Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, and Current Management

Gochanour, Eric; Jayasekera, Channa R.; Kowdley, Kris V.

doi:10.1002/cld.902

Cited by 37 publications

(34 citation statements)

References 15 publications

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“…Notably in the largest study to date, UDCA (13-15mg/kg/day) has been shown to decrease the risk graft dysfunction and death, as well as the risk of rPBC. The study also found that the use of cyclosporine had an additive effect to UDCA in reducing recurrence, graft loss, and mortality [115] . Thus, while the treatment of rPBC is not established, preventative UDCA and possibly the use of cyclosporine-based immunosuppression are useful strategies to prevent recurrence.…”

Section: Management and Outcomes After Pbc Recurrencementioning

confidence: 71%

“…Immunosuppression: Cyclosporine use decreased risk as compared to tacrolimus [110][111][112]107,110] Genetic predisposition [108] Increased donor age, warm and cold ischemic time [109,112,114] Preventative use of UDCA, and in combination with cyclosporine, post LT reduced the risk of rPBC [115] rPSC 20% to 25% [2] Diagnosis of PSC prior to LT and cholangiography showing non-anastomotic intrahepatic and/or extrahepatic bile duct strictures with irregularities and beading occurring more than 90 days post-LT Or Liver biopsy demonstrating fibrous cholangitis and/or fibro-obliterative lesions [127] Inflammatory bowel disease [128][129][130] Acute cellular rejection [131,132,134,135] Donor-recipient CMV mismatch [133] Poor graft quality [133] Pre-transplant MELD > 24 [133,135] Cholangiocarcinoma [134,135] Higher donor age [134] No proven therapies Symptomatic management ALT: Alanine aminotransferase; AST: aspartate transaminase; CMV: cytomegalovirus; MELD: model for end stage liver disease; MMF: mycophenolate mofetil; UDCA: ursodeoxycholic acid.…”

Section: Incidence and Diagnosis Of Aih Recurrencementioning

confidence: 99%

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Autoimmune liver diseases, hepatocellular carcinoma, and recurrence of autoimmunity post-liver transplantation

Wang¹,

Dong²,

Montaño-Loza³

et al. 2021

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Liver transplantation for the autoimmune liver diseases (AILD), which includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), is indicated in the setting of decompensated cirrhosis, liver failure, and hepatocellular carcinoma (HCC). The risk of HCC is thought to be low in AILD, though data on the risk factors and predictors of HCC are limited in this population. Recurrence of AILD can occur in over half of the patients, complicating the post-transplant course. The pathogenesis of recurrent AILD involves a complex interaction of genetic and environmental influences, as well as a variety of clinical risk factors. Graft and patient survival are negatively impacted by recurrent AILD and the optimal approach to the treatment of AILD recurrence is the subject of ongoing research. This review will address the current literature on the risk of HCC in AILD, as well as the development and management of recurrent AILD post-liver transplantation.

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Section: Management and Outcomes After Pbc Recurrencementioning

confidence: 71%

Section: Incidence and Diagnosis Of Aih Recurrencementioning

confidence: 99%

Autoimmune liver diseases, hepatocellular carcinoma, and recurrence of autoimmunity post-liver transplantation

Wang¹,

Dong²,

Montaño-Loza³

et al. 2021

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“…The risk for hepatobiliary malignancies is increased [ 6 , 7 , 8 ]. Pharmaceutical treatment is currently not available and mean liver transplantation-free survival is 14.5 years [ 9 , 10 ]. SC-CIP occurs after long-term intensive care treatment with the need for catecholamine treatment and invasive ventilation.…”

Section: Introductionmentioning

confidence: 99%

The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

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The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

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“…Ursodeoxycholic acid (UDCA) is the most widely used therapy for several liver disorders, including chronic cholestatic and autoimmune liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) [ 1 , 2 , 3 , 4 ]. Initially, UDCA was thought to reduce the toxicity of the bile acid (BA) pool by replacing the hydrophobic acids by more hydrophilic and less toxic derivatives [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…The unique FDA-approved alternative to UDCA, namely obeticholic acid (OCA), exerts beneficial effects in PBC and PSC treatment [ 22 ], but the occurrence of important side effects (such as pruritus), also limits its clinical use. Thus, important pharmacological needs remain unmet in the treatments of these chronic cholestatic conditions [ 3 , 4 , 19 , 22 ]. However, given the benefits of UDCA therapy in responsive PBC patients and its accessibility, pharmacological strategies aimed at increasing the effectiveness of the drug (such as combination therapies) could rapidly lead to the implementation of better treatments for PBC and PSC.…”

Section: Introductionmentioning

confidence: 99%

Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid

et al. 2021

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Ursodeoxycholic acid (UDCA) is the first line therapy for the treatment of cholestatic and autoimmune liver diseases. Its clinical use is currently limited by a significant proportion of non-responder patients. Polyunsaturated fatty acids (n-3 PUFAs) possess important anti-inflammatory properties and protect liver cells against bile acid (BA)-induced toxicity. The present study was designed to rapidly evaluate whether combining n-3 PUFAs (i.e., eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids) to UDCA would provide additional benefits when compared to the drug alone. The parameters evaluated were (i) the expression of genes governing BA synthesis, transport, and metabolism; (ii) the prevention of BA-induced apoptosis and endoplasmic reticulum (ER)-stress; and (iii) the control of BA- and LPS-dependent inflammation. In the absence of n-3 PUFAs, most of the parameters investigated were unaffected by UDCA or were only altered by the higher dose (500 µM) of the drug. By contrast, in the presence of EPA/DHA (50/50 µM), all parameters showed a strongly improved response and the lowest UDCA dosage (50 µM) provided equal or better benefits than the highest dose used alone. For example, the combination EPA/DHA + UDCA 50 µM caused comparable down-regulation of the CYP7A1 gene expression and of the BA-induced caspase 3 activity as observed with UDCA 500 µM. In conclusion, these results suggest that the addition of n-3 PUFAs to UDCA may improve the response to the drug, and that such a pharmaco-nutraceutical approach could be used in clinic to open the narrow therapeutic dose of UDCA in cholestatic liver diseases.

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Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, and Current Management

Abstract: http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-gochanour a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-kowdley an interview with the author

Cited by 37 publications

References 15 publications

Autoimmune liver diseases, hepatocellular carcinoma, and recurrence of autoimmunity post-liver transplantation

Autoimmune liver diseases, hepatocellular carcinoma, and recurrence of autoimmunity post-liver transplantation

The Gut-Liver Axis in Cholestatic Liver Diseases

Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid

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