxycholic acid is a hydrophilic bile acid that replaces the more common hydrophobic bile acids (thought to be hepatotoxic in the setting of cholestasis).

Historically, evidence for the efficacy of ursodeoxycholic acid in PSC has been inconsistent, and previous recommendations advised against using it as a treatment.[30] Findings have been inconclusive for low- and medium-dose ursodeoxycholic acid, hampered by underpowered studies, and unfavourable for high-dose ursodeoxycholic acid, owing to an increased risk of serious adverse events and, for patients with ulcerative colitis PSC, an increased risk of colorectal neoplasia.[76][77] [ Cochrane Clinical Answers logo ] More recently, significantly better outcomes have been reported in patients who experience meaningful reductions or normalisation of alkaline phosphatase (adults) or gamma‐glutamyltransferase (children).[78][79][80][81][82] In addition, worsening of fatigue, pruritus, liver biochemistries, and the Mayo PSC Risk score have been associated with withdrawal of ursodeoxycholic acid.[83][84]

Ursodeoxycholic acid is licensed in some countries for use in patients with PSC. European guidelines do not make firm recommendations, but state that ursodeoxycholic acid can be given to patients with PSC as it may improve serum liver tests and surrogate markers of prognosis.[2] AASLD practice guidance states that ursodeoxycholic acid can be considered for patients with PSC who have persistently elevated levels of alkaline phosphatase or gamma‐glutamyltransferase if they are not interested in, or eligible for, clinical trials, and that it may be continued beyond 12 months if symptoms have improved and/or there has been a meaningful reduction or normalisation of alkaline phosphatase (adults) or gamma‐glutamyltransferase (children) in that time.[3]

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