Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?

van Munster, Kim N.; Bergquist, Annika; Ponsioen, Cyriel Y.

doi:10.1016/j.jhep.2023.09.031

Cited by 19 publications

(2 citation statements)

References 158 publications

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“…The majority of patients with PSC are initially diagnosed with extensive colitis [ 72 ]. Currently, there is an ongoing discussion regarding whether PSC represents an extraintestinal manifestation of IBD or if PSC and IBD are distinct entities that share a common susceptibility leading to a dual phenotype [ 19 , 73 ]. This study reinforces the causative link between genetically predicted IBD and PSC.…”

Section: Discussionmentioning

confidence: 99%

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study

Gao,

Peng,

Wang

et al. 2024

J Transl Med

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Background The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization. Methods Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD. Results Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423–1.843, P = 2.506 × 10− 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055–2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131–0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023–1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094–1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127–1.303, P = 2.015 × 10− 7) and RA (OR = 1.417, 95%CI 1.193–1.683, P = 7.193 × 10− 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005–1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017–1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019–1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560–0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699–0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462–0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164–1.346, P = 1.394 × 10− 9), RA (OR = 1.543, 95%CI 1.279–1.861, P = 5.728 × 10− 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141–0.510, P = 6.172 × 10− 5) were positively associated with an increased risk of PSC. Conclusions Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.

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Section: Discussionmentioning

confidence: 99%

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study

Gao,

Peng,

Wang

et al. 2024

J Transl Med

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“…Although there is a strong correlation between the two diseases, a number of clinical trials have confirmed that drugs suitable for IBD have very limited benefits for the treatment of PSC, which suggests that pathophysiology of PSC differs from that of IBD. 62,63 It is very important to optimize the design of new drugs and to explore appropriate therapeutic drug targets. There is no satisfactory animal model of PSC disease, which limits the progress of new drug development.…”

Section: Discussionmentioning

confidence: 99%

Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going?

Luo,

2024

J Clin Transl Hepatol

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Cholestatic liver disease is a group of diseases in which bile acid accumulates in the liver for various reasons, resulting in abnormal liver biochemical indicators and histological damage. Cholestasis can be divided into intrahepatic cholestasis and extrahepatic cholestasis, which will contribute to liver damage and progress to liver fibrosis and cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis are the two most typical cholestatic liver diseases. Ursodeoxycholic acid is currently the first-line treatment for PBC, while obeticholic acid, budesonide and fibrates have also shown good potential in the treatment of PBC. There are currently no official drugs approved to treat primary sclerosing cholangitis, and the use of ursodeoxycholic acid may have certain clinical benefits. At present,

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Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study

Yasuda,

Shiokawa,

Kuwada

et al. 2024

J Gastroenterol

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Background Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities. Methods Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA. Results Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn’s disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001). Conclusions We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.

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Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?

Cited by 19 publications

References 158 publications

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study

Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going?

Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study

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