Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

Table 1 Hepatobiliary disorders associated with inflammatory bowel disease

Hepatobiliary disorders	Associated with
	Ulcerative colitis	Crohn’s disease
Primary sclerosing cholangitis (PSC)
Large duct PSC	+	+
Small duct PSC (‘pericholangitis’)	+	+
Cirrhosis	+	+
Hepatoma	+	+
Cholangiocarcinoma	+	+
Miscellaneous disorders
Fatty liver	+	+
Granulomas		+
Amyloidosis		+
Hepatic abscess		+
Gallstones		+
Autoimmune hepatitis	+
Primary biliary cirrhosis	(+)
Budd-Chiari syndrome	(+)	(+)

+: Definite association; (+): Possible association.

Table 2 Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis

Country of origin	Number of patients with ulcerative colitis	Percentage with primary sclerosing cholangitis
Oxford, UK[9]	681	2.9
Oslo, Norway[12]	336	4
Stockholm, Sweden[11]	1500	3.7 (5.5 in total colitis)

Table 3 Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis (PSC)

Institution (country of origin)	Number of patients with PSC	Percentage with IBD
Royal Free Hospital (UK)[17]	29	72
Mayo Clinic (USA)[18]	50	70
Huddinge (Sweden)	305	72
King’s College London (UK-children)	13	77
Okolicsanyi (Italy)[19]	82	54
Escorsell (Spain)	43	47
Okada (Japan)[20]	155	23

Table 4 Evidence for the influence of immune mechanisms on the aetiology of PSC

Humoral immunity	Increased circulating immune complexes
	Elevated immunoglobulin levels (IgG and IgM)
	Low titres of non-organ specific autoantibodies (ANA and SMA)
	High titres of antineutrophil antibodies
	Autoantibodies to BEC surface antigens
Cell mediated immunity	Decreased 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
	Increased circulating and tissue bound adhesion molecules
Immune effector mechanisms	Enhanced cytokine expression in the liver
Immunogenetic mechanisms	HLA associations

Table 5 Key HLA haplotypes associated with primary sclerosing cholangitis

Haplotype	Significance in PSC
B8-TNF*2-DRB3*0101-DRB1*0301-DQA1*0501-DQB1*0201	Strong association with disease susceptibility
DRB3*0101-DRB1*1301-DQA1*0103-DQB1*0603	Strong association with disease susceptibility
DRB5*0101-DRB1*1501-DQA1*0102-DQB1*0602	Weak association with disease susceptibility
DRB4*0103-DRB1*0401-DQA1*03-DQB1*0302	Strong association with protection against disease
MICA*008	Strong association with disease susceptibility

Table 6 Clinical, Endoscopic, and Histological findings that characterize IBD-PSC

Male predominance

Quiescent colitis

Pancolitis

Rectal sparing

Backwash ileitis

Pouchitis

Colorectal dysplasia/carcinoma

Different extracolonic manifestations