Association of serum zinc levels with liver function and survival in patients awaiting liver transplantation.

PURPOSE: Zinc is an important trace element with catalytic and defensive functions. We assessed the impact of zinc deficiency in patients with end-stage liver disease awaiting liver transplantation. METHODS: Serum zinc levels were measured at the time of evaluation for liver transplantation (n = 368). Patients were dichotomized in two groups based on low and normal zinc serum levels. RESULTS: Serum zinc levels are tightly associated with liver function as patients with low zinc levels (n = 226) had a higher Model for End-Stage Liver Disease (MELD) score (15.0 [5.0-40.0]) than patients with normal zinc (n = 142) levels (9.0 [6.0-34.0]; p < 0.00). Multivariate analysis demonstrated that serum zinc levels function as an independent predictor of hepatic decompensation (hydropic decompensation: odds ratio [OR] 0.82; 95% confidence interval [CI] 0.70-0.96; p = 0.015; hepatic encephalopathy: OR 0.80; 95% CI 0.71-0.90; p = 0.000; spontaneous bacterial peritonitis: OR 0.85; 95% CI 0.72-1.00; p = 0.047; hepatorenal syndrome: OR 0.83; 95% CI 0.72-0.95; p = 0.011). Actuarial survival free of liver transplantation was reduced for low-zinc patients (26.7 ± 4.0 months; 95% CI 18.8-34.6) compared to patients with normal zinc levels (30.9 ± 3.0 months; 95% CI 24.9-36.9; p = 0.008). Reduction of zinc levels for patients on the transplantation list resulted in a 28.3-fold increased risk of death/liver transplantation (95% CI 3.2-244.8, p < 0.001). CONCLUSIONS: Serum zinc levels are associated with reduced survival in end-stage liver disease patients. Whether or not zinc supplementation might be beneficial for patients on a liver transplantation list requires further study.

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

BACKGROUND AND 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. .