Introduction

A coronavirus strain known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread throughout the worldwide and emerged as a significant cause of morbidity and mortality. The outbreak of coronavirus disease-2019 (COVID-19) has been declared a pandemic on March 11, 2020 (1). On the other hand, with approximately 300 million people chronically infected worldwide, the hepatitis B virus (HBV) is a serious threat to public health (2). There have been problems in the follow-up of chronic diseases due to the quarantine of countries, the overcapacity of hospitals with COVID-19. Regarding chronic hepatitis B, Turkey is a middle -endemic region, because of that co-infection with COVID-19 and chronic hepatitis B is also common (3).

COVID-19 does not only affect the respiratory system. The cause of hepatic manifestations is unclear at this stage. Cholangiocytes and hepatocytes have entry cell receptors for SARS-CoV-2 known as angiotensin-converting enzyme 2 receptors (4). According to a recent study, asymptomatic liver function tests are elevated in 50% of patients hospitalized for COVID-19 (5). Possible causes of liver impairment are the direct cytopathic effect of the virus, ischemic liver injury due to hypoxia developing during the disease, and immune-mediated liver injury (6). Additionally, hepatitis B reactivation and drug hepatotoxicity may develop because of the drugs used for treating COVID-19. The management of SARS-CoV-2 and hepatitis B co-infection is challenging because of them (7).

There are many studies have evaluating the severity of COVID-19 in patients with chronic hepatitis B patients. Several studies have shown that COVID-19 is not severe in patients with chronic hepatitis B (7). However, the mortality of COVID-19 is higher in patients with advanced liver disease. Also, patients with advanced liver disease have a poor immune system, and as a result, they are a vulnerable population that should prioritize COVID-19 vaccines. There are inactivated coronavirus vaccine (Sinovac) and mRNA vaccine (Phizer-BionTech) in our country. In this study, we determined the vaccination preference and vaccination rates of chronic hepatitis B patients, as well as to examine the effect of co-infection on the course of the COVID-19.

Materials and Methods

Subjects

One hundred people were included in the study who had chronic hepatitis B. The diagnosis of chronic hepatitis B was made according to the European Association for the Study of the Liver 2020 hepatitis B guideline. Patients’ demographics and vaccination information were manually collected from electronic health records.

Ethical Approval

The study protocol was approved by the Ethics Committee of Kocaeli University (approval number GOKAEK-2022/10.10). Since the study was retrospective, informed consent was not obtained from the patients.

Statistical Analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences version 20.0. The values p<0.05 were considered statistically significant. Data are presented as mean and percentages. The Kolmogorov-Smirnov test was used to assess the normality of the distribution of the investigated parameters. All parameters in our study were not distributed normally. Differences were tested by Mann-Whitney U test and Wilcoxon test.

Results

One-hundred patients with chronic hepatitis B were included in our study. Among these patients, males (n=56, 56%) predominated over females (n=44, 44%). The mean age of the individuals was calculated as 44 years (range: 12-78). All patients were taken antiviral treatment. Elevated aspartate aminotransferase and alanine aminotransferase were recorded in patients on 7/18 and 2/18, respectively, during COVID-19. The demographics and medical findings of the individuals are shown in Table 1.

Of all chronic hepatitis B patients, 50 were vaccinated with mRNA vaccine (Pfizer-BioNTech, 50%), and 22 with inactivated coronavirus vaccine (Sinovac, 22%). While 11 people (11%) had mixed immunotherapy, 17 (17%) were unvaccinated. In the Pfizer-BioNTech vaccinated group, 15 individuals had COVID-19 after vaccination. In the Sinovac vaccinated group, there were 7 patients after vaccination. Four people who vaccinated with mixed immunotherapy had also COVID-19 disease after vaccines. The time between the vaccination and polymerase chain reaction (PCR) positivity is shown in Table 2. The mean day count between the last vaccine date and SARS-CoV-2 PCR positivity date 127 (Pfizer-BioNTech group), 64 (Sinovac group), and 91 (mixed vaccine group) days, respectively. Those vaccinated with Pfizer-BioNTech were statistically significantly less infected with COVID-19 after vaccination (p<0.05).

There were 53 patients with PCR-confirmed COVID-19. Among them, 9 patients were admitted to clinics and 4 to the intensive care unit due to hypoxia. Of 13 patients with severe disease, 5 had Sinovac, 2 had Pfizer-BioNTech, one had mixed, and 5 were unvaccinated. When the 2 patients who died were examined, it was found that 1 of them was unvaccinated and the other was inactivated coronavirus vaccine. Forty patients (74%) had mild disease. On the other hand, among patients with severe diseases, 10 of them had negative current HBV-DNA values.

Discussion

Data on the prevalence of COVID-19 and chronic hepatitis B confection are limited. In a meta-analysis conducted in China where chronic hepatitis B is hyperendemic, approximately 25,000 COVID-19 patients were examined, and the prevalence of co-infection was found to be 3% (8). Recent reports showed that about 2-11% of patients with COVID-19 had underlying chronic liver disease (9). Hepatic involvement in COVID-19 is multi-factorial. Many reasons such as the direct cytopathic effect of the virus, uncontrolled immune reaction, drug-related injury, sepsis, and hypoxia can cause damage in the spectrum from asymptomatic liver enzyme abnormalities to fatal acute liver injury. During this pandemic, hepatic dysfunction has been seen in 14-53% of patients (10).

In our study, although the number of patients is small, SARS-CoV-2 and hepatitis B co-infection do not affect the severe outcomes. Similar findings were found by Lv et al. (11), who discovered that COVID-19 patients with HBV infection had a lower risk of serious events such as intensive care unit admission or death. However, Jothimani et al. (10) said that COVID-19 may cause worsening of underlying chronic liver disease, leading to hepatic decompensation and acute-on-chronic liver failure, with higher mortality. In a study from China, where hepatitis B is highly endemic, COVID-19 is related to more severe outcomes in patients with chronic liver disease (8).

The administration of vaccines against SARS-CoV-2 will help control the pandemic, especially to populations at high risk of developing severe COVID-19. Although it varied according to the variants, the efficacy of CoronaVac and Pfizer-BioNTech vaccines was found to be 60% and 90%, respectively (12).

Study Limitations

Main limitations are the small number of our patients and the inability to do subgroup analyses.

Conclusion

The effect of COVID-19 and hepatitis B co-infection on the severity of COVID-19 and the long-term effects of vaccine-induced immunity in these patients will be guided by epidemiological studies. In our study post-vaccine COVID-19 disease and severity of disease are less in Pfizer-BioNTech vaccinated group. Additionally, co-infection with SARS-CoV-2 and hepatitis B has no impact on the more serious outcomes.

Ethics

Ethics Committee Approval: The study protocol was approved by the Ethics Committee of Kocaeli University (approval number GOKAEK-2022/10.10).

Informed Consent: Since the study was retrospective, informed consent was not obtained from the patients.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: F.M.K., Concept: S.A., Design: S.A., Data Collection and Processing: M.T.D., Analysis or Interpretation: S.A., Literature Search: M.T.D., Writing: M.T.D.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declare no financial support.