3 years into the COVID-19 pandemic, it has had a significant impact on human health and economic development. Based on WHO statistics, as of April 22, there are approximately 497 million confirmed patients and 6.179 million deaths in the world because of COVID-19.
Novel Coronavirus (SARS-CoV-2) shares a partly similar structure with the SARS virus 18 years ago, while it is more infectious and accommodates better to temperature changes. Besides, seasonal changes have little sway over the virus. As a consequence, people lay their hope of eradicating the pandemic on vaccines.
During the research and development of the vaccines, enterprises like Pfizer, Moderna, Johnson & Johnson, AstraZeneca, and Sinovac have contributed much to the combat of the disease and also acquired a great revenue from the new COVID-19 vaccines. Among those vaccines, the mRNA vaccine has risen sharply and set off a global boom in development for its short R&D cycle and high protection rate. COVID-19 mRNA vaccine (BNT162b2, brand name: Comirnaty), jointly developed by Pfizer/BioNTech, is one of the earliest widely used mRNA COVID-19 vaccines globally, which has gained 36.781 billion US dollars in profit last year.
However, on April 21, a case released in the Journal of Hepatology, an international authoritative journal in the field of liver diseases, struck BNT162b2. According to the research, BNT162b2 may cause a T cell-mediated autoimmune hepatitis.
Autoimmune hepatitis is a chronic progressive liver inflammatory disease mediated by the autoimmune reaction. Its clinical features are elevated serum transaminase of various levels, hypergammaglobulinemia, and positive autoantibody. Its histological features are interfacial hepatitis mainly infiltrated by lymphocytes and plasma cells. Severe cases can rapidly progress to liver cirrhosis and liver failure.
This clinical research from Germany has disclosed a bimodal attack of acute hepatitis after vaccinating two doses of the Pfizer mRNA vaccine (the attacks occur after two vaccinations). This male patient is 52 years old with no other medical history except hypothyroidism.
Diagnosis
The patient began to show symptoms of progressive nausea, fatigue, anorexia, and pruritus nearly 10 days after the vaccination of the first dose of BNT162b2. He experienced jaundice next and paid a visit to a primary health physician on the 25th day after vaccination. Liver function examination (LFT) revealed acute mixed hepatocyte/cholestatic hepatitis (ALT: 2130 U/l, AP: 142 U/l, γ-GT: 217 U/l, bilirubin 7.7 mg/dl).
Serological and/or PCR tests excluded the possibility of viral hepatitis A, B, C, and E, as well as cytomegalovirus and Epstein-Barr virus infections. The patient recovered quickly without special treatment and was discharged 3 days later. The level of liver enzymes of the patient gradually decreased to the normal condition over the next 2 weeks.
Subsequently, the patient was inoculated with the second dose of BNT162b2 41 days after the first one. After 20 days, the patient relapsed with acute mixed hepatitis. The patient's liver function improved after oral taking budesonide daily. However, his disease relapsed after 39 days, and finally eased under the treatment of systemic steroids combined with ursodeoxycholic acid.
Autoimmune serological examination showed that the patient had mild hyperglobulinemia, antinuclear antibody (ANA), antimitochondrial M2 antibody (AMA-M2), and anti-smooth muscle antibody was critically positive, while the anti-LKM test was still negative.
Analysis of liver tissue showed that immune infiltration was dominated by activated cytotoxic CD8 T cells with panlobular distribution. Enrichment of CD4 T cells, B cells, plasma cells, and bone marrow cells were also observed compared with the control. Compared with peripheral blood, intrahepatic infiltration showed enrichment of CD8 T cells with SARS-CoV-2 specificity.
It is worth noting that the T lymphocyte cluster in the liver tissue of patients is the richest among their immune cells, which differs from typical autoimmune hepatitis, and the researchers found that there is a wider infiltration of immune cells around the portal vein of patients.
The researchers finally ...
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