Hepatitis B is caused by what is it?

Hepatitis B virus (HBV) for the single-minded hepatotropic virus, nucleic acid hybridization technology in recent years due to progress in the cells of the liver and other organs can be detected HBV-DNA. The liver through the Beijing duck hepatitis B virus in a test study provides evidence of extrahepatic cell replication. Human HBV may also be copied in extrahepatic cells, needs further investigation. HBV-infected serum by electron microscopy there are three kinds of virus-like particles: ① Dane particles (HBV particles), coat protein of HBsAg, the core containing the HBV-DNA and HBVDNAp (DNA-polymerase), HBcAg, HBeAg; ② small spherical particles; ③ tube particles. After the two were in excess of HBV replication coat of the virus (HBsAg), does not contain nucleic acid. HBV genome (HBV-DNA) from the ring structure of double-stranded DNA is not entirely composed of, containing 3200 nucleotides. Because of its smaller host range in vitro cell culture isolated virus has yet to succeed. In recent years, along with the application of molecular cloning techniques and in vitro cultured cell lines transfected with the success of the HBV replication process has been further understood. HBV-DNA into a negative chain (long chain), and positive-strand (short chains) formed. Its negative strand has four open reading frames (Open Reading Frame, ORF): ① S gene region from the S gene, pre-S2 (pre-S2) gene, pre-S1 (pre-S1) genetic make-up. Respectively, encoding HBsAg, pre-S, pre-S1 and a number of polymerized human serum albumin receptor (PHSA-R); ② C gene region from pre-C gene and C genetic makeup. Respectively, encoding HBeAg and HBcAg; ③ P gene region encoding HBV-DNAp, and with reverse transcriptase; ④ X gene region, coding HBxAg, and activate the role of HBcAg gene. HBV replication HBV Although the double-stranded circular genomic DNA, but RNA replication process has the characteristics of retroviruses need to produce reverse transcriptase RNA / DNA intermediates, and then continue to replicate. The process as follows: ① by the virus and / or cell-derived DNA-p under the action of being an extension of the formation of the first chain of covalently closed circular DNA (Covalently Closed Circular DNA). ② this as a template, the role of the host liver enzymes transcribed into a replication intermediate. ③ longer use this as a template, through the role of reverse transcriptase to form a first-and second-generation DNA. This part of the double-stranded DNA cyclization, that is, the completion of HBV-DNA replication. HBV mutant studies because of HBV replication has its own particularity, that is, the process of mRNA reverse transcription intermediates, because of the lack of proofreading enzymes (Proofreading Engymes) likely to occur in HBV-DNA sequence variation. ① S gene mutations lead to changes and serum HBsAg subtype HBsAg resistance, HBV-DNA positive hepatitis B, making clinical diagnosis difficult. Some people vaccinated production of anti-hepatitis B vaccine-HBs, but still be HBV S-gene mutant infection, to avoid the host immune response. ② pre-C gene mutations in HBV infection and immunity and the pathogenesis of severe hepatitis. Is generally believed that hepatitis B patients with HBeAg seroconversion, anti-HBe turn-yang, said that the level of activity decreased HBV replication and clinical symptoms improved. However, some patients when HBeAg seroconversion, there are still virus replication and progressive disease development, in addition to detection of serum HBsAg and anti-HBe, the can be detected HBV-DNA, anti-HBcIgM, intrahepatic HBcAg positive, liver damage caused by the exclusion of other causes, suggesting changes and HBV related illness. Which is characterized by a natural ease is not easy, and often develop into cirrhosis of the liver, poor response to antiviral therapy. The study shows that the Department of such patients are infected with HBV pre-C mutant gene mutation. ③ P gene mutations in HBV replication can be induced reduced or stopped. ④ X gene mutation can HBxAg synthetic barriers. In recent years, found that some HBV infection has always been anti-HBc could not be determined; some recovery is also measured in patients with no anti-HBs, and even some patients were HBV-negative, but able to detect HBV-DNA, in the liver cells and liver cell membrane there HBcAg and HBsAg. This type of infection in chimpanzees in patients with hepatitis can cause the performance of the typical. Some scholars call it HBV2. In recent years, studies have shown that these patients with serum HBV-DNA sequence analysis, we found S Zone, C Zone, X area there are several point mutations, suggesting that the HBV mutant strain HBV2. Strains of HBV gene mutation causes of the virus to adapt to the environment and the resistance of its host cell immune response to an option that can occur in HBV natural infection, HBV vaccination, immunotherapy and interferon treatment, or begin the initial HBV infection namely, a mutant strain of HBV infection. Specific marker for diagnosis and its clinical significance is as follows: 1. HBsAg and anti-HBs HBsAg in serum HBV infection in HBsAg-positive is a sign. Itself antigenicity, non-infectious. However, HBsAg and HBV often coexist, it is considered to be one of the hallmarks of infectious. It should be noted, HBV-DNA can be played from the X gene region of destination and liver