Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response

Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1–5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC

Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice

<p><i>Objective</i>: Evaluate the association between the multi-biomarker disease activity (MBDA) score and radiographic progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF)-α inhibitors.</p> <p><i>Methods</i>: Change (Δ) in modified total Sharp score (mTSS) over 52 weeks and disease activity scores were examined retrospectively by Spearman's rank correlation coefficient in patients (<i>N</i> = 83) with RA initiating TNF-inhibitor treatment. Relative risk (RR) of ΔmTSS >0.5 for low MBDA score and 28-joint count disease activity score (DAS28) categories and associations between ΔmTSS and MBDA score categories conditional on DAS28 categories were assessed.</p> <p><i>Results</i>: At 52 weeks, 34% of patients had ΔmTSS >0.5 and 12% had ΔmTSS >3. Strongest correlations were observed between ΔmTSS and MBDA score (<i>r</i> = 0.47) or DAS28 (<i>r</i> = 0.42) at Week 24 and for area under the curve at Week 52 (MBDA score: <i>r</i> = 0.44, DAS28: <i>r</i> = 0.41), all <i>p</i> < 0.001. At Week 24, RR of ΔmTSS >0.5 for moderate/high MBDA score (≥30) or DAS28 (>3.2) were 6.6 (<i>p</i> < 0.001) and 2.7 (<i>p</i> = 0.005), respectively. Low DAS28 had greater risk of ΔmTSS >0.5 at 52 weeks when MBDA score was ≥30 (<i>p</i> < 0.05).</p> <p><i>Conclusion</i>: Higher MBDA score or DAS28 at Week 24 was associated with greater radiographic progression over 52 weeks of TNF-inhibitor treatment. MBDA score improved risk discrimination for radiographic progression within DAS28 categories.</p