Z Gastroenterol 2015; 53 - KG072
DOI: 10.1055/s-0035-1559098

Serum miRNA-122 is an independent biomarker of survival in patients with primary sclerosing cholangitis

K Friedrich 1, C Baumann 1, A Wannhoff 1, C Rupp 1, K Weiss 1, W Stremmel 1, D Gotthardt 1
  • 1Universitätsklinik Heidelberg, Abteilung für Gastroenterologie, Heidelberg, Deutschland

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.

Tab. 3: Features associated with death/Ltx in PSC patients on liver transplant list according to Cox's proportional hazards model.

Cox univariate analysis OR [95% CI]

Cox multivariate analysis OR [95% CI]

miRNA-122

1.27 [1.04 – 1.39]
p = 0.009

1.19 [1.00 – 1.43]
p = 0.045

Serum MRS

1.35 [1.06 – 1.73]
p = 0.015

1.47 [1.13 – 1.92]
p = 0.004

IBD

2.36 [.966 – 5.77]
p = 0.059

2.54 [.94 – 6.82]
p = 0.064

Dominant stricture

2.00 [.903 – 4.44]
p = 0.087

2.62 [1.00 – 5.55]
p = 0.049