cells reverse integration, integration of gene expression after S-strong, continuously produce HBsAg, an integrated genome HBcAg was inhibited, did not express HBsAg, HBsAg, in which circumstances, even if HBV clearance from the body, but still managed to sustain positive for HBsAg, in theory, this HBsAg-positive blood is not infectious. Acute HBV infection, first appeared in serum HBsAg, the acute phase can be positive, to the recovery period may be decreased or negative in titer. Such as the continuing positive HBsAg for more than half a year, known as chronic HBsAg carriers (HBsAg asymptomatic carriers), sustainable positive for several years. Is generally believed that a disproportionate level of HBsAg titer and disease. With normal liver function, HBsAg titer higher liver lesions can be an important, if the HBsAg-negative and DNAp negative, indicating no important infectious. On the contrary, abnormal liver function, HBsAg titer is not high, the liver may have significant disease and, if part of the cirrhosis, liver cancer patients was HBsAg negative or low titer. Asymptomatic HBsAg carriers, or chronic active hepatitis B may have the same change in HBsAg titer do not represent the severity of illness, factoring this can not be HBsAg titer change as the severity and drug treatment to determine effectiveness indicators. Using immuno-electron microscopy and immunofluorescence in the cytoplasm of liver cells confirmed HBsAg, but negative for serum HBsAg, there is no precise explanation of its mechanisms. One of the reasons is what is known to use the RIA assay, the test sensitivity of 10-5, still can not measure the amount of the lowest infection (10-7), resulting in 10% false-negative, so the judgments of HBsAg in order to have positive diagnostic value, and negative HBV infection can not be excluded. In recent years, were found in serum HBV-negative, while in the white blood cells or liver cells detected HBV-DNA, except for determining or HBV infection can not simply whether HBsAg-positive should be combined with other signs to judge. HBsAg has 10 subtypes, exist between the various subtypes of incomplete cross-immunity. In recent years, studies have shown that monoclonal antibodies with subtype, d, and y, w and r determinants can coexist on the same viral antigen particles to form adwr, aywr, adyw and adyr composite subtype. The mechanism of ① the dual infection of different subtypes of the virus; ② a single subtype of virus infection, some HBV-DNA point mutation. Clinical manifestations of disease relapses, liver damage heavier, and therefore some of HBV infection in HBsAg-positive serum in the same time, anti-HBs positive. Anti-HBs is infected with HBV or arising after hepatitis B vaccination as a protective antibodies. Of anti-HBs after HBV infection in the first 6 to 23 weeks there, about 20% of the early stage of infection into the recovery in the disappearance of HBsAg after a few months to 1 year of anti-HBs. Anti-HBs positive that it has access to immunization. Quantitative detection of anti-HBs titer that the anti-HBs titer ≥ IUml expressed their protection. 2. Pre-S1, pre-S2, and pre-S 1.pre-S1, pre-S2 Both are indicators of HBV replication. 2. Anti-pre-S If the detection of anti-pre-S-positive that HBV is being or has been cleared. 3. HBcAg and anti-HBC HBcAg for the HBC replication target. In peripheral blood of non-dissociative HBcAg, when Dcne particles by detergent treatment, HBcAg can be released, so the general could not be determined in serum. Exist in the infected liver nuclei and liver homogenate. In recent years, that the HBcAg in the liver cells caused by the existence of the immune response leading to liver cell necrosis of the important target antigen, anti-HBc immune effects. Anti-HBc as a sign of HBV infection. Anti-HBc IgM-positive acute or recent HBV infection indicators, suggesting that the virus replication. On behalf of the acute phase of their titer, efficiency lowest on behalf of a chronic HBV infection or asymptomatic HBsAg carriers. Anti-HBc IgG is expressed as positive indicators of past HBV infection. Single anti-HBc positive, found in the following cases: ① HBV early recovery after acute infection (window period), HBsAg disappears, anti-HBs has not yet appeared. ②-HBs obtained after immunization disappear, or below the detection level. ③ HBsAg carriers, HBsAg at a level below detection. ④ anti-HBc passively transferred to the baby through the placenta from the mother. 4. HBeAg is an important indicator of HBV replication. Exist in the hepatitis B surface antigen-positive blood. HBsAg-negative and HBeAg-positive experience, the reasons are: ① the method is not sensitive detection of HBsAg; ② serum rheumatoid factor (RF) interference; ③ HBsAg and anti-HBs has been the formation of immune complexes, could not be determined HBsAg; ④ in disappearance of HBsAg or anti-HBs appears, there are still serum Dane particles, whose shell-HBs wrapped HBsAg was measured not HBsAg; ⑤ reagents and operation and other factors, can cause false-positive HBeAg. 