Hepatitis B

　　First, the cause of the disease

　　1, Hepatitis B virus (HBV) is a spherical particle (Dane particle) with a diameter of 42-47nm, consisting of the outer shell and core. The outer shell contains many small spherical particles and only contains viral surface antigen (HBsAg), while the core contains circular double-stranded deoxyribonucleic acid (DNA), DNA polymerase, core antigen (HBcAg), and e antigen (HBeAg). The positive strand of the double-stranded DNA is short and incomplete, only 50% of the length of the negative strand, without open reading frames, and cannot encode proteins. The negative strand is complete and of constant length, about 3200 nucleotides in length, with 4 large open reading frames that can encode all viral proteins:

　　2, In the serum of HBV infected individuals, there are three different morphological virus particles, namely, spherical particles (diameter 22nm), tubular particles (diameter 22nm, length 100-1000nm), and Dane particles (diameter 42nm). The first two are excess HBV capsid proteins and incomplete or hollow particles, which are non-infectious. Only Dane particles replicate in liver cells and are infectious. Chimpanzees and rhesus monkeys are susceptible animals. HBV can grow in human renal and monkey renal cells, and human amniotic cells, and HBcAg can be detected from the above tissue culture medium, and it can cause cytopathic changes.

　　3, The resistance of HBV is strong, it can be inactivated by boiling for 30 minutes at 121°C, high-pressure steam for 15 minutes at 160°C, dry heat for 2 hours at 160°C, ethylene oxide at 1.6g/L for 45 minutes, sodium dichloroisocyanurate at 0.5% for 30 minutes, iodophor at 0.5% for 10 minutes, 2% aldehyde, and 0.5% peracetic acid for 7 minutes. Alcohols, quaternary ammonium salts, and chlorhexidine are not easily inactivated, and UV radiation for 30 minutes can kill HBV.

　　4, The subtypes of HBsAg and their significance: The group antigen determinant 'a' of HBsAg is common, while subtypes d and y, w and r are allelic, thus forming 4 main subtypes: adw, adr, ayw, and ayr. The W subtype can be further divided into W1, W2, W3, and W4. The distribution of HBsAg subtypes varies with geography, time, and ethnicity. The Han nationality in China is mainlyadr, followed by adw; ethnic minorities are mostly ayw, with ayr being rare. Application of subtype monoclonal antibodies has proven that d and y, w and r can coexist on the same antigen particle, forming complex subtypes such as adwr, aywr, adyw, or adyr. Although there is some cross-immunity between different HBsAg subtypes due to the group antigen determinant 'a', this cross-immunity is not complete.

　　The pathogenesis of the disease

　　1. The reason for the persistence of hepatitis virus infection is the low immune response to viral antigens, often due to immune escape after viral variation; neonatal immune tolerance plays an important role in the persistence of HBV infection.

　　2. Intrahepatic T cells: A large number of sensitized lymphocytes enter the liver in patients with CHB (Chronic Hepatitis B), and peripheral blood can only partially reflect the immune process occurring in the liver. Compared with patients without replication, the ratio of CD4/CD8 cells in the liver is significantly higher, indicating that the original site of helper-inductive CD4T cells may be activated by HBcAg and positively regulate the cytotoxic activity of CD8CTL. Approximately 70% of the Th cell clones isolated from active lesions are Th1 cells; while only 4% in PBMCs. The higher the density of Th1 cells in the CD4 cell population of the intrahepatic compartments, the higher the level of IFNγ produced, and the stronger the cytotoxic activity. The antigenic stimulation in the inflammatory environment of the liver may be conducive to the amplification of these cells, and Th1 cells participate in the liver cell injury mechanism of CHB.

