Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing Cholangitis (PSC) is a chronic, progressive
cholestatic liver disease characterized by inflammation, fibrosis,
and stricturing of medium and large bile ducts in both the intrahepatic
and extrahepatic biliary tree.
Clinical Manifestations
- Associated with inflammatory bowel disease (IBD), especially
ulcerative colitis, and autoimmune hepatitis (AIH)
- Symptoms include gradual onset of fatigue, anorexia, weight
loss, with later appearance of pruritus and intermittent
jaundice
- Common presentation includes cholangitis symptoms: right upper
quadrant (RUQ) pain, fever, and jaundice
- Early course is often asymptomatic; diagnosis may follow
abnormal lab findings
- Progressive disease leads to biliary cirrhosis and end-stage
liver disease
Laboratory Evaluation
- No specific lab marker unique to PSC
- Common findings: elevated alkaline phosphatase, direct
bilirubin, aminotransferases, and γ-glutamyl transpeptidase
(GGT)
- GGT is more reliable than ALP in children due to bone growth
confounders
- Pediatric-specific prognostic tool: SCOPE
Index (see below)
Radiographic Findings
- Cholangiography is the gold standard for
diagnosis
- ERCP findings:
- Irregular narrowing and multifocal strictures
- “Beaded appearance” due to alternating strictures and
dilations
- MRCP: Noninvasive imaging of intrahepatic
ducts; no therapeutic capability
Liver Biopsy
- Shows fibrous obliteration of small bile ducts
- Characteristic “onion skin” concentric fibrosis
- Used to confirm diagnosis, assess fibrosis, and evaluate AIH
overlap
Therapy and Management
- No curative medical therapy currently available
- Ursodeoxycholic acid (UDCA) and oral
vancomycin (OVT) may improve labs but not disease
progression
- Monitor for complications: portal hypertension, nutritional
deficiencies, fat-soluble vitamin deficiency
- Manage pruritus and cholangitis episodes
- Liver transplantation is the only definitive
treatment for end-stage liver disease
Epidemiology and Prognosis
- Prevalence: 0.2–1.5 per 100,000 children
- Male predominance; typically diagnosed after age 10
- Variable prognosis: some remain stable, others progress
rapidly
- PSC recurrence post-transplant occurs in ~20% of cases
SCOPE Index in Pediatric PSC
The SCOPE Index (Sclerosing Cholangitis
Outcomes in Pediatrics) is a validated prognostic tool designed to
predict disease progression in children diagnosed with Primary
Sclerosing Cholangitis (PSC).
Purpose
- Predicts risk of transplant or death (TD)
- Estimates likelihood of hepatobiliary complications
(HBCs) such as portal hypertension, cholangitis, and
cholangiocarcinoma
Components
The index uses five clinical variables:
- Total bilirubin
- Albumin
- Platelet count
- Gamma-glutamyl transferase (GGT)
- Cholangiographic findings (large-duct vs small-duct PSC)
| Variable |
Value Range |
Points |
| Total Bilirubin (mg/dL) |
< 1.0 |
0 |
| 1.0–2.9 |
1 |
| ≥ 3.0 |
2 |
| Albumin (g/dL) |
≥ 3.5 |
0 |
| 2.5–3.4 |
1 |
| < 2.5 |
2 |
| Platelet Count (×10⁹/L) |
≥ 150 |
0 |
| 100–149 |
1 |
| < 100 |
2 |
| Gamma-Glutamyl Transferase (GGT) (U/L) |
< 100 |
0 |
| 100–399 |
1 |
| ≥ 400 |
2 |
| Cholangiographic Phenotype |
Small-duct PSC |
0 |
| Cholangiographic Phenotype |
Large-duct PSC |
1 |
Risk Stratification
| Total Score |
Risk Group |
Annual Risk of Transplant or Death |
Annual Risk of Hepatobiliary Complications |
| 0–2 |
Low |
<1% |
2% |
| 3–5 |
Medium |
3% |
6% |
| 6–9 |
High |
9% |
13% |
Clinical Utility
- Helps clinicians and families understand prognosis
- Supports shared decision-making and timing of interventions
- Useful for stratifying patients in clinical trials
Reference:
Deneau MR, et al. "Development and Validation of a Pediatric
Primary Sclerosing Cholangitis Risk Score (SCOPE Index)." Hepatology.
2021;74(1):112–125. DOI: 10.1002/hep.31701
AASLD review: Primary sclerosing cholangitis
-Cholestatic liver disease characterized by inflammation and
fibrosis of the extrahepatic and intrahepatic bile ducts
–Thought to be immune mediated in nature
–Pathogenesis may be due to bile acid toxicity, diminished biliary
bicarbonate umbrella, aberrant lymphocyte homing, leaky gut, and
intestinal dysbiosis
-76% of children with PSC have concomitant inflammatory bowel
disease
Definition
PSC overlap syndromes occur when diagnostic features of both PSC and
other immune mediated liver diseases such as autoimmune hepatitis,
autoimmune pancreatitis, and rarely in adults primary biliary
cirrhosis occur
Large duct PSC is defined as disease that is noted on imaging
studies
Small duct PSC is a disease variant characterized by cholestatic and
histologic features of PSC but normal bile ducts on cholangiography
At diagnosis, dominant strictures are typically present in up to 45%
of adults but only 4% of children. Children typically have
more features of PSC/AIH overlap. Alkaline phosphatase is not
a reliable marker in children and so GGT is more commonly used as a
biomarker for clinical and research practices.
Diagnosis
Patients must have labs demonstrating cholestasis, cholangiography
showing characteristic bile duct changes with multifocal strictures
and segmental dilations of the intrahepatic and extrahepatic bile
ducts, and exclusion of secondary causes of sclerosing cholangitis.
Consider the diagnosis in patients with elevated AST, ALT, GGT, and
AP.
Right upper quadrant ultrasound should be performed to exclude
biliary obstruction, if obstruction is not found then
cholangiography is the next step. MRCP is preferred given that
it is noninvasive and less expensive and there are no associated
risks of pancreatitis, however, ERCP allows direct visualization of
the bile ducts and can be utilized for therapeutic interventions
(tissue sampling, removal of mechanical obstruction such as stones,
and dilation of symptomatic or dominant strictures)
Screening for IBD with EGD and colonoscopy with biopsies should be
done at the same time
AASLD guidelines recommend that all patients with PSC undergo liver
biopsy to evaluate for evidence of AIH
Lab work including total IgG, ANA, anti-smooth muscle antibody, and
anti-LKM antibody should be sent.
Histology consistent with PSC/AIH overlap can include:
Periductal concentric fibrosis
Portal and interface mixed inflammation
Plasma cell infiltrate
*If Cholangiography is normal but labs are consistent with PCS,
recommend Liver Bx to evaluate for small duct PSC*
Treatment
Ursodeoxycholic acid (well tolerated, but long term bebfits unclear)
Steroids and other immunosuppresive agents have not demonstrated any
improvement in disease activity or in the outcome of PSC (but often
receive treatment due to overlap with AIH)
Oral vancomycin (no formal randomized controlled trials)
Liver Transplant indicated if complicated by portal hypertension and
end stage liver disease
Prognosis
SCOPE (Sclerosing cholangitis outcomes in pediatrics)
References:
https://www.aasld.org/liver-fellow-network/core-series/clinical-pearls/peeling-back-layers-pediatric-primary-sclerosing