BACKGROUND & AIMS: Small duct primary sclerosing cholangitis (PSC) is phenotypically a mild version of large duct PSC, but it is unknown whether these phenotypes share aetiology. We aimed to characterize their relationship by investigating genetic associations in the human leucocyte antigen (HLA) complex, which represent the strongest genetic risk factors in large duct PSC. METHODS: Four classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped in 87 small duct PSC patients, 485 large duct PSC patients and 1117 controls across three geographical regions. RESULTS: HLA-DRB1*13:01 (OR = 2.0, 95% CI 1.2-3.4, P = 0.01) and HLA-B*08 (OR = 1.6, 95% CI 1.1-2.4, P = 0.02) were significantly associated with small duct PSC compared with healthy controls. Based on the observed frequency of HLA-B*08 in small duct PSC, the strongest risk factor in large duct PSC, an estimated 32% (95% CI 4-65%) of this population can be hypothesized to represent early stages or mild variants of large duct PSC. This subgroup may be constituted by small duct PSC patients with inflammatory bowel disease (IBD), which greatly resembled large duct PSC in its HLA association. In contrast, small duct PSC without IBD was only associated with HLA-DRB1*13:01(P = 0.03) and was otherwise distinctly dissimilar from large duct PSC. CONCLUSIONS: Small duct PSC with IBD resembles large duct PSC in its HLA association and may represent early stages or mild variants of large duct disease. Different HLA associations in small duct PSC without IBD could indicate that this subgroup is a different entity. HLA-DRB1*13:01 may represent a specific risk factor for inflammatory bile duct disease.
BACKGROUND & AIMS: Small duct primary sclerosing cholangitis (PSC) is phenotypically a mild version of large duct PSC, but it is unknown whether these phenotypes share aetiology. We aimed to characterize their relationship by investigating genetic associations in the human leucocyte antigen (HLA) complex, which represent the strongest genetic risk factors in large duct PSC. METHODS: Four classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped in 87 small duct PSCpatients, 485 large duct PSCpatients and 1117 controls across three geographical regions. RESULTS:HLA-DRB1*13:01 (OR = 2.0, 95% CI 1.2-3.4, P = 0.01) and HLA-B*08 (OR = 1.6, 95% CI 1.1-2.4, P = 0.02) were significantly associated with small duct PSC compared with healthy controls. Based on the observed frequency of HLA-B*08 in small duct PSC, the strongest risk factor in large duct PSC, an estimated 32% (95% CI 4-65%) of this population can be hypothesized to represent early stages or mild variants of large duct PSC. This subgroup may be constituted by small duct PSCpatients with inflammatory bowel disease (IBD), which greatly resembled large duct PSC in its HLA association. In contrast, small duct PSC without IBD was only associated with HLA-DRB1*13:01(P = 0.03) and was otherwise distinctly dissimilar from large duct PSC. CONCLUSIONS: Small duct PSC with IBD resembles large duct PSC in its HLA association and may represent early stages or mild variants of large duct disease. Different HLA associations in small duct PSC without IBD could indicate that this subgroup is a different entity. HLA-DRB1*13:01 may represent a specific risk factor for inflammatory bile duct disease.
Authors: Ulrika Broomé; Hans Glaumann; Eva Lindstöm; Lars Lööf; Sven Almer; Hanne Prytz; Hanna Sandberg-Gertzén; Stefan Lindgren; Frans-Thomas Fork; Gunnar Järnerot; Rolf Olsson Journal: J Hepatol Date: 2002-05 Impact factor: 25.083
Authors: J M Farrant; D G Doherty; P T Donaldson; R W Vaughan; K M Hayllar; K I Welsh; A L Eddleston; R Williams Journal: Hepatology Date: 1992-08 Impact factor: 17.425
Authors: E K K Henriksen; M K Viken; M Wittig; K Holm; T Folseraas; S Mucha; E Melum; J R Hov; K N Lazaridis; B D Juran; O Chazouillères; M Färkkilä; D N Gotthardt; P Invernizzi; M Carbone; G M Hirschfield; S M Rushbrook; E Goode; C Y Ponsioen; R K Weersma; B Eksteen; K K Yimam; S C Gordon; D Goldberg; L Yu; C L Bowlus; A Franke; B A Lie; T H Karlsen Journal: HLA Date: 2017-07-11 Impact factor: 4.513
Authors: John E Eaton; Bryan M McCauley; Elizabeth J Atkinson; Brian D Juran; Erik M Schlicht; Mariza de Andrade; Konstantinos N Lazaridis Journal: J Gastroenterol Hepatol Date: 2017-10 Impact factor: 4.029
Authors: Matthew A Morgan; Rachita Khot; Karthik M Sundaram; Daniel R Ludwig; Rashmi T Nair; Pardeep K Mittal; Dhakshina M Ganeshan; Sudhakar K Venkatesh Journal: Abdom Radiol (NY) Date: 2022-09-05