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DOI: 10.1055/s-0035-1559098
Serum miRNA-122 is an independent biomarker of survival in patients with primary sclerosing cholangitis
Background & Aims: The disease course of primary sclerosing cholangitis (PSC) is variable and difficult to predict. MicroRNA-122 (miR-122) is associated with various hepatic disorders. 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. Based on miR-122 levels, PSC patients were assigned to low or high level miR-122 groups.
Results: 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.
Cox univariate analysis OR [95% CI] |
Cox multivariate analysis OR [95% CI] |
|
miRNA-122 |
1.27 [1.04 – 1.39] |
1.19 [1.00 – 1.43] |
Serum MRS |
1.35 [1.06 – 1.73] |
1.47 [1.13 – 1.92] |
IBD |
2.36 [.966 – 5.77] |
2.54 [.94 – 6.82] |
Dominant stricture |
2.00 [.903 – 4.44] |
2.62 [1.00 – 5.55] |