Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection

Cheng, Xiaoming; Uchida, Takuro; Xia, Yuchen; Umarova, Regina; Liu, Chun‐Jen; Chen, Pei‐Jer; Gaggar, Anuj; Suri, Vithika; Mücke, Marcus M.; Vermehren, Johannes; Zeuzem, Stefan; Teraoka, Yuji; Osawa, Mitsutaka; Aikata, Hiroshi; Tsuji, Keiji; Mori, Nozomu; Hige, Shuhei; Karino, Yoshiyasu; Chayama, Kazuaki; Liang, T. Jake

doi:10.1172/jci135616

Cited by 41 publications

(42 citation statements)

References 63 publications

(84 reference statements)

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“…87 This is along the line of another study showing that HBV reactivation after HCV clearance is mainly due to the diminishing of HCV induced IFN response. 97…”

Section: Ifn Mediated Inhibition Of Hdv Replicationmentioning

confidence: 99%

New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies

Zhang

Urban

2021

Journal of Hepatology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…87 This is along the line of another study showing that HBV reactivation after HCV clearance is mainly due to the diminishing of HCV induced IFN response. 97…”

Section: Ifn Mediated Inhibition Of Hdv Replicationmentioning

confidence: 99%

New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies

Zhang

Urban

2021

Journal of Hepatology

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“…To further explore the molecular mechanisms behind this viral interaction and resultant HBV reactivation, our recent in vitro and in vivo investigations were conducted with major inputs from virologists [18]. In co-infected cell culture and humanized mice, HBV replication was suppressed by HCV co-infection.…”

Section: Viral Interactions: With Emphasis On Mechanisms Of Hbv Reactmentioning

confidence: 99%

“…Until now, the mechanism of this HBV reactivation, post-HCV cure, remained an interesting mystery. Our recent study provided evidence that HBV suppression was attenuated when IFN signaling was blocked in vitro [18]. Clinically, HBV viremia, after initial suppression by HCV super-infection, rebounded following HCV clearance by DAA treatment and was accompanied by a reduced hepatic interferon response.…”

Section: Introductionmentioning

confidence: 96%

“…Management of HBV activity, including the prevention of HBV reactivation post HCV cure, is a clinical issue that needs to be dealt with in further clinical trials. The lack of supportive evidence is reflected by the differences among the recommendations by the EASL (European Association for the Study of the Liver), AASLD (American Association for the Study of Liver Diseases) or APASL (Asian Pacific Association for the Study of the Liver) community regarding the prevention of HBV reactivation in co-infected patients [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis C Virus and Hepatitis B Virus Co-Infection

Shih¹,

Liu

2020

Viruses

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Hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection can be encountered in either virus endemic countries. Co-infection can also be found in populations at risk of parenteral transmission. Previous studies demonstrated a high risk of liver disease progression in patients with HCV/HBV co-infection; thus, they should be treated aggressively. Previous evidence recommended therapy combining peginterferon (pegIFN) alfa and ribavirin for co-infected patients with positive HCV RNA. Recent trials further advise using direct-acting antivirals (DAAs) for the clearance of HCV in the co-infected patients. Reactivation of HBV has been observed in patients post-intervention, with higher risks and earlier onset in those having had HCV cured by DAA- versus pegIFN-based therapy. The mechanism of HBV reactivation is an interesting but unsolved puzzle. Our recent study revealed that in vitro HBV replication was suppressed by HCV co-infection; HBV suppression was attenuated when interferon signaling was blocked. In vivo, the HBV viremia, initially suppressed by the presence of HCV super-infection, rebounded following HCV clearance by DAA treatment and was accompanied by a reduced hepatic interferon response. In summary, major achievements in the treatment of HCV/HBV co-infection have been accomplished over the past 20 years. Future clinical trials should address measures to reduce or prevent HBV reactivation post HCV cure.

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“…One report suggests that interferon signaling induced by HCV suppresses HBV replication. Following antiviral treatment and elimination of HCV, IFN levels decrease and HBV reemerges 42 . A second paper suggests that HBV is only mildly affected by IFN signaling and coinfection with HCV has no effect on HBV replication 43 .…”

Section: Changes In Cell Signaling Pathwaysmentioning

confidence: 99%

What came first, the virus or the egg: Innate immunity during viral coinfections

Rippee-Brooks¹,

Marcinczyk

Lupfer

2020

Immunological Reviews

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Infections with any pathogen can be severe and present with numerous complications caused by the pathogen or the host immune response to the invading microbe. However, coinfections, also called polymicrobial infections or secondary infections, can further exacerbate disease. Coinfections are more common than is often appreciated. In this review, we focus specifically on coinfections between viruses and other viruses, bacteria, parasites, or fungi. Importantly, innate immune signaling and innate immune cells that facilitate clearance of the initial viral infection can affect host susceptibility to coinfections. Understanding these immune imbalances may facilitate better diagnosis, prevention, and treatment of such coinfections.

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Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection

Cited by 41 publications

References 63 publications

New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies

New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies

Hepatitis C Virus and Hepatitis B Virus Co-Infection

What came first, the virus or the egg: Innate immunity during viral coinfections

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