Hepatitis B virus (HBV) infection is a disease condition caused by the hepatitis B virus, of the Hepadnaviridae family. It causes viral hepatitis which can be acute or chronic. HBV infection is said to be chronic when it persists for more than 6 months and there is an increased likelihood of it developing into cirrhosis or hepatocellular carcinoma.
Hepatitis B Virus
The virus is most frequently passed from mother to child during childbirth and the early years of life. It can also be contracted by improper injection procedures, exposure to sharp objects, or contact with blood or other bodily fluids during intercourse with an infected partner.
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Those who get infected at an earlier age are at a high risk of developing chronic hepatitis later in life. Less than 10% of individuals infected beyond five progress to the chronic form, compared to over 90% of those infected during or shortly after birth. HBV infection is one of the vaccine-preventable diseases which is why it is recommended that newborns are vaccinated at birth.
HBV infection is a global health burden and 1.2 million new infections are recorded each year. In 2022, reports have it that 254 million people were diagnosed with chronic HBV infection. In the same year, approximately 1.1 million deaths were recorded.
Functional cure with IFN-I
No specific treatment is needed for acute illness as most adults recover spontaneously, however, antiviral therapy is required in situations where the disease course becomes aggressive or in immunocompromised people. The treatment of chronic infections is usually necessary to prevent the occurrence of liver cirrhosis and hepatocellular carcinoma.
Treatment modalities include antiviral therapies like tenofovir and lamivudine and immune modulators like pegylated interferon. There are currently no treatments that may completely eradicate the infection, but these medications can minimize liver damage by preventing the virus from multiplying. Current therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic HBV infection include interferon I (IFN-I) and nucleos(t)ide analogs (NA).
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Compared to NA, IFN-I is presently the only medication that may effectively cure chronic HBV infection, known as a functional cure, it can be characterized as the absence of HBsAg in the serum. Through binding to its receptors, IFNAR1 and IFNAR2, IFN-I has the ability to inhibit HBV DNA replication and regulate cytotoxic T-cell immune responses. The latter is associated with reduced HBsAg in the serum which is a marker of functional cure. Despite all these effects, IFN-I still doesn’t give enough desired effects.
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Aspirin causes stable levels of IFNAR1 and IRF9
The degradation of IFNAR1 is said to be a hindrance to the optimum functioning of IFN-I due to the negative feedback mechanism. Ying Miao et al discovered that not only does IFNAR1 degradation attenuate the action of IFN-I but also the de-phosphorylation of an associated protein, IRF9, still via a negative feedback mechanism, further weakens the action of IFN-I.
Mice were injected with 50 μg per gram body weight of aspirin (low dose) and 2 hours later, IFN-I for 6 hours. They discovered that aspirin caused the levels of IFNAR1 to be stable after the administration of IFN-I. They also found that the expressions of IRF9 were constantly maintained. The combination therapy of aspirin and IFN-I significantly reduced HBsAg levels in the serum and in total, 13 out of 15 participants achieved a functional cure in 48 weeks.
Clinical significance
The study shows that aspirin is efficacious in potentiating the actions of IFN-I to achieve a functional cure. From the observations noticed, researchers suggest that a combination therapy of aspirin and IFN-I could be an effective therapeutic regimen for patients with chronic HBV infection. Also, aspirin was very beneficial because it reduced fever in most participants and this can improve clinical outcomes and patient satisfaction.
Subsequently, more studies are needed to further assess the safety of higher doses of aspirin. Also, it is also necessary to find out whether aspirin can be used with other therapies like nucleos(t)ide analogs.
References
Miao, Y., Yuan, Y., Chen, Y., Liu, J., Huang, F., Zhang, T., Zhang, R., Zhao, Q., Cui, Q., Tian, W., He, W., Zuo, Y., Zheng, Z., Zhao, Z., Li, M., Qian, F., Zhu, L., Zhu, C., & Zheng, H. (2024). medRxiv, 2024.06.14.24308555. https://doi.org/10.1101/2024.06.14.24308555
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