Topic Highlight
Copyright ©2008 The WJG Press and Baishideng.
World J Gastroenterol. Jun 7, 2008; 14(21): 3350-3359
Published online Jun 7, 2008. doi: 10.3748/wjg.14.3350
Table 1 Causes and mimics of secondary sclerosing cholangitis (SSC)
CausesSurgical trauma to bile ducts
Ischaemic injury eg after transplantation
Hepatic arterial chemotherapy eg floxuridine
Intraductal gallstones[3]
Viral or bacterial infection eg CMV or cryptosporidiosis
Caustic injury eg formalin treatment of hydatid disease
Congenital abnormalities eg cystic fibrosis
Conditions mimicking sclerosing cholangitis on imagingMalignancy eg metastatic carcinoma
Hypereosinophilic syndrome
Choledochal cyst
Table 2 The features of primary sclerosing cholangitis compared with classical autoimmune disease
CharacteristicClassical autoimmune diseaseImmune-mediated inflammatory disease (such as IBD, psoriasis)Primary sclerosing cholangitis
AgeChildren and adultsChildren and adultsChildren and adults
SexFemale predominanceNo gender predilectionMale predominance
AutoantibodiesYes (pathogenic)Yes (markers)Yes (probably markers)
Associated autoimmune diseaseYesYesYes
HLA associations (class I and II)YesYesYes
Response to immunosuppressionUsually goodOften goodGood in children
Poor in adults
Table 3 Autoantibody prevalence in primary sclerosing cholangitis
AntibodyPrevalence (%)
Anti-nuclear antibody (ANA)7-77
Anti-smooth muscle antibody (ASMA)13-20
Anti-endothelial cell antibody (AECA)35
Anti-cardiolipin antibody4-66
Rheumatoid factor15
Table 4 Key HLA haplotypes in PSC[27]
HLA haplotypesOdds ratio
3 HLA haplotypes associated with an increased riskB8-MICA*008-TNFA*2-DRB3*0101-DRB1*0301-DQB1*02012.69
3 HLA haplotypes associated with reduced risk (protective)DRB4*0103-DRB4*0401-DQA1*03-DQB1*03020.26
Table 5 Comparison of PSC and AIP-SC
GenderM:F = 2:1Probably some male predominance[818587]
Clinical presentationUsually insidious. Sometimes with obstructive jaundice secondary to cholangiocarcinoma.Mild abdo/Back pain
Sometimes with short history of obstructive jaundice due to CBD stricture
Associated inflammatory bowel diseaseYesNo
Cholangiographic findingsDiffuse changes throughout intra- and extrahepatic bile ducts. Abnormalities in pancreatic duct common.Pancreatic duct strictures or narrowing. Often stricture of distal 1/3 of common bile duct. Intrahepatic duct changes less common.
Blood chemistry dataOften cholestatic but bilirubin usually near normal.May be cholestatic. Bilirubin often high
AutoantibodiesAtypical pANCA plus range of othersAntibodies to carbonic anhydrase II plus range of others[808184]
ImmunoglobulinsIgG4 levels normalIgG4 levels usually elevated[82]
HistologyAbsence of plasma cells positive for IgG4 on immunostainingIgG4 positive plasma cells present in bile ducts and portal tracts[79]
Liver biopsy stagingRange of Ludwig staging including higher stages eg III or IVLudwig staging usually only I or II[86]
TreatmentUrsodeoxycholic acid ± biliary drainage for dominant stricturesSystemic steroid therapy usually leads to complete resolution of symptoms and signs of disease. Occasionally patients relapse and require longer courses of steroids
Table 6 Evidence for the influence of immune mechanisms on the aetiology of PSC
Evidence for the influence of immune mechanisms
Humoral immunityIncreased circulating immune complexes
Elevated immunoglobulin levels (IgG and IgM)
Low titres of non-organ specific autoantibodies (ANA and SMA)
High titres of antineutrophil nuclear antibody (ANNA)
Cell mediated immunityDecreased levels of circulating peripheral CD8+ve Tcells
Portal T cell and NK cell infiltrate
Increased activated and memory T cells
Restricted T cell receptor repertoire (Vβ3)
Aberrant expression of HLA-DR on BEC
Coexpression of costimulatory molecules and HLA-DR on BECs
Abnormal expression of adhesion molecules on biliary epithelial cells
Abnormal expression of chemokine ligands on biliary epithelial cells
Immune effector mechanismsEnhanced cytokine expression in the liver
Immunogenetic mechanismsHLA associations