Diminished Hepatic IFN Response Following HCV Clearance Triggers HBV Reactivation in Coinfection

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2020 Mar 13

PMID 32163375

Citations 25

Authors

Xiaoming Cheng

Takuro Uchida

Yuchen Xia

Regina Umarova

Chun-Jen Liu

Pei-Jer Chen

Anuj Gaggar

Vithika Suri

Marcus M Mucke

Johannes Vermehren

Stefan Zeuzem

Yuji Teraoka

Mitsutaka Osawa

Hiroshi Aikata

Keiji Tsuji

Nami Mori

Shuhei Hige

Yoshiyasu Karino

Michio Imamura

Kazuaki Chayama

T Jake Liang

Affiliations

Soon will be listed here.

Abstract

In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.

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