ABSTRACT
Objective To measure the expression of circulating microRNA (miRNA)in patients with hepatitis B virus (HBV)-related liver failure and its relationship with disease prognosis.Methods The miRNA expressions in serum of 5 patients with HBV-related liver failure and 5 healthy control subjects were compared using Exiqon miRCURY LNATM miRNA microarray.The sera from 20 patients with chronic hepatitis B (CHB),20 patients hepatitis B related cirrhosis,50 patients with HBV-related liver failure and 40 healthy persons in Ruijin Hospital were collected.The relative expression of miRNA-595 was measured using quantitative real-time polymerase chain reaction (PCR).The relative expressions of miRNAs among groups were analyzed using student t test,the correlations were analyzed by Pearson and Spearman correlation.Results Microarray informed that 92 miRNAs changed significantly in patients with HBV-related liver failure,and miRNA-595 increased most significantly.The results of real-time PCR showed that the relative expressions of miRNA-595 ,miRNA-300 and miRNA-122 were 6.03 (t=3.134, P =0.003),3.12 (t=7.221 ,P <0.01)and 2.77 (t=2.671 ,P =0.021),which were higher compared to those in healthy control group.In the analysis of the relationship between miRNA-595 expression and disease prognosis in patients with HBV-related liver failure,the relative expressions of miRNA-595 in patients with CHB,hepatitis B related cirrhosis and HBV-related liver failure were 2.26 (t =3.780,P =0.001),3.32 (t = 6.111 ,P < 0.01)and 6.03 (t = 3.134,P = 0.003),respectively,which were all increased compared to that of the healthy control.The relative expression of miRNA-595 of patients with HBV-related liver failure was 2.66 times (t=2.450,P =0.043)higher than that of patients with CHB. When dividing patients according to prothrombin activity,miRNA-595 increased significantly in patients with early stage liver failure.When dividing patients according to model of end-stage liver disease (MELD) score,MELD score was positive correlated with the expression of miRNA-595 when MELD score was under 30 (r=0.673,P =0.004).The expression of serum miRNA-595 in survival group (11 .08,n=23) was higher than that in non-survival group (3.67,n = 27,t =4.309,P =0.041).Conclusions The expressions of miRNA595 ,miRNA-300 and miRNA-122 are all increased in patients with HBV-related liver failure,especially the expression of circulating miRNA-595 at early stage of the disease.The miRNA-595 may be used as a new serum biomarker for monitoring the severity of disease.