What is Hepatitis B?

Hepatitis B virus (HBV) is a pathogen that causes hepatitis B (Hepatitis B for short) and belongs to the family Hepadnaviridae. The cause of human infection is orthohepadnavirus. HBV infection is a global public health problem. With the production and investment of genetically engineered vaccines, the spread of hepatitis B vaccine has increased year by year, and the infection rate has shown a downward trend.

Basic Information

Chinese name

Hepatitis B virus

Foreign name

hepatitis B virus

Abbreviation

HBV

Common detection

HBV antigen and antibody detection

1. Morphology and structure Under the electron microscope, hepatitis B virus can take on three types of particle structure: large spherical particles with a diameter of about 42 nm, small spherical particles with a diameter of about 22 nm, and tubular particles. Large spherical particles (Dane particles) are complete virus particles, consisting of an envelope and a nucleocapsid. The envelope contains HBsAg, glycoprotein, and cell fat. The core particles contain core protein (HBcAg) and circular double-stranded HBV-DNA. And HBV-DNA polymerase, which is the complete form of the virus, is infectious. Both small spherical particles and tubular particles are composed of the same lipoproteins as the virus envelope. The former are mainly hollow particles formed by HBsAg. They do not contain DNA and DNA polymerase and are not contagious. The latter are formed by the polymerization of small spherical particles in series. Same as small spherical particles.
2. The virus life cycle HBV adheres to the surface of liver cells through low-affinity receptors (such as heparan sulfate, proteoglycan, etc.), and then mediates cell endocytosis of the virus through the preS1 region of the large envelope protein and virus receptors. effect. Sodium ion-taurocholic acid transport peptide (NTCP) is an important receptor that mediates HBV entry into cells and establishes infection. The fusion of endocytosis virus envelope and body swallow membrane releases the capsid into the cytoplasm and the capsid is transported. The viral genomic rcDNA into the nuclear pore complex is released into the nucleus. In the nucleus, rcDNA may be converted into covalently closed circular DNA (cccDNA) by the cell's DNA replication mechanism. cccDNA has a high degree of stability and can be maintained in the nucleus for months to years. This is the root cause of the virus rebound after antiviral treatment. Therefore, clearing cccDNA is of decisive significance for the eradication of hepatitis B. The virus uses cccDNA to transcribe 3.5 kb, 2.4 kb, 2.1 kb, and about 0.8 kb mRNA, of which 3.5 kb is pregenomic RNA (pgRNA), which can reverse transcribe genomic DNA and serve as a template for encoding viral core proteins and polymerase proteins After synthesis, HBsAg is polymerized in the rough endoplasmic reticulum and transported to the anterior cavity of the Golgi apparatus to package the core particles. The assembled HBV particles and subviral particles are transported to the Golgi apparatus for glycosylation of HBsAg. Finally, The budding method secretes intact virus particles out of the host cell to complete the life cycle. ^[1]

1. Sources of infection Acute hepatitis B patients, chronic hepatitis B patients, and carriers of hepatitis B virus are the main sources of infection. Hepatitis B virus infection is contagious in the blood regardless of the incubation period, acute phase or chronic phase. HBsAg positive for more than 6 months, no signs of hepatitis, liver function and other tests showed normal, serum ALT and AST are in the normal range, liver tissue examination showed no obvious abnormal symptoms called hepatitis B virus carriers . Chronic patients and carriers of viruses are the most important source of infection, and their infectivity is directly proportional to the virus replication or the hepatitis B virus DNA content in body fluids.
2. Transmission route The main transmission route of HBV is blood transmission (transfusion and blood products). The second is mother-to-child transmission, that is, newborns are infected by mothers with hepatitis B virus before and after childbirth. Breastfeeding can also cause mother-to-child transmission. This transmission path accounts for a large proportion in China. Chronic hepatitis B patients, 40% to 50% of patients are from mother-to-child transmission. The third is close contact transmission, such as transmission of virus through semen and vaginal discharge. The fourth is iatrogenic transmission, such as incomplete disinfection and unsafe injection.
(1) Transmission of blood and blood products: HBV exists in the blood in large quantities, and very small amounts of blood or blood products containing viruses can cause infections. In addition to blood transfusion, hemodialysis and organ transplantation can be transmitted.
(2) Vertical transmission from mother to child: mainly refers to intrauterine infection, perinatal transmission and postpartum transmission. Mothers carrying HBV can infect the fetus through blood flow.
(3) Close contact transmission: At present, it has been confirmed that saliva, sweat, vaginal secretions, semen, breast milk and other body fluids contain hepatitis B virus. Close life contact, especially sexual contact transmission is a common mode of transmission.
(4) Iatrogenic transmission: In medical or preventive work, the virus has been artificially transmitted due to failure to strictly follow rules and regulations and operating procedures, including the use of contaminated or poorly disinfected needles, needles, blood collection devices, etc.
3. Pathogenic mechanism The degree of liver cell damage is related to the strength of the body's immune response. There are several mechanisms by which HBV causes immune pathological damage.
(1) Low immune response caused by virus: When HBV is infected, the humoral antibody response to outer membrane antigens is beneficial to remove virus particles in the blood, and the cellular immune response to nucleocapsid and replicase antigens also clears the virus and damages liver cells. Most adults with normal immune function can clear the virus through the coordination of natural immunity and adaptive immune response after HBV infection, and produce HBV antibodies. If the virus cannot be effectively removed, such as low immune function or suppression, it will lead to continuous infection and It replicates in liver cells and forms a chronic infection. HBV can also inhibit the body's immune function after being infected with the human body. Those with low immune function cannot effectively clear the virus, making the infection prolonged and chronic. The immune response to viral antigens is associated with viral elimination and pathogenic mechanisms.
(2) Virus mutation produces drug resistance: The reason for persistent HBV infection is usually that the body's immune response to the virus antigen is low, which is often caused by immune escape after virus mutation. The virus can escape the body's specific immune response through this mechanism to make the infection into Chronic. The reason for the high variability of HBV is that the virus has a process of reverse transcription and replication, and RNA polymerase and reverse transcriptase lack correction function and are prone to errors. HBV is susceptible to mutation due to human immune pressure and the effects of anti-HBV drugs during the infection process. After HBV mutation, it can cause the virus to be difficult to remove and cause drug resistance, reducing the efficacy of antiviral treatment. The S gene mutation can cause HBsAg-negative HBV mutant strain infection, and "diagnostic escape" occurs. Prec / c region gene mutations hinder HBeAg synthesis, and patients are HBeAg negative, but their virus replication is not affected, so HBV DNA can be detected, even with high viral load; mutations in P region genes can directly affect antiviral treatment effect.
(3) Antibody-mediated immunopathological damage: Specific antibodies such as HBsAb, PreS1-Ab, and PreS2-Ab in the serum after HBV infection can directly clear the free virus in the blood circulation, but the immune complex formed by the antigen antibody can be deposited in the kidney Glomerular basement membrane, joint synovial sac, etc. activate complement and cause type hypersensitivity. Immune complexes can also be deposited in liver cells, causing hepatic capillary embolism, leading to acute liver necrosis, manifested as severe hepatitis. HBV infection can expose liver-specific lipoprotein antigens and induce the body to produce autoantibodies as autoantigens, which can damage liver cells through direct and indirect effects.
(4) Cell-mediated immune pathological damage: Immune cells play a direct role in killing target cells by recognizing HLA-I molecules and viral antigens on the cell membrane. Cellular immunity is an important factor for the complete removal of the virus, but it is a double-edged sword for the body. Excessive cellular immune response can cause large areas of liver cell damage and lead to severe hepatitis, but low cellular immune function cannot effectively remove the virus. Easy to cause chronic infection.

