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Serum miRNA-122 is an Independent Biomarker of Survival in Patients with Primary Sclerosing Cholangitis

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Kilian Friedrich1, Carina Baumann1, Andreas Wannhoff1, Christian Rupp1, Arianeb Mehrabi2, Karl Heinz Weiss1, Daniel Gotthardt1

1) University Hospital of Heidelberg, Department IV, Im Neuenheimer Feld 410, Heidelberg,
2) Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg Germany

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.272.cho

Background & Aims: The disease course of primary sclerosing cholangitis (PSC) is variable and difficult to predict. MicroRNA-122 (miR-122) is associated with various liver diseases. We investigated the value of miR-122 as a biomarker for the disease course of PSC.
Methods: We determined serum miR-122 levels in a long-term, prospective cohort of 114 PSC patients and
a second validation cohort.
Results: Based on miR-122 levels, PSC patients were assigned to low or high level miR-122 groups. Kaplan- Meier analysis showed significantly impaired actuarial transplant-free survival for PSC patients in the low miR-122 group (mean: 46.1 ± 4.1 months; 95% confidence intervals [CI]: 38.1–54.2) compared to the high miR- 122 group (mean: 95.2 ± 7.9 months; 95% CI: 79.5–110.8; p = 0.034). Using a multivariate Cox’s proportional hazards model approach, Mayo-Risk score (odds ratio [OR]: 1.47; 95% CI: 1.13‒1.92; p = 0.004), the presence of dominant strictures (OR: 2.62; 95% CI: 1.00‒5.55; p = 0.004), and serum miR-122 levels (OR: 1.19; 95% CI: 1.00‒1.43; p = 0.045) were independent risk factors associated with reduced actuarial transplant-free survival. We were able to confirm this finding in a second, independent cohort of PSC patients (low miR-122 group: mean survival: 13.1 ± 5.2 months; 95% CI: 2.8–23.4; high miR-122 group: mean: 28.62 ± 4.2 months; 95% CI: 20.3–37.0; p = 0.018).
Conclusions: We identified miR-122 as a novel, independent prognostic biomarker associated with improved survival in PSC patients. It is unknown whether exogenous miR-122 might influence the disease course of PSC patients.
Key words: miR-122 – primary sclerosing cholangitis – actuarial survival free of liver transplantation – biomarker.
Abbreviations: AP: alkaline phosphatase; CT: cycle threshold; DS: dominant stenosis; ERC: endoscopic retrograde cholangiography; IBD: inflammatory bowel disease; miR-122: microRNA-122; PSC: primary sclerosing cholangitis; RT-qPCR: quantitative real-time reverse transcription polymerase chain reaction.