Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection
Year: 2020
Type: article
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.
DOI: 10.1172/jci135616
Authors: Xiaoming Cheng, Takuro Uchida, Yuchen Xia, Regina Umarova, Chun-Jen Liu, Pei-Jer Chen, Anuj Gaggar, Vithika Suri, Marcus M. Mücke, 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
Institutions: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Hiroshima University, National Taiwan University, Gilead Sciences (United States), University Hospital Frankfurt, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Sapporo Kosei General Hospital
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Japan Agency for Medical Research and Development, Ministry of Education, India, Ministry of Science and Technology, Taiwan, National Taiwan University Hospital, Wuhan University, State Key Laboratory of Virology, National Institutes of Health, Japan Society for the Promotion of Science, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W3012248463