Autoimmune hepatitis is a diffuse and progressive inflammatory disease of the liver, which is reflected by autoimmune receptors. Its medical characteristics are different degrees of serum protein transaminase increase, high γ immunoglobulin urine and autoantibody positive. Its pathological feature is page hepatitis, which mainly consists of lymph node cells and plasma cells. In severe cases, it can rapidly develop into cirrhosis, ascites and liver failure.
The above research was published in JournalofHepatology, an international academic journal of hepatology industry, on April 2 1 day. The creators include the Medical College of Freiburg University, the Institute of Pathology of technical university of munich Medical College, and the German Cancer Society. Journal of Hepatology (202 1) has an impact factor of 25.083, ranking first in the field of gastrointestinal and liver diseases.
COVID-19 vaccine is very important to resist the COVID-19 virus. COVID-19 mRNA vaccine (BNT16B2) developed by Pfizer /BioNTech is one of the vaccines with the largest number of vaccinations in the world. In particular, compared with vaccines developed by traditional technology platforms such as eradication vaccine, mRNA vaccine only "made its debut" in coronavirus pneumonia-19 epidemic, and scientific and technological circles around the world are still studying its main performance in the real world.
This clinical study from Germany published the bimodal incidence of acute hepatitis after two doses of Pfizer mRNA vaccine. This male patient is 52 years old in 2022 and has no other medical history except hypothyroidism.
He developed neonatal jaundice 10 day after the first dose of mRNA vaccine, and liver function test (LFT) showed subacute mixed hepatocyte/cholestatic hepatitis. 25 days after inoculation, the patient was hospitalized for treatment.
465438+ 0 days after the first vaccination, the patient was vaccinated with the second dose of BNT16B2 vaccine. Twenty days after the second inoculation, the patient developed fatigue, nausea, vomiting and other symptoms, and the test showed a subacute mixed hepatitis attack. 26 days after the second vaccination, the patient was transferred to a tertiary medical center for treatment.
What is the cause of hepatitis? The researchers carried out serological and polymerase chain reaction (PCR) tests on the patients, and it was very possible to exclude hepatitis A, hepatitis B, hepatitis C or hepatitis E virus, cytomegalovirus (CMV) and Epstein-Barr virus infection.
Autoimmune serological tests showed that the patient had mild hyperimmunoglobulin urine, and the critical values of anti-nuclear antibody (ANA), anti-membrane protein M2 antigen (AMA-M2) and anti-sarcoplasmic reticulum antigen were all positive, while LKM antibody was negative. Then, the liver biopsy was performed on the patient, and it was found that the hepatitis symptoms of the patient included mild and moderate lymph node plasma cell infiltration, lobular atrophy and apoptosis.
Scholars' research shows that the symptoms of this 52-year-old patient are consistent with the main manifestations of his autoimmune diseases. The patient received 9 mg of budesonide daily. Budesonide is a highly effective and partially anti-infective hormone drug. Collectable data show that these drugs can improve the reliability of epidermal cells, sarcoplasmic reticulum cells and lysosomal membranes, inhibit immune response and reduce antigen production. Within a few weeks after treatment, the patient's liver enzyme level decreased and gradually improved.
However, the patient relapsed after 39 days of treatment, and scholars showed that the hepatitis attack was caused by the reduction of budesonide hormone treatment. So the drug was treated again, and the continuous liver function examination showed that after eight weeks of continuous treatment, the patient returned to normal, and there was no obvious fluctuation of COVID-19 S protein specific antibody in the patient.
In addition, researchers also saw the infiltration of T cells and B lymph node cells, macrophages, granulocytes and plasma cells in patients' liver organs. Scholars have shown that they have observed that the immune cells in the liver of this 52-year-old patient are 5.3 times higher than those in the liver of an unaffected patient.
Especially, T-lymph node cell cluster (CD8) in patients' liver is the most abundant in their immune cells, which is different from typical autoimmune diseases. At the same time, patients' B cells and plasma cells are relatively low, while classic autoimmune diseases have more B cells and plasma cells. For the data mining technology of liver with different immune cell subsets, scholars have found that there are more common immune cell infiltration around portal vein. Although patients' B cells and plasma cells mainly gather in the area around the portal vein, (CD8)T lymph node cells are lobulated. It is particularly noteworthy that the cytotoxic side effect (CD8)T cells in patients are relatively highly accumulated, while the levels of other cells expressing granzyme B remain unchanged.
According to flow cytometry, scholars analyzed the types of (CD8)T cells in and around the liver in detail. The patient's intrahepatic (CD8)T cell bank showed the aggregation of dysphonia markers (CD38) and institutional retention markers (CD 103, CD69 and CXC motif chemokine protein kinase 6[CXCR6]). (CD8)T cells in blood cells also express CD38. Scholars' research shows that, interestingly, the expression of CD38 in patients without hepatitis symptoms after vaccination (75.9%) is significantly higher than that in normal control group (65,438+05.4%). Compared with blood cells, the aggregation of COVID-19 nonspecific (CD8)T lymph node cells in patients' liver (CD8)T cells is 3.4 times that of blood cells.
The evolution rate of S- nonspecific (CD8)T lymphocyte in patients' blood cells is 65438 00.2 times higher than that of Epstein-Barr virus nonspecific T lymphocyte epitope. The level of CD38 decreased after budesonide treatment. It is well known that when budesonide attacks during treatment, the expression of CD38 on nonspecific (CD8)T cells, which is a marker of COVID-19's protein and other cytotoxic side effects, rises again, but it is recovered after treatment with systemic immune enhancer.
According to scientific research, the symptoms of this 52-year-old patient are different from typical autoimmune diseases, which are usually related to the increase of immunoglobulin in peripheral population, the invasion of plasma cells and prominent page hepatitis. In this clinical medical example, although the aggregation of peripheral human immunoglobulin and intrahepatic B cells and plasma cells increased slightly, a more obvious correlation was observed in the degree of cytotoxic side effect (CD8)T cells. T cells containing cytotoxic side effect (CD8) with nonspecific reactivity of COVID-19 caused by vaccine are relatively highly aggregated in patients' liver, so they become a more aggregated immune cell group in patients' liver. Especially, the peripheral activation of COVID-19's S- nonspecific (CD8)T cells is related to the severity of hepatitis and the clinical medical condition after the introduction of autoimmune diseases.
According to the cellular immune system, the elite team of scientific research thinks that vaccination with BNT16B2 vaccine is likely to cause hepatitis symptoms in immune recipients. This result suggests that T cells are an important class of highly pathogenic immune cells related to this kind of vaccine immune diseases, and this kind of hepatitis is a new type of papillomavirus with autoimmune diseases.