　　3. Antigen-specific recognition: The initiation of a specific immune response is the recognition of target antigens by the T cell receptor complex. The T cell receptor complex (the complex of TCR on the lymphocyte membrane and CD3) also includes antigens on the surface of antigen-presenting cells or target cells and MHC determinants. The nucleocapsid protein epitope of HBV nucleocapsid antigen is only processed intracellularly, a small segment of oligopeptide (epitope peptide) consisting of 8 to 16 amino acids. The recognition site of CD4T cells is roughly located at the AAl-25 and AA61-85 epitopes of HBc/eAg peptide; the sequence region recognized by CD8CTL is not fully defined. T cells of different ethnic groups and different MHC types in different subpopulations of infected individuals have different recognition epitopes on the amino acid sequence of the nucleocapsid antigen. IgG-anti-HBc can partially mask the expression of HBcAg, and anti-HBc inhibits the recognition of HBV target antigens by CTLs, which is one of the factors that cause the persistence of HBV infection. Anti-HBc can also inhibit the cytotoxic effect on liver cells, and the same effect can occur with the anti-HBc passively transferred from the mother.

　　4. HLA (HLA antigen) restriction: The antigenic oligopeptide/HLA-Ⅱ complex presented by APC (antigen-presenting cell) can directly bind to the β2 structural domain of the CD4T cell CD4/HLA-Ⅱ molecule, thereby defining the specificity of the interaction between effector and target cells. The cell membrane of patients with active liver disease has a strong HLA-I expression, which can more effectively provide nuclear shell oligopeptides to T cells.

　　5, Similarly, antigenic peptides in APC bind to HLA-Ⅱ to form complexes, which are presented on the cell surface. Th cells use their surface CD4 molecules to detect HLA-Ⅱ on the surface of APC and use their TCR to detect complementary antigenic peptides in the groove. This is the recognition process of CD4 Th cells.

　　6, The binding between TCR and peptide/HLA complex is unstable. CD4 molecules must bind to the β2 region of HLA-Ⅱ, and CD8 molecules must bind to the α3 region of HLA-I to form a three-dimensional structure to maintain stability. The necessary contact time between TCR and the complex, in addition, these cells all produce cell adhesion molecules, which strengthen the interaction between cells.

　　7, The immunogenetic basis expressed by MHC (major histocompatibility complex) is an important factor limiting the development of HBV infection, which can explain the racial differences in susceptibility to HBV. There have been many reports on the correlation between HLA typing and clinical course in HBV carriers, but there is no consensus. HLA typing positively associated with the chronic active lesion of HBV infection includes A3-B35, A29, A2, B8, B35, DR3, DR7, and negatively associated include B5, B8, DQwl, DR2, and DR5.

　　8, Cytokines: Cytokines transmit immune information between cells, forming an immune regulatory cytokine network among them. Through this network, cell-mediated immune responses are carried out. During acute hepatitis, IFN is induced locally, and infected hepatocytes release IFN into the surrounding medium, causing adjacent hepatocytes to be in an antiviral state. During chronic hepatitis, cytokines released in situ by infiltrating mononuclear cells or other non-parenchymal cells play a role in immune responses, cell proliferation, and fibrosis.

　　1, Hepatic encephalopathy is caused by severe liver disease and is a syndrome of central nervous system dysfunction based on metabolic disorders, with changes in consciousness and coma as the main manifestations. The pathogenesis of hepatic encephalopathy has not been fully elucidated, and it is generally believed to be related to the following factors.

　　2, Hemorrhage is a common and severe complication of severe hepatitis, and one of the important causes of patient death. The mechanism of hemorrhage in severe hepatitis is multifaceted. When the liver function is severely damaged, coagulation factors decrease, such as the decrease in coagulation factor I, II, V, VII, IX, and X, the synthesis of which is reduced; the number of platelets decreases, and their morphology changes (decreased volume, pseudopodia formation, vacuolation, and blurred serosa); capillary endothelial cell injury, increased fragility; elevated serum TNF and endotoxemia lead to multi-system damage, renal failure, DIC, and acute gastric mucosal changes; portal hypertension causes congestion of visceral capillaries, vascular dilation, increased permeability, plasma extravasation, mucosal edema, erosion, and ulcers, etc.; the rupture of esophageal-gastric varices is also one of the causes of hemorrhage in chronic severe hepatitis.

　　3. Hepatorenal syndrome (HRS) HRS is a severe complication in the late stage of severe hepatitis. The renal tissue of patients is completely normal or only slightly damaged. If liver disease can be reversed, renal function can improve. If the kidneys of patients who died of HRS are transplanted into chronic uremic patients, or normal liver is transplanted into HRS patients, it can quickly restore renal function in different patients. The incidence of HRS in severe hepatitis is about 30% to 50%, with a very high mortality rate. Most patients die within a week after oliguria or anuria due to gastrointestinal bleeding, hepatic encephalopathy, or direct death from HRS. The pathogenesis of HRS is very complex, including changes in renal hemodynamics, renal vessel spasm, and widespread renal cortical ischemia as the basic factors.

　　3. Infection with severe hepatitis leads to decreased immune function, an increased chance of co-infection, and severe infection can further damage the liver, promoting the occurrence of liver failure.

　　1. General symptoms

　　The liver affects the whole body. Due to liver dysfunction, hepatitis B patients often feel fatigue, lack of energy, edema of the lower limbs or the whole body, easy to fatigue, lack of vitality, insomnia, and frequent dreams, etc. Some people may also have hepatitis symptoms similar to a cold.

　　2. Gastrointestinal symptoms

　　The liver affects the whole body. Due to liver dysfunction, hepatitis B patients often feel fatigue, lack of energy, edema of the lower limbs or the whole body, easy to fatigue, lack of vitality, insomnia, and frequent dreams, etc. Some people may also have hepatitis symptoms similar to a cold.

　　3. Jaundice

　　The liver is the central organ for bilirubin metabolism. An increase in bilirubin concentration in the blood of hepatitis B patients can cause jaundice, yellowing of the skin and urine, and urine with a concentrated tea color, etc.

　　4. Liver pain

　　The liver generally does not feel pain, but there are pain receptors distributed on the liver capsule surface. When hepatitis B worsens, patients may experience discomfort or dull pain in the upper right abdomen and right hypochondrium.

　　5. Liver and spleen enlargement

　　Due to inflammation, congestion, edema, and bile stasis, hepatitis B patients often have liver enlargement and other symptoms.

　　6. Palm manifestations

　　Many hepatitis B patients will have symptoms such as liver palms. The palm surface of hepatitis B patients will become congestive and red, and there will be obvious tenderness on the second metacarpophalangeal joint of the thumb and index finger, etc.

　　7. Skin manifestations

　　Many chronic hepatitis patients, especially liver cirrhosis patients, have dark or sallow complexions, known as liver disease facial features, which may be symptoms of hepatitis B caused by endocrine disorders. At the same time, hepatitis B patients may also have symptoms such as spider angiomas on their skin.

　　1. For hepatitis B patients, there is no fixed isolation period. For inpatients, they can be discharged as long as the liver function is stable. HBsAg carriers in the convalescent period should be followed up regularly. For personnel in direct contact with food and caregivers, health check-ups should be conducted annually. Patients in the acute phase should maintain normalcy for half a year after recovery, HBsAg-negative patients can resume their original work, chronic patients should be transferred away from direct contact with food and childcare work, and for suspected cases that have not been diagnosed, they should suspend their original work and strictly screen blood donors according to national regulations.

　　2. Interrupt the route of transmission: Strengthen health education and management, prevent iatrogenic transmission, ensure that each person uses a needle and syringe, and implement disinfection. Promote the use of disposable syringes, thoroughly disinfect items contaminated with blood, and strengthen the management of blood products.

　　3. Protection for susceptible populations: Hepatitis B vaccine is highly effective and safe, and can be administered according to the 0, 1, 6-month schedule, intramuscularly in the deltoid muscle, with a blood-derived vaccine of 10-30μg per dose, and a recombinant vaccine of 5-10μg. The protective effect of anti-HBs is positively correlated with the titer, and it is generally considered that a titer of >10U/L has a protective effect. For hemodialysis patients and other immunocompromised individuals, the dose or frequency of vaccination should be increased. Hepatitis B immunoglobulin (HBIg) is mainly used for newborns of HBeAg-positive mothers and can be used in combination with the hepatitis B vaccine. Most HBIg produced in China is U/ml, and the dosage should be 0.075-0.2ml/kg.

　　1. Liver function tests:Including bilirubin, turmeric turbidity test, AST, ALT, A/G, prothrombin time, serum protein electrophoresis, etc.

　　2. Specific serological etiological examination:Including HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HBcIgM. If conditions permit, HBV-DNA, DNA-p, Pre-S1, Pre-S2, etc. can be detected. In situ hybridization technology is used to detect HBV-DNA in the liver.

　　I. Diet for Acute Hepatitis B

　　1. In the early stage of acute hepatitis, patients often have obvious symptoms such as nausea, vomiting, and poor appetite. At this time, the food consumed by the patient often cannot meet the needs of the body. Therefore, during this stage, it is advisable to consume easily digestible and light foods such as noodles and congee, with moderate amounts of vegetables and fruits, and to eat in small and frequent meals. The diet should be based on the amount and frequency that the patient feels comfortable with, and it is not advisable to force the patient to eat more.

　　2. During the recovery period of acute hepatitis, as the symptoms of nausea and vomiting disappear and appetite improves significantly, it is appropriate to increase the intake of protein and unsaturated fatty acids. Protein sources can include soy products, milk, chicken, and freshwater fish with low fat content, and unsaturated fatty acids mainly come from vegetable oils. The amount of food should be gradually increased and the process should be gradual. It is particularly emphasized that excessive intake of sucrose and glucose during acute hepatitis, especially in the recovery period, can easily cause fatty degeneration of liver cells, which is反而不利于 hepatitis recovery.

　　II. Diet for Chronic Hepatitis B

　　1. Sufficient protein supply can maintain nitrogen balance, improve liver function, and benefit the repair and regeneration of liver cell damage.

　　2. Provide an appropriate amount of carbohydrates: Carbohydrates should account for 50-70% of the total calorie intake. Adequate carbohydrates can not only ensure the total calorie supply for patients with chronic hepatitis but also reduce the decomposition of body tissue proteins, promote the liver's utilization of amino acids, increase glycogen reserves, and enhance the detoxification ability of liver cells.

　　3. Appropriate restriction of fat intake: Fat is one of the three major nutrients, and the unsaturated fatty acids it provides are essential nutrients for the body, which cannot be replaced by other foods. Therefore, it is not necessary to restrict it too strictly. Additionally, the intake of an appropriate amount of fat is beneficial for the absorption of fat-soluble vitamins (such as vitamin A, E, K, etc.). Due to the decreased appetite in chronic hepatitis patients, often accompanied by gallbladder diseases, fat intake is often insufficient. Chronic hepatitis patients need to consume an appropriate amount of fat-containing foods, but it is not appropriate to restrict fat excessively. The daily fat supply should generally be around 40-60g, or about 25% of the total daily energy intake. Chronic hepatitis patients with fatty liver, hyperlipidemia, or acute attacks of cholecystitis should limit fat intake.

　　4. Supplementing an appropriate amount of vitamins and minerals: Vitamins play an important role in detoxification, regeneration, and enhancing immunity of liver cells. Vitamins are often used as adjuvant treatment for chronic hepatitis. The main method of supplementing vitamins is through food, and it is still beneficial to supplement vitamin preparations in cases of insufficient intake. Chronic hepatitis patients are prone to calcium deficiency and osteoporosis, so it is necessary to persistently drink milk or take calcium supplements appropriately.

　　5. Abstain from alcohol and avoid the intake of substances harmful to the liver: Ethanol can cause damage to liver cells, and the detoxification ability of the liver in chronic hepatitis patients decreases. Even a small amount of alcohol can exacerbate liver cell damage, leading to worsening liver disease. Therefore, hepatitis patients should abstain from alcohol.

　　Different treatment measures should be taken according to the clinical type and different types of etiology. The general principle is: mainly based on appropriate rest and a reasonable diet, with selective drug use as an adjunct. It is necessary to avoid alcohol, prevent overexertion, and avoid the use of liver-damaging drugs. Drug use should be kept simple rather than complicated.
　　1. Treatment for acute hepatitis
　　(1) Early strict bed rest is most important. As symptoms improve, gradually increase activity levels, following the principle of not feeling tired. Treatment can be terminated when symptoms disappear, isolation is completed, and liver function is normal, allowing discharge. After 1-3 months of rest, gradually resume work.
　　(2) Diet should be tailored to the patient's taste, and easy-to-digest light foods are recommended. It should contain a variety of vitamins, have sufficient calories, and an appropriate amount of protein. Fats should not be restricted too strictly.
　　(3) The most effective treatment for acute hepatitis B is antiviral therapy, in addition to adequate rest and a reasonable diet. Appropriate medication should be given according to different conditions, while avoiding alcohol consumption, the use of hepatotoxic drugs, and other factors harmful to the liver.
　　(4) The treatment of traditional Chinese medicine should be adapted to local conditions, using herbal medicine or herbal formulae for differential treatment. The treatment of acute hepatitis should focus on clearing heat and dampness, dispersing turbidity, and regulating Qi and blood circulation. For those with heat predominant symptoms, Yin Chen Hao decoction, Zhizi Bai Pi decoction, or dragon bone, ban lan gen, jin qian cao, and jin yin hua can be used; for those with dampness predominant symptoms, Yin Chen Si Ling San and San Ren decoction can be used.
　　(5) Nutrition should be high in protein and moderate in calorie intake to prevent fatty liver. It is also not advisable to consume excessive amounts of sugar to avoid diabetes.
　　(6) Antiviral drug treatment ①α-Interferon (Interferon, IFNα): It can prevent the virus from replicating within the host liver cells and has immunomodulatory effects. However, the serum indicators of some cases may reverse after discontinuation of medication. Early, high-dose, long-term interferon therapy can improve efficacy. Side effects include fever, hypotension, nausea, diarrhea, muscle pain, fatigue, and may appear in the early stages of treatment, and temporary hair loss, granulocytopenia, thrombocytopenia, anemia, and other conditions may occur, but they can recover quickly after discontinuation of medication. ②Interferon inducers: Polyinosinic acid (polyriboinosine, PolyI:C) can block viral replication in the body by inducing interferon, but its ability to induce interferon is low. A new drug Amplige (PolyI:C·12U) has been synthesized recently, which is a interferon inducer stronger than polyriboinosine.
　　2. Treatment for chronic hepatitis
　　Improving the quality of life is the ultimate goal of hepatitis B treatment. As everyone knows, it is difficult to completely eliminate the hepatitis B virus. Whether interferon or nucleotide analogs can only inhibit the replication of the hepatitis B virus. After short-term treatment (≤1 year), the level of HBV-DNA in patients may rebound sharply after discontinuation of medication, leading to recurrence of hepatitis B. It is most忌讳 to stop taking antiviral drugs early, or to discontinue or change medication arbitrarily, which may cause the condition to worsen, ultimately resulting in poor efficacy and exacerbating the progression of the disease. Therefore, everyone must adhere to long-term and standardized medication during treatment.
　　3. Treatment for severe hepatitis
　　Early detection and treatment has the possibility of recovery, but a considerable number of patients have poor prognosis. Patients should absolutely stay in bed, avoid and remove triggers that induce hepatic coma, prevent and control infection, timely treat hemorrhage, and strengthen symptomatic supportive therapy. Those who have the conditions should consider liver transplantation surgery.
　　4. Treatment for asymptomatic HBsAg carriers
　　For those with HBV replication indicators positive, antiviral drug treatment is applicable, and α-IFN is the first choice.