5. HBV-DNA and DNA-p HBV-DNA positive is that the most reliable indicator of HBV replication. In recent years, polymerase chain reaction (PCR) in this in vitro DNA amplification technique, so that the sensitivity increase by 100 times (10FGfg/ml), can detect very small amount of the virus. HBV-DNA-p is the HBV core possess DNA-p, in the process of viral replication enzymes play a role reversal. DNA-p activity is complex defects that HBV an important indicator of vitality. HBV-DNA and DNA-p detection of HBV infection will help to determine the extent of viral replication and infectious sizes, more sensitive evaluation of the efficacy of antiviral drugs. In summary, HBV logo appears in order of HBsAg, HBeAg, anti-HBc-(anti-HBcIgM, anti-HBcIgG), anti-HBc, anti-HBs, simultaneous detection of the above may indicate the stage of HBV infection. The pathogenesis of hepatitis B is very complex and a lot of research data, but has not yet been fully clarified. At present that is not in liver cell injury in HBV replication in liver cells, the result, but by the T-cell mediated drug reaction. People are infected with HBV, may cause cellular immunity and humoral immune response and to stimulate their own immune response and immune regulation dysfunction. The immune response against hepatitis B clinical presentation and prognosis are important. 1. Acute hepatitis HBV infection when the immune function was normal, its cytotoxic T cells (Tc cells) attack on infected liver cells, liver cells from damage released into the blood of HBV, which were specific antibody binding, and interferon produce more, Er Zhi HBV is cleared, the condition improved after all cured. 2. Chronic active hepatitis Defects found in immune function and immune regulation disorders. HBV infection, due to Tc-cell function is abnormal, or the closure of part of the liver cell-specific antibodies target antigens and restricted cytotoxic T response to liver cell damage induced by some. Produce less interferon, HBV continuous replication. Lack of specific antibody formation, hepatocellular HBV repeatedly been penetrated, the formation of chronic infection. In addition, the liver cell membrane-specific lipoprotein (Lsp) due to the formation of self-antigen HBV infection, stimulate B cells to produce anti-Lsp (IgG type), in suppressing T-cells (Ts cells) activity decreased circumstances, the effect of autoimmune-induced ADCC damages liver cells. 3. Chronic persistent hepatitis and asymptomatic carriers of HBsAg When the immune function when infected with low HBV, can not produce an effective immune response to liver cell damage induced by mild or no liver cell damage occurs. In particular, HBeAg asymptomatic carriers, the lack of interferon, can not be rid of the virus, resulting in a long time to carry HBV. 4. Fulminant hepatitis The occurrence of acute fulminant hepatitis, due to the immune response is too strong in the short term T-cell response to the rapid destruction of a large number of toxic liver cells infected with HBV; or shortly the formation of large antigen-antibody complex, activating complement, induced hypersensitivity occurred there (Arthus reaction ), resulting in massive liver cell necrosis; the absorption of gut-derived endotoxin can be induced Schwartzman reaction, so that avascular necrosis of liver cells; to be α-tumor necrosis factor (TNF-α), IL-1 and leukotriene, etc. cell factor by mononuclear macrophages, promote liver cell injury. The pathogenesis of subacute severe hepatitis and acute hepatitis similar to, but progress more slowly. The pathogenesis of chronic severe hepatitis complicated, pending further study. The most obvious of liver lesions, diffuse in the entire liver. The basic lesion of liver cell degeneration, necrosis, inflammatory cell invasion, liver regeneration, fibrous tissue hyperplasia. 1. Acute hepatitis ① diffuse liver cell degeneration and cell swelling into a spherical (balloon-like change), a liver cell changes and eosinophilic eosinophilic corpuscles; ② points, or foci of hepatocyte necrosis; ③ regeneration, and mild periportal inflammatory cell infiltration. Icteric and non-jaundice is only different degrees of liver disease, the former may appear the phenomenon of intrahepatic cholestasis. 2. Chronic hepatitis ① chronic persistent hepatitis and acute hepatitis the same to a lesser extent, lobular sector plate full. ② chronic active hepatitis, acute hepatitis, compared with heavy, often piecemeal necrosis, community boards have been destroyed, or bridge-like necrosis. In severe cases, hepatic lobule is damaged, liver cells were irregular nodular hyperplasia, hepatic lobule and portal area with proliferation of collagen and fibrous tissue. 3. Fulminant hepatitis 1. Acute fulminant hepatitis can be divided into two types of (1) to massive liver necrosis characterized by cell necrosis. Reduce the liver, liver cell lysis disappeared, only a small amount of remaining liver cells surrounding hepatic lobule. General non-regeneration and fibrous tissue, remnants of liver cells and small bile duct with cholestasis. (Two) prominent edematous lesions of liver cells showed a significant wide range of balloon-like change, squeeze each other to form a "plant cell"-like, there are foci of liver cell necrosis. 2. Sub-acute severe hepatitis can see the old and new of different sizes ranging from sub-chunk, chunk of liver necrosis, and hepatic cells, the coexistence of nodular hyperplasia, periportal connective tissue proliferation. 3. With chronic severe hepatitis in chronic active hepatitis or liver cirrhosis based on the secondary sub-massive or massive hepatic necrosis. Involving multiple hepatic lobule, there are pseudo-lobular formation of a high degree of deformation of the organizational structure of the liver.