MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis - PubMed (original) (raw)

MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis

Bo-Xun Jin et al. Sci Rep. 2015.

Abstract

An important unresolved clinical issue is to distinguish hepatitis B virus (HBV) infection caused chronic hepatitis and their corresponding liver cirrhosis (LC). Recent research suggests that circulating microRNAs are useful biomarkers for a wide array of diseases. We analyzed microRNA profiles in the plasmas of a total of 495 chronic hepatitis B (CHB) patients, LC patients and healthy donors and identified 10 miRNAs that were differentially expressed between CHB and LC patients. Our logistic models show that three panels of miRNAs have promising diagnostic performances in discriminating CHB from LC. Blinded tests were subsequently conducted to evaluate the diagnostic performances in clinical practice and a sensitivity of 85% and specificity of 70% have been achieved in separating CHB from LC pateints. The expression levels of some circulating miRNAs were significantly correlated with HBV DNA load and liver function, such as prothrombin activity (PTA) and levels of alanin aminotransferase (ALT), albumin (ALB) and cholinesterase (CHE). Our results provide important information for developing novel diagnostic tools for distinguishing chronic HBV hepatitis and their corresponding cirrhosis.

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Figures

Figure 1

Figure 1. Profiling of miRNAs.

(a) Study design, Chronic hepatitis B (CHB) patients, liver cirrhosis (LC) patients and healthy controls (HC) were recruited for the discovery (15/group), training (50/group), validation (100/group) phases, and the blinded test. Individual miRNAs in the plasma were measured using quantitative realtime-PCR assay. (b) Profiling of miRNAs in training phase of HBV infected patients. (c) Profiling of miRNAs in validation phase of HBV infected patients. MiRNAs with significantly different expression levels between CHB, LC and HC of training phase (b) and validation phase (c) were shown. MiRNAs up indicates up-regulation while down meant down-regulation. Lined showed same miRNAs had different expression levels in different groups.

Figure 2

Figure 2. Expression of plasma miRNAs among study cohorts in training phase.

Relative expression levels of the miRNAs in plasma and ROC analysis with individual miRNAs and combined miRNA panel between LC and CHB patients (a), LC patients and HC (b), and CHB patients and HC (c) in training phase. P values were calculated using the Mann-Whitney test and p were all <0.01. Logistic regression indicates a linear combination of miRNAs.

Figure 3

Figure 3. Expression of miRNAs among study subjects in the validation phase.

Relative expression levels of the miRNAs in plasma and ROC analysis with combined miRNA panel between LC and CHB patients (a), LC patients and HC (b), and CHB patients and HC (c) in validation phase. P values were calculated using the Mann-Whitney test and p were all <0.01. Logistic regression indicates a linear combination of miRNAs.

Figure 4

Figure 4. Correlations of miRNAs expression and liver function in patients of validation phase.

Correlations of miRNAs expression and PTA (a), CHE (b), ALB (c) and TBIL(d) levels in LC patients, and correlation of miRNA expression and ALT (e) levels in CHB patients. Y axis represents relative expression levels of each miRNA in the corresponding subjects. P values were calculated using the Mann-Whitney test and p < 0.05 was significant.

Figure 5

Figure 5. Comparison of miRNAs in different status of CHB and LC patients.

(a) 4 miRNAs, miR-29c-3p, miR-106b-5p, miR-122-5p and miR-146a-5p were significantly upregulated in Child-Pugh A LC patients (p < 0.05) compared with Child-Pugh B/C LC patients. (b,c) According to serum levels of HBV load, CHB patients and LC patients were separated into 2 groups, miR-122-5p was considerably up-regulated in CHB (p = 0.0015, b) or LC (p = 0.039, c) patients with high viral load than with low viral load. Y axis represents relative expression levels of each miRNA in the corresponding subjects. P values were calculated using the Mann-Whitney test and p < 0.05 was significant.

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