The Interplay Between Hepatitis B Virus (HBV) and SARS-CoV-2: Implications for Coinfection and Disease Management


Hepatitis B virus (HBV) is a member of the Hepadnaviridae family and is responsible for a staggering number of chronic hepatitis infections worldwide.

According to the latest data from the World Health Organization (WHO), approximately 296 million individuals are chronically infected with HBV [1].

Upon HBV infection, the interaction between the virus and the host’s immune response determines whether the infection will resolve or progress to chronic hepatitis B [3].

The current classification for HBV chronic infection consists of five distinct phases, which are not necessarily sequential but are based on HBeAg seropositivity, as well as levels of HBV DNA and alanine aminotransferase (ALT) in the serum [3].

These phases include HBeAg-positive chronic HBV infection, HBeAg-positive chronic hepatitis B, HBeAg-negative chronic HBV infection, HBeAg-negative chronic hepatitis B, and the HBsAg-negative phase [2,3].

Regardless of the phase, a common feature of chronic Hepatitis B is the presence of covalently closed circular DNA (cccDNA) within the nucleus of hepatocytes [5]. This cccDNA acts as a template for HBV transcripts, which are subsequently translated into the main proteins of the virus [3,4]. Additionally, cccDNA is the primary cause of HBV reactivation (HBVr) at any phase, particularly under conditions of immunosuppression [6-9].

In late 2019, the world faced a significant global public health crisis in the form of the Covid-19 pandemic. The virus responsible for the disease, SARS-CoV-2, not only affects the respiratory system but has also been reported to cause liver injury with abnormal liver biochemistry [10,11,12,16].

Several mechanisms have been proposed to explain liver injury during Covid-19, including the direct cytopathic effect of SARS-CoV-2 through angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors on cholangiocytes and hepatocytes [13]. Other mechanisms involve liver injury caused by severe inflammation, hypoxia, drug toxicity from Covid-19 treatments, and vascular changes associated with coagulopathy [14,15].

Considering that both HBV and SARS-CoV-2 can potentially induce liver injury, numerous studies have aimed to investigate cases of coinfection to understand the impact of one virus on the natural history of chronic HBV and the influence of HBV seropositivity on the severity of Covid-19 infection [17].

In an effort to contribute to this ongoing debate, we present a case study of a patient who experienced HBV reactivation shortly after a Covid-19 infection, without receiving any systemic immunosuppressive medication.

In conclusion, based on the low risk of HBV reactivation triggered by inhaled corticosteroids (ICS) and in line with other reported cases, we attribute our patient’s HBV reactivation to the recent Covid-19 infection.

This highlights the importance of closely monitoring individuals who are positive for HBsAg (HBV surface antigen) in the event of SARS-CoV-2 infection, even in the absence of systemic immunosuppressive treatment. To fully understand whether HBV reactivation may result from viral interactions with non-hepatotropic viruses like SARS-CoV-2, further research is required.

This knowledge will not only enhance our understanding of viral pathogenesis but also help guide clinical management and preventive strategies.

One aspect that requires attention is the impact of SARS-CoV-2 infection on the natural history of chronic HBV. Does Covid-19 infection accelerate the progression of chronic hepatitis B or alter the course of the different phases of HBV infection? Longitudinal studies involving a larger cohort of patients with chronic HBV and concurrent Covid-19 infections are necessary to answer these questions.

Additionally, investigating the influence of HBV seropositivity on the severity and clinical outcomes of Covid-19 is crucial for understanding the interplay between these two viruses.

Clinical surveillance and monitoring of individuals with chronic HBV who contract Covid-19 should be prioritized. Close observation of liver function tests, including ALT levels, HBV DNA levels, and serological markers, is necessary to promptly detect HBV reactivation and implement appropriate interventions.

It is important to note that HBV reactivation can occur even in the absence of systemic immunosuppression, as observed in the case presented. This emphasizes the need for vigilance and regular monitoring in HBsAg-positive individuals during Covid-19 infection.

In terms of preventive measures, vaccination against both HBV and Covid-19 is essential. Universal vaccination programs for HBV have shown great success in reducing the burden of chronic hepatitis B worldwide. Similarly, the development and distribution of effective vaccines against SARS-CoV-2 have played a crucial role in mitigating the impact of the Covid-19 pandemic.

Encouraging vaccination in high-risk populations, including individuals with chronic HBV, can provide dual protection against these viral infections and potentially reduce the risk of complications and disease progression.

Furthermore, the findings from studies investigating the relationship between HBV and SARS-CoV-2 can contribute to our understanding of viral pathogenesis and immunology. Viral interactions, particularly between two distinct viruses, provide valuable insights into host-virus interactions, immune responses, and the mechanisms underlying viral persistence and clearance.

These insights can potentially inform the development of novel therapeutic approaches, such as combination antiviral therapies or immunomodulatory interventions, that target multiple viruses simultaneously.

The case presented in this study underscores the need for continued research on the interplay between HBV and SARS-CoV-2 infections. It highlights the potential for HBV reactivation following Covid-19 infection and emphasizes the importance of monitoring individuals with chronic HBV during the course of Covid-19, even in the absence of systemic immunosuppressive treatment.

Further investigation is warranted to elucidate the mechanisms underlying these viral interactions, assess their impact on disease outcomes, and develop effective management strategies. By expanding our knowledge in this area, we can improve the care and outcomes of individuals with coinfections and contribute to global efforts in combating both HBV and Covid-19.

reference link : doi:10.20944/preprints202306.1305.v1


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