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. 2024 Jun 20;16(6):992.
doi: 10.3390/v16060992.

Hepatitis C Virus as a Possible Helper Virus in Human Hepatitis Delta Virus Infection

Affiliations

Hepatitis C Virus as a Possible Helper Virus in Human Hepatitis Delta Virus Infection

Maria Grazia Crobu et al. Viruses. .

Abstract

Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through hepatitis B virus (HBV)-unrelated ways, but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.

Keywords: HDV-RNA; anti-HBc; co-infection; helper virus; hepatitis B virus; hepatitis C virus; hepatitis D virus; human immunodeficiency virus; propagation; superinfection.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Timeline with relevant data from the clinical history of the patient, which resulted anti-HD positive. The upper part of the figure depicts data with respect to HIV-RNA (blue line) and HCV-RNA (orange line) trends; the purple asterisks represent the serialized controls of virological tests for HBV (HBV-DNA and complete serology, which were always completely negative). The lower part of the figure depicts the treatment regimens she underwent for both HIV (in green) and HCV (in orange) infections. The arrow refers to the time when the patient was sampled for the present study (April 2023), as reported in Table 1. Abbreviations: abacavir (ABC); atazanavir (ATV); cobicistat (COBI); darunavir (DRV); dolutegravir (DTG); emtricitabine (FTC); hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency virus (HIV); lamivudine (3TC); nevirapine (NVP); pegylated interferon (PEG-IFN); ribavirin (RBV); ritonavir (RTV); sofosbuvir (SOF); tenofovir disoproxil fumarate (TDF); velpatasvir (VEL); zidovudine (ZDV).
Figure 2
Figure 2
Timeline with relevant data from the clinical history of the anti-HD positive patient’s husband. The upper part of the figure depicts data with respect to HIV-RNA (blue line) and HCV-RNA (orange line) trends. Asterisks represent the serialized controls of virological tests for HBV (HBV-DNA and complete serology); color code: purple means completely negative serology, red means seroconversion to both anti-HBs (73 IU/mL) and anti-HBe (weak positivity). The lower part of the figure depicts the treatment regimens he underwent for both HIV (in green) and HCV (in orange) infections. The blue arrow refers to the last blood biochemical workup immediately prior to the diagnosis of lung cancer and that was considered for this research as reported in Table 1 (September 2020), while the red arrow refers to the patient’s date of death (July 2021). Abbreviations: anti-hepatitis e antigen antibodies (anti-HBe); anti-HBsAg antibodies (anti-HBs); cobicistat (COBI); darunavir (DRV); dolutegravir (DTG); efavirenz (EFV); emtricitabine (FTC); hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency virus (HIV); indinavir (IDV); lamivudine (3TC); ledipasvir (LDV); pegylated interferon (PEG-IFN); ribavirin (RBV); ritonavir (RTV); tenofovir disoproxil fumarate (TDF); zidovudine (ZDV).

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