Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

early disease

1st line – observation and lifestyle change

Back
ACUTE
|
early disease
1st line – 

observation and lifestyle change

Asymptomatic patients only require observation, general lifestyle changes (including maintaining a healthy diet and weight, and limiting alcohol use), and 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.

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][55] 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 noninvasive screening for IBD via measurement of fecal calprotectin levels, with endoscopic assessment reserved for those with raised fecal calprotectin levels or symptoms.[2]

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.[3]

Consider – pruritus relief

Back
ACUTE
|
early disease
Consider – 

pruritus relief

Treatment recommended for SOME patients in selected patient group

Based primarily on clinical experience, bile acid sequestrants (e.g., cholestyramine) have been considered first-line agents for the relief of itching for many years and are effective.[3][56] However, interference with absorption of other medications and constipation limit their use and indicate the use of alternative agents.[3][57][58][59]

Alternative agents include rifampin, naltrexone, and selective serotonin-reuptake inhibitors.[3][57][58][59] Phenobarbital, phototherapy, or plasmapheresis can be used in patients who do not respond to rifampin, naltrexone, and selective serotonin-reuptake inhibitors.[3]

Primary options

cholestyramine: children >6 years of age: 80 mg/kg orally three times daily; adults: 4-16 g/day orally given in 2 divided doses

Secondary options

rifampin: children and adults: 10 mg/kg orally once daily, maximum 600 mg/day

OR

naltrexone: children: consult specialist for guidance on dose; adults: 25-50 mg orally once daily

OR

sertraline: children: consult specialist for guidance on dose; adults: 75-100 mg orally once daily

Tertiary options

phenobarbital: children and adults: consult specialist for guidance on dose

Consider – ursodiol (ursodeoxycholic acid)

Back
ACUTE
|
early disease
Consider – 

ursodiol (ursodeoxycholic acid)

Treatment recommended for SOME patients in selected patient group

Ursodiol is licensed in some countries for use in patients with PSC.

American Association for the Study of Liver Diseases practice guidance states that ursodiol 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 normalization of alkaline phosphatase (adults) or gamma‐glutamyltransferase (children) in that time.[3]

European guidelines do not make firm recommendations, but state that ursodiol can be given to patients with PSC as it may improve serum liver tests and surrogate markers of prognosis.[2]

Primary options

ursodiol: 13-15 mg/kg/day orally given in 2-4 divided doses

More

Consider – immunosuppressants

Back
ACUTE
|
early disease
|
with overlapping autoimmune hepatitis
Consider – 

immunosuppressants

Treatment recommended for SOME patients in selected patient group

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][62] See Autoimmune hepatitis.

Plus – interventional procedure

Back
ACUTE
|
early disease
|
with symptomatic dominant/relevant stricture
Plus – 

interventional procedure

Treatment recommended for ALL patients in selected patient group

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 endoscopic retrograde cholangiopancreatography (ERCP), and balloon dilation of the stricture. This can improve cholestasis, pruritus, and possibly survival rates.[63][64][65] 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][66][67] 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.[68]

Endoscopic removal of primary bile duct stones (due to bile stasis above strictures) may also lead to clinical improvement.[63] 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.[48][63][69][70]

If endoscopic access to the biliary tree is unsuccessful, percutaneous transhepatic cholangiography 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 noncirrhotic patients in whom endoscopic therapy is ineffective.[71]

end-stage liver disease

1st line – liver transplantation

Back
ACUTE
|
end-stage liver disease
1st line – 

liver transplantation

Liver transplantation is the only therapeutic option for patients with end-stage liver disease due to PSC. It 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 prioritize patients with PSC for liver transplantation. Liver transplantation provides excellent long-term results with 10-year patient survival of 70%.[72] Recurrence of PSC in the graft does occur in 10% to 20% of patients and can lead to graft failure requiring retransplantation.[73][74][75][76]

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer