ACG Clinical Guideline: Primary Sclerosing Cholangitis—2015

February 18th, 2020

Note: ACG recommendations in italics

DIAGNOSIS:
- In general, PSC diagnosed in the setting of chronic cholestatic liver test abnormalities (particularly elevated
ALP), along with evidence of multifocal strictures of intrahepatic and extrahepatic bile ducts
- Signs/symptoms:
o Fatigue is most common finding
o Pruritis?Biliary obstruction
o RUQ pain + fevers?acute cholangitis
- Serum tests:
o ALP and GGT typically > AST and ALT
o Bilirubin and albumin normal at initial diagnosis
o Hypergammaglobulinemia is uncommon, but IgM alone can be elevated in 50% of patients
o IgG4 should be checked at least once in patients with PSC
 Elevated in ~10% of patientspotentially different subset of disease, more rapidly
progressive in absence of treatment
 Respond to corticosteroids
o AMA should be obtained to exclude PBC
o ANA, ANA, and ASMA are not specific for PSC
- PSC-Autoimmune hepatitis Overlap Syndrome
o Prevalence ~10%
o Should test for autoimmune hepatitis in patients who are diagnosed <25 years of age or with AST/ALT
higher than expected (typically 5x ULN)
- MRCP is preferred over ERCP to establish diagnosis of PSC
- Liver biopsy is recommended to make diagnosis of patients with PSC if small-duct disease is suspected (i.e.
imaging negative) and to exclude other conditions (i.e. autoimmune hepatitis overlap)
o The characteristic periductal concentric “onion-skin” fibrosis that is not frequently found, will most
likely be reported as “compatible” with PSC
- Differential: Secondary sclerosing cholangitis, cholangiocarcinoma, IgG4-associated cholangitis,
histiocytosis X, autoimmune hepatitis, HIV syndrome, bile duct strictures, choledocholithiasis, PBC,
papillary tumors
MEDICAL THERAPY:
- No established medical therapy for PSC
- Ursodeoxycholic acid (UDCA)
o Has been used in PBC patients—moderate doses (13mg-15mg/kg/day) showed improvement in
labs, but not clinically
o Higher dose of 17-23mg/kg/day showed worse outcomes
o Due to recent studies that show that patients with PSC who have normalized liver enzymes
(whether on their own or with UDCA) have better prognosis
 Some practitioners are using 20mg/kg/day dosing
 Do not use doses >28mg/kg/day
- Immunosuppressants
o Have been tested, no obvious clinical benefits
 AZT, budesonide, docosahexaenoic acid, MTX, metronidazole, minocycline, MMF, nicotine,
pentoxifylline, pifrenodone, prednisolone, tacrolimus
- Pruritis:
ACG Clinical Guideline: Primary Sclerosing Cholangitis—2015
February 18th, 2020

o Typically worse at night and in warm, humid climates

o Treat mild pruritis with topical emollients or anti-histamines
o Treat more severe pruritis with bile-acid sequestrants
 First-line: Cholestyramine 4-16g per day
 Second-line therapies:
 Rifampin 150-300mg BID
 Naltrexone up to 50mg/day
 Sertraline 75-100mg daily
 Phenobarbitl 90mg QHS
- Vancomycin:
o Case-series data and reports that oral vancomycin is associated with improvement in clinical
symptoms and liver enzymes in some patients (more pediatric than adult)
o PMID 30838381: Retrospective chart review of 8 UC-PSC patients who received PO vancomycin for
symptomatic UC
 Mayo score reduction from 6-11 to 0-2 after 6-12 months
- Other monitoring:
o PSC patients with advanced liver disease should be screened for fat-soluble (A, D, E, K) vitamin
deficiencies
o PSC patients should undergo DEXA at diagnosis and repeat at 2-4 year intervals
o PSC patients should be screened for varices with any sign of advanced liver disease or platelets
<150,000
 Some PSC patients develop pre-cirrhotic portal hypertension due to nodular regenerative
hyperplasia or obliterative venopathy
 Exception points are not offered for these patients
PROCEDURES:
- ERCP is recommended in patients with dominant stricture and pruritis, and/or cholangitis to relieve
symptoms
o Dominant stricture = extrahepatic (<1.5mm in the CBD) and large intrahepatic bile ducts (<1.0mm)
o No standardized techniques for endoscopic treatment of dominant strictures yet
 Routine stenting after dilation is not required unless short-term stenting is necessary due to
severe structuring disease
 Stent placement can lead to more frequent complications of cholangitis than dilation alone,
but short-term stenting can reduce risk of stent occlusion without this risk of cholangitis
o Treatment of dominant strictures may improve prognosis as chronic biliary obstruction leads to
progressive hepatic fibrosis and cirrhosis
o Any dominant stricture on imaging in PSC patients should have an ERCP with cytology, biopsies, and
FISH to exclude diagnosis of cholangiocarcinoma
 In a case-series of 128 patients with PSC, 80/128 (63%) of patients had dominant
strictures, and of those, 21/80 (26%) developed cholangiocarcinoma
 Early evaluation of dominant strictures after diagnosis is key—almost half of malignancies
are diagnosed within 4 months after initial diagnosis of PSC
 Cholangioscopy allows for direct biliary visualization and directed biopsies
 Confocal laser microscopy has 98% sensitivity, but is not widely studied in dominant
strictures yet
o PSC patients who undergo ERCP show have antibiotic prophylaxis to prevent post-ERCP cholangitis
 Pre-op antibiotics followed by 3-5-day course of antibiotics (quinolones or cephalosporins)
ACG Clinical Guideline: Primary Sclerosing Cholangitis—2015
February 18th, 2020

