MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C - PubMed (original) (raw)

Kevin Appourchaux 1 2 3, Matthieu Resche-Rigon 5, Xavier Treton 6, Martine Lapalus 1 2 3, Charles-Henry Gattolliat 1 2 3, Emmanuelle Porchet 1 2 3, Michelle Martinot-Peignoux 1 2 3, Nathalie Boyer 1 2 3, Michel Vidaud 7, Pierre Bedossa 8, Patrick Marcellin 1 2 3, Ivan Bièche 7, Emilie Estrabaud 1 2 3, Tarik Asselah 1 2 3

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MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C

Kevin Appourchaux et al. Sci Rep. 2016.

Abstract

Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with chronic hepatitis B (CHB) and C (CHC). The expression of 13 fibrosis-related microRNAs (miRNAs) (miR-20a, miR-21, miR-27a, miR-27b, miR-29a, miR-29c, miR-92a, miR-122, miR-146a, miR-155, miR-221, miR-222, and miR-224) was analyzed in 194 serums and 177 liver biopsies of patients with either CHB or CHC to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3-F4). In CHB patients, the model (serum miR-122, serum miR-222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB-4 to discriminate in between mild and moderate fibrosis (F1-F2) and F3-F4 (AUC of CHB model: 0.85 vs APRI: 0.70 and FIB-4: 0.81). In CHC patients, the model (hepatic miR-122, hepatic miR-224, platelet count, albumin and alanine aminotransferase) was more accurate than both APRI and FIB-4 to discriminate in between patients with F3-F4 and F1-F2 (AUC of the CHC model = 0.93 vs APRI: 0.86 and FIB-4: 0.79). Most of the miRNAs tested were differentially expressed in patients with CHB and CHC. In particular, serum miR-122 was 28-fold higher in patients with CHB than in those with CHC. Both CHB and CHC models may help for the diagnosis of advanced fibrosis and cirrhosis (F3-F4).

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Figures

Figure 1

Figure 1. Differences in the expression of hepatic miRNAs according to the stage of fibrosis in patients with chronic hepatitis B and C.

The expression of hepatic miR-20a, miR-21, miR-29a, miR-92a, miR-122, miR-146a, miR-221, miR-222, miR-224 was assessed by RT-qPCR from 1 ng of cDNA and compared in patients with F3-F4 and F0-F1-F2, in chronic hepatitis B patients (A–I) and in those with chronic hepatitis C (J–R). The ΔCt (ΔCt = 2ΔCp,sample) of each miRNA was calculated and normalized to the ΔCt value of SNORD44 in each biopsy. The log expression of the ratio miRNA/SNORD44 is shown as dot plot, each dot represents one patient (mean and standard deviation). The Wilcoxon rank-sum test was used to compare miRNAs expression.

Figure 2

Figure 2. Differences of the expression of serum miRNAs according to the stages of fibrosis in patients with chronic hepatitis B and C.

The expression of serum miR-20a, miR-21, miR-29a, miR-92a, miR-122, miR-146a, miR-221, miR-222, miR-224 was assessed by RT-qPCR and compared in patients with F3-F4 and F0-F1-F2, in chronic hepatitis B patients (A–I) and in those with chronic hepatitis C (J–R). The ΔCt (ΔCt = 2ΔCp,sample) of each miRNA was calculated and normalized to the ΔCt value of the exogenous _C. elegans_-miR-39 (_cel_-miR-39) in each serum. The log expression of the ratio miRNA/_cel_-miR-39 is shown as dot plot, each dot represents one patient (mean and standard deviation). The Wilcoxon rank-sum test was used to compare miRNAs expression.

Figure 3

Figure 3. Comparison of the expression of serum and hepatic miRNAs in patients with chronic hepatitis B and C.

The expression of serum (A–I) and hepatic (J–R) expression of miR-20a, miR-21, miR-29a, miR-92a, miR-122, miR-146a, miR-221, miR-222 and miR-224 was assessed by RT-qPCR and compared in patients with CHC and CHB. (A–I) In serum samples, The ΔCt (ΔCt = 2ΔCp,sample) of each miRNA was calculated and normalized to the ΔCt value of the exogenous _C. elegans_-miR-39 (_cel_-miR-39) in each serum. The log expression of the ratio miRNA/_cel_-miR-39 is shown as dot plot, each dot represents one patient (mean and standard deviation). (J–R) In liver samples, the ΔCt (ΔCt = 2ΔCp,sample) of each miRNA was calculated and normalized to the ΔCt value of SNORD44 in each biopsy. The log expression of the ratio miRNA/SNORD44 is shown as dot plot, each dot represents one patient (mean and standard deviation). The log expression of the ratio miRNA/SNORD44 is shown as dot plot, each dot represents one patient (mean and standard deviation). The Wilcoxon rank-sum test was used to compare miRNAs expression.

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