MiRNome Profiling of Circulating Extracellular Vesicles in Patients With Chronic Hepatitis D Undergoing Pegylated Interferon Alpha Treatment

Abstract

ABSTRACTMicro‐RNAs (miRNAs) are involved in the modulation of viral replication and host immune antiviral response. Using next‐generation sequencing, we investigated the miRNome profile of circulating extracellular vesicles in 20 patients with chronic hepatitis D virus (HDV) infection undergoing pegylated interferon alpha (Peg‐IFNα) treatment. Circulating miRNAs' expression was analysed according to virologic response (i.e., HDV RNA clearance maintained at least 6 months after the end of therapy). Overall, 8 patients (40%) achieved a virologic response to Peg‐IFNα treatment. At baseline, 14 miRNAs were differentially expressed between responders and non‐responders; after 6 months of Peg‐IFNα treatment, 7 miRNAs (miR‐155‐5p, miR‐1246, miR‐423‐3p, miR‐760, miR‐744‐5p, miR‐1307‐3p and miR‐146a‐5p) were consistently de‐regulated. Among de‐regulated miRNAs, miR‐155‐5p showed an inverse correlation with HDV RNA (at baseline: rs = −0.39, p = 0.092; at 6 months: rs = −0.53, p = 0.016) and hepatitis B surface antigen (HBsAg) (at baseline: rs = −0.49, p = 0.028; at 6 months: rs−0.71, p < 0.001). At logistic regression analysis, both miR‐155‐5p (at baseline: OR = 4.52, p = 0.022; at 6 months: OR = 5.30, p = 0.029) and HDV RNA (at baseline: OR = 0.19, p = 0.022; at 6 months: OR = 0.38, p = 0.018) resulted significantly associated to virologic response. Considering that Peg‐IFNα still has a relevant role in the treatment of patients with chronic hepatitis D infection, the assessment of EV miR‐155‐5p may represent an additional valuable tool for the management of HDV patients undergoing Peg‐IFNα treatment.