<i>Fut2</i> genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis

Rupp, Christian; Friedrich, Kilian; Folseraas, Trine; Wannhoff, Andreas; Bode, Konrad A.; Weiss, Karl Heinz; Schirmacher, Peter; Sauer, Peter; Stremmel, Wolfgang; Gotthardt, Daniel

doi:10.1111/apt.12663

Cited by 28 publications

(18 citation statements)

References 38 publications

(85 reference statements)

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“…In agreement with previous reports, 4,9,18,19 we detected Candida species, especially C albicans in bile samples. However, the study by Lenz et al 9 did not identify previous endoscopic intervention as a risk factor for fungobilia, even though the level of significance showed a trend toward association.…”

Section: Discussionsupporting

confidence: 93%

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment

et al. 2016

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The aim of this study was to determine the antibiotic susceptibility profiles of bacteria in bile samples and to analyze the clinical relevance of the findings as only limited information about risk factors for elevated frequence of bacterial and fungal strains in routinely collected bile samples has been described so far.A prospective cohort study at a tertiary care center was conducted. Seven hundred forty-four patients underwent 1401 endoscopic retrograde cholangiographies (ERCs) as indicated by liver transplantation (427/1401), primary sclerosing cholangitis (222/1401), choledocholithiasis only (153/1401), obstruction due to malignancy (366/1401), or other conditions (233/1401). Bile samples for microbiological analysis were obtained in all patients.The 71.6% (823/1150) samples had a positive microbiological finding, and 57% (840/1491) of the bacterial isolates were gram-positive. The main species were Enterococcus spp (33%; 494/1491) and Escherichia coli (12%; 179/1491). Of the samples, 53.8% had enteric bacteria and 24.7% had Candida spp; both were associated with clinical and laboratory signs of cholangitis (C-reactive proteins 35.0 ± 50.1 vs 44.8 ± 57.6; 34.5 ± 51.2 vs 52.9 ± 59.7; P < 0.001), age, previous endoscopic intervention, and immunosuppression. Multi-resistant (MR) strains were found in 11.3% of all samples and were associated with clinical and laboratory signs of cholangitis, previous intervention, and immunocompromised status. In subgroup analysis, strain-specific antibiotic therapy based on bile sampling was achieved in 56.3% (89/158) of the patients. In cases with a positive bile culture and available blood culture, blood cultures were positive in 29% of cases (36/124), and 94% (34/36) of blood cultures had microbial species identical to the bile cultures.Bactobilia and fungobilia can usually be detected by routine microbiological sampling, allowing optimized, strain-specific antibiotic treatment. Previous endoscopic intervention, clinical and laboratory signs of cholangitis, and age are independent risk factors. MR bacteria and fungi are an evolving problem in cholangitis, especially in immunocompromised patients.

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Section: Discussionsupporting

confidence: 93%

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment

et al. 2016

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“…An intriguing study identified an association between fucosyltransferase 2 ( FUT2) genotype and episodes of cholangitis, fungobilia (biliary Candida infections), and dominant stenosis, suggesting that FUT2 may be a marker of ‘host microbial diversity’ and ‘disease progression’ in PSC. These results support other studies suggesting that FUT2 variants ‘garden’ the microbiome in both healthy and IBD populations 101-103 .…”

Section: Clinical Applications and Genetic Testingsupporting

confidence: 91%

Genetics of Inflammatory Bowel Diseases

2015

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In this Review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and non-coding genetic variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding genetic variation. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-early onset, more severe cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer genetic testing, as well as the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.

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“…In addition to bacterial infections common for PSC, fungal infections are becoming an increasingly recognized complication associated with a poor prognosis. The frequency of fungal pathogens in the bile fluid ranges from 15 to 50%, depending on the underlying disease [ 19 ],[ 22 ],[ 29 ]. The persistence of candida has already been associated with a worse prognosis in neonates [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis

et al. 2014

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BackgroundCandidiasis is commonly observed in patients with primary sclerosing cholangitis (PSC), but the clinical risk factors associated with its presence have not been fully investigated. In this study, we aimed to analyse the incidence, risk factors, and transplantation-free survival in primary sclerosing cholangitis (PSC) patients with persistent biliary candidiasis.MethodsWe retrospectively analysed patients diagnosed with PSC who were admitted to our department during 2002 to 2012. One-hundred fifty patients whose bile cultures were tested for fungal species were selected, and their clinical and laboratory parameters were investigated. The results of endoscopic retrograde cholangiography (ERC) and bile cultures were analysed using chart reviews. The cases of biliary candidiasis were sub-classified as transient or persistent.ResultsThirty out of 150 (20.0%) patients had biliary candidiasis. Although all patients demonstrated comparable baseline characteristics, those with biliary candidiasis showed significantly reduced transplantation-free survival (p < 0.0001) along with a markedly elevated frequency of cholangiocarcinoma (CCA) (p = 0.04). The patients were further sub-classified according to the transient (15/30) or persistent (15/30) nature of their biliary candidiasis. A subgroup analysis showed reduced survival with a greater necessity for orthotopic liver transplantation (OLT) only in patients with persistence of Candida (p = 0.007). The survival in the patients with transient biliary candidiasis was comparable to that in candidiasis-free patients. In a multivariate regression analysis that included Mayo risk score (MRS), sex, age, dominant stenosis, inflammatory bowel disease, autoimmune hepatitis overlap syndrome, and number of times ERC was performed, biliary candidiasis was an independent risk factor for reduced survival (p = 0.008). Risk factors associated with acquisition of biliary candidiasis were age at PSC diagnosis and number of ERCs.ConclusionsThe persistence of biliary candidiasis is associated with markedly reduced transplantation-free survival in PSC patients. By contrast, actuarial survival in patients with transient biliary candidiasis approaches that for patients without any evidence of biliary candidiasis. Further studies on the treatment of persistent biliary candidiasis in patients with PSC are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0562-8) contains supplementary material, which is available to authorized users.

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Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis

Cited by 28 publications

References 38 publications

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment

Genetics of Inflammatory Bowel Diseases

Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis

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