Last updated September 15, 2022

Primary Sclerosing Cholangitis and Cholangiocarcinoma

Primary Sclerosing Cholangitis

Diagnosis of PSC

  • In patients with suspected PSC, a 3D MRI/MRCP with T1w and T2w axial images and contrast enhancement should be obtained to evaluate for cholangiographic features of PSC, including intrahepatic and/orextrahepatic strictures alternating with normal or slightly dilated segments.
  • In patients with suspected PSC and a normal, high-quality MRI/MRCP, liver biopsy should be considered to rule out small-duct PSC. Patients with an equivocal MRI/MRCP should be referred to an experienced center for consideration of a repeat high-quality MRI/MRCP or liver biopsy. A repeat MRI/MRCP may be considered in 1 year if the diagnosis remains unclear.
  • ERCP should be avoided for the diagnosis of PSC.
  • In all patients with possible PSC, serum IgG4 levels should be measured to exclude IgG4-sclerosing cholangitis.
  • A liver biopsy should not be performed in patients with typical cholangiographic findings on MRI/MRCP, except when there is concern for autoimmune hepatitis overlap.
  • Ileocolonoscopy with biopsies should be performed in patients with a new diagnosis of PSC and no previous diagnosis of IBD. In patients without IBD, subsequent ileocolonoscopy should be considered at 5-year intervals or whenever symptoms suggestive of IBD occur.
  • Patients with small-duct PSC should be monitored by MRI/MRCP every 3–5 years for the development of large-duct disease.
  • Risk stratification and fibrosis staging should be done at diagnosis of PSC and regularly during follow-up. Clinical risk tools can be considered for this purpose, but specific probabilities of events should be interpreted with caution in the individual patient.
  • Liver stiffness measurement by transient elastography or magnetic resonance elastographyis currently the preferred method for estimation of fibrosis stage in PSC.
  • Liver biopsy is not recommended for fibrosis staging in clinical practice.

Management of PSC

  • All patients with PSC should be considered for participation in clinical trials.
  • In patients not eligible or interested in clinical trials with persistently elevated alkaline phosphatase (ALP) or γ-glutamyl transferase (GGT), ursodeoxycholic acid 13–23 mg/kg/day can be considered for treatment 2022and continued if there is a meaningful reduction or normalization in ALP(GGT in children) and/or symptoms improve with 12 months of treatment.
  • Currently, there is insufficient evidence to recommend the use of oral vancomycin for the treatment of PSC.
  • Patients with PSC with a diagnosis of concurrent autoimmune hepatitis should be treated according to the AASLD Autoimmune Hepatitis Guidelines.
  • Antibiotics should be used for bacterial cholangitis with consideration for MRCP to rule out relevant strictures.
  • ERCP should be performed for bacterial cholangitis if there is an inadequate response to antibiotics.
  • Upper endoscopy to screen for varices should be performed if the liver stiffness is >20 kPa by transient elastography or the platelet count is ≤150,000/mm3.

Surveillance for malignancy

  • Cholangiocarcinoma and gallbladder carcinoma surveillance should be performed annually and include abdominal imaging, preferably by MRI/MRCP with or without serum CA 19-9. Surveillance is not recommended for patients with PSC under 18 years of age or with small-duct PSC.
  • Intraductal tissue sampling for cytology and FISH should be performed routinely during ERCP for relevant strictures.
  • Cholecystectomy should be considered for patients with PSC with gallbladder polyps >8 mm, preferably at an experienced center in patients with advanced disease. Polyps ≤8 mm may be monitored with ultrasound every 6 months.
  • Patients with PSC with cirrhosis should undergo HCC surveillanceconsistent with current AASLD Guidelines.

Colon cancer

  • In patients with PSC in whom IBD is diagnosed, high-definition surveillance colonoscopy with biopsies should start at age 15 years and be repeated at 1- to 2-year intervals to evaluate for colonic dysplasia.

Endoscopic and percutaneous therapy

  • ERCP may be indicated for the evaluation of relevant strictures as well as new-onset or worsening pruritus, unexplained weight loss, worsening serum liver test abnormalities, rising serum CA 19-9, recurrent bacterial cholangitis, or progressive bile duct dilation. MRI/MRCP should be considered prior to ERCP to clarify the need for biliary intervention and guide the technical approach.
  • Antimicrobial prophylaxis should be administered during the peri-procedure period in patients with PSC undergoing ERCP.
  • The choice between biliary balloon dilation with or without stenting should be left to the endoscopist’s discretion. In cases where a plastic biliary stent is placed, the stent should generally be removed within 4 weeks following placement.