- Percutaneous therapy
o Can be considered in patients with altered anatomy that prevents successful ERCP (i.e. Roux-en-Y)
or patients who failed ERCP
 Failed ERCP: Intrahepatic strictures that cannot be reached by ERCP or very tight strictures
that cannot be traversed by endoscopic wires/dilators
o Second-line due to increased risk of hepatic arterial injury, hemobilia, cholangitis
- Surgical biliary reconstruction no longer used due to increased rates of mortality, cholangitis, post-
operative scarring that makes liver transplantation difficult
-
LIVER TRANSPLANTATION:
- Natural history of PSC is variable, but median time for progression of disease from diagnosis to death or
liver transplantation is 10-12 years
o Transplantation offers 5-year survival of 80-85%
- Liver transplant is recommended over medical or surgical therapy in PSC patients with decompensated
cirrhosis to prolong survival when possible
- Patients should be referred for liver transplant when MELD >14
o Exception points can be reviewed for:
 Recurrent episodes of cholangitis with >2 episodes of bacteremia or >1 episode of sepsis
 Cholangiocarcinoma <3cm in diameter, without evidence of metastasis, undergoing
treatment through an IRB-approved clinical trial
 Intractable pruritis
- Recurrence of PSC after liver transplantation is common, up to 20% of patients at 5 years

PSC and IBD:

- Up to 5% of IBD patients have PSC, but up to 80% of PSC patients have IBD
o Prevalence may be underestimated due to normal-appearing mucosa and asymptomatic patients
with biopsies showing histologic colitis
- Unique phenotype:
o Younger patients and often quiescent or asymptomatic
o Predilection for right-sided colitis and sparing of the rectum
o Patients more likely to have pouchitis after IPAA
o Portal hypertension leads to increased risk of stomal and peristomal varices
o More likely to have UC or Crohn’s disease with colonic involvement; small-bowel only Crohn’s
disease is not usually associated with PSC
- Full colonoscopy with biopsies is recommended in patients with PSC regardless of presence of symptoms to
assess for associated colitis at the time of PSC diagnosis (conditional recommendation, moderate quality of
evidence)
o Some advocate for repeating the exam every 3-5 years in those without prior evidence of colitis (weak
recommendation, low quality evidence)
- Increased risk of colonic malignancy
o 4-5x higher in IBD/PSC patients than IBD alone
o Mechanism unknown, but ?increased exposure to toxic bile acids (such as deoxycholic acid)
o Annual colon surveillance (preferably with chromoendoscopy) is recommended in PSC patients with
colitis at the time of diagnosis
o No studies show UDCA benefit for chemoprevention
ACG Clinical Guideline: Primary Sclerosing Cholangitis—2015
February 18th, 2020

HEPATOBILIARY MALIGNANCIES AND GALLBLADDER DISEASE:

- Increased risk of cholangiocarcinoma, diagnosis is challenging (benign stricture versus cholangio?)
o 10-year cumulative risk of 8%
o Consider screening for cholangiocarcinoma with regular cross-sectional imaging with ultrasound or
MRI and serial CA 19-9 every 6-12 months)
- Increased risk of HCC
o Very infrequent, screen as per cirrhosis
- Increased risk of gallstones and gallbladder cancer
o Cholecystectomy should be performed in PSC patients with gallbladder polyps >8mm to prevent
development of gallbladder adenocarcinoma