1. HBV antigen, antibody detection surface antigen (HBsAg), surface antibody (anti-HBs), antigen (HBeAg), antibody (anti-HBe) and core antibody (anti-HBc) are called five items of hepatitis B, which are commonly used HBV infection The detection index can reflect the HBV level of the subject and the body's response, and roughly evaluate the virus level. The five tests for hepatitis B are divided into qualitative and quantitative tests. Qualitative tests can only provide negative or positive results. Quantitative tests can provide accurate values of various indicators. It is more important for monitoring, treatment evaluation and prognosis of hepatitis B patients. Significance, dynamic monitoring can be used as a basis for clinicians to formulate treatment plans. In addition to the above five items, anti-HBc-IgM, PreS1 and PreS2, PreS1-Ab, and PreS2-Ab are also gradually applied in the clinic as indicators of HBV infection, replication, or clearance.
2. HBV DNA test The five tests of HBV cannot be used as an indicator to determine whether the virus is replicated, and DNA detection is sensitive to low levels of HBV virus in the body by amplifying the viral nucleic acid, which is a common method to judge the virus replication. DNA is the most direct, specific and highly sensitive indicator of hepatitis B virus infection. HBV-DNA is positive, which indicates that HBV is replicative and infectious. Higher HBV-DNA indicates more virus replication and greater infectivity. The continuous replication of hepatitis B virus is the root cause of hepatitis B. The treatment of HBV is mainly antiviral therapy. The fundamental purpose is to inhibit viral replication and promote the negative conversion of hepatitis B virus DNA. DNA testing also plays a very important role in the diagnosis of HBV and the evaluation of HBV treatment effects. It can understand the number of viruses in the body, the level of replication, infectivity, drug treatment effects, and formulate treatment strategies. It is also the only indicator that can help confirm the diagnosis. Laboratory testing indicators of sexual HBV infection and occult chronic HBV.

Hepatitis B vaccination is a necessary means to effectively control the spread of HBV. At present, China implements compulsory newborn immunization and vaccinates against hepatitis B as soon as it is born. The protective effect of antibody responders after vaccination generally lasts at least 12 years. Anti-HBs can be monitored in high-risk groups, and immunization should be strengthened if necessary. After accidental contact with the blood and body fluids of HBV-infected persons, five items of hepatitis B should be tested immediately. Those with anti-HBs <10mU / ml or unknown anti-HBs levels should be injected with HBIG200 400U immediately to neutralize the virus. Patients with acute or chronic HBV infection should report to the local Center for Disease Control and Prevention (CDC) in a timely manner in accordance with the Law of the People's Republic of China on Infectious Disease Prevention and Control, and indicate whether it is acute hepatitis B or chronic hepatitis B. ^[2]

On April 26, 2019, Deng Hongkui's research group at Peking University, Lu Shichun's research group at the General Hospital of the Chinese People's Liberation Army, and Yuan Zhenghong's research group at Fudan University published in the journal Science entitled Long-term function of primary human liver cells in vitro. "Sexual maintenance" research paper, for the first time, demonstrated that the use of chemical small molecules to regulate cell signaling pathways to achieve long-term maintenance of functional cells in vitro, and confirmed that this liver cell supports hepatitis B virus (HBV) and hepatitis C virus (HCV) in vitro The long-term persistent infection provides a possibility for the large-scale preparation of functional mature cells and their applications. ^[4]