Nutrition and mineral bone disease in PSC

  • Bile acid sequestrants should be used as initial therapy for patients with PSC who have pruritus that does not respond to conservative measures such as heat avoidance, emollients, and antihistamines. Alternatives for refractory pruritus include sertraline 100 mg daily, naltrexone titrated to a dose of 50–100 mg daily, and rifampin 150–300 mg twice daily.
  • Management of IBD in patients with PSC is similar to those without PSC.Active management of IBD and surveillance of colon cancer should continue in the post-transplant period.
  • Nutritional assessments, including but not limited to biometrics and lipid-soluble vitamin levels, should be performed at PSC diagnosis and yearly thereafter with nutritional intervention and vitamin supplementation as needed.
  • Bone density examinations should be performed to exclude osteopenia or osteoporosis at diagnosis and at 2–3 year intervals thereafter based on risk factors.

Recurrent PSC

  • Liver transplantation should be considered in all patients with PSC and complications of end-stage liver disease, recurrent cholangitis, intractable pruritus, or early-stage hepatobiliary cancers.
  • Patients with elevated liver enzymes after transplant should undergo histological and cholangiographic assessments to distinguish rPSC from allograft rejection and/or biliary complications.

Cholangiocarcinoma

iCCA

Diagnosis

  • An elevated CA 19-9 alone should not be used to diagnose CCA.
  • Histopathological confirmation is required for definitive diagnosis of iCCA.
  • Cross-sectional imaging of the liver such as multiphasic CT or MRI are required to facilitate assessment of the primary mass, vascular invasion, presence of intra- or extrahepatic metastasis, and resectability.
  • Cross-sectional imaging of the chest and abdomen is necessary to stage the disease.
  • PET scan should not be used for diagnosis of primary tumor in CCA.

Surgical  resection

  • Surgical resection is the treatment of choice for patients with a single iCCA nodule in a resectable location without evidence of metastatic disease and who have adequate functional liver volume.
  • Patients diagnosed with iCCA should be referred to a center with surgical expertise in hepatobiliary malignancies.
  • Adjuvant capecitabine should be considered for all patients with CCA.

LT for iCCA

  • Liver transplantation for unresectable liver-limited iCCA should only be considered under research protocols.

LRT

  • Data are insufficient to recommend locoregional therapy as a standard therapy for locally advanced unresectable iCCA.

Perihilar and distal CCA 

Diagnosis

  • Cross-sectional imaging and cholangiographic studies are required in patients with suspected pCCA or dCCA for assessment of tumor extent along the biliary tree, identification of mass lesions, contrast enhancement, and vascular encasement.
  • ERCP with biliary brushings for cytology and FISH analysis should be obtained in patients with suspected pCCA and dCCA.
  • For pCCA, EUS-guided fine-needle aspiration (FNA) or percutaneous biopsy of a perihilar mass should not be used for diagnosis due to the risk of tumor dissemination precluding liver transplant. If liver transplant is not an option, EUS-guided FNA can be diagnostic.

Surgical  resection

  • In patients undergoing resection for pCCA or dCCA, preoperative endoscopic biliary drainage of the remnant liver is recommended if biliary obstruction is present.
  • Surgical resection is the treatment of choice for early-stage pCCA and dCCA without any evidence of metastatic disease.
  • Patients diagnosed with pCCA/dCCA should be referred to a center with surgical expertise in hepatobiliary malignancies.

Neoadjuvant chemoradiation and LT

  • Liver transplant following neoadjuvant therapy should be considered for patients with pCCA (≤3 cm in radial diameter) that is unresectable or arising in the setting of PSC.
  • In patients with pCCA being evaluated for LT, EUS–fine-needle aspirationof regional lymph nodes should be performed to exclude patients with metastases before neoadjuvant therapy is initiated. Operative staging after completion of neoadjuvant therapy and before liver transplantation to assess regional hepatic lymph node involvement and peritoneal metastases is required.

Systemic  therapy

  • Systemic chemotherapy is the first-line treatment of advanced CCA. Gemcitabine plus cisplatin is the standard of care for newly diagnosed patients.
  • Upon progression on gemcitabine and platinum chemotherapy, the combination of FOLFOX is appropriate second-line therapy.
  • Next generation sequencing should be considered at diagnosis to guide second-line treatment options.
  • Patients with advanced CCA should be considered for referral to a center with expertise in hepatobiliary malignancies and available clinical trials.

Recommendation Grading

Overview

Title

Primary Sclerosing Cholangitis and Cholangiocarcinoma

Authoring Organization

Publication Month/Year

September 9, 2022

Document Type

Guideline

Country of Publication

US

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient, Operating and recovery room

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D018281 - Cholangiocarcinoma, D002761 - Cholangitis, D015209 - Cholangitis, Sclerosing

Keywords

cholangitis, Cholangiocarcinoma

Source Citation

Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD Practice Guidance on Primary Sclerosing Cholangitis and Cholangiocarcinoma. Hepatology. 2022 Sep 9. doi: 10.1002/hep.32771. Epub ahead of print. PMID: 36083140.