133-459: HBeAg is a hepatitis B viral protein , produced by the HBcAg reading frame. It is an indicator of active viral replication ; this means the person infected with Hepatitis B can likely transmit the virus on to another person (i.e. the person is infectious). HBeAg is considered a marker for cccDNA replication. HBeAg is an antigen that can be found between the icosahedral nucleocapsid core and
266-472: A "sandwich" shape, the immunoglobulin fold , held together by a disulfide bond. Secreted antibodies can occur as a single Y-shaped unit, a monomer . However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units). IgG can also form hexamers, though no J chain
399-458: A 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma . Of those infected between the age of one to six, 70% will clear the infection. Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid . Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. Polyarteritis nodosa
532-523: A B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a " naive B lymphocyte ." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of
665-600: A Y shape. In humans and most other mammals , an antibody unit consists of four polypeptide chains ; two identical heavy chains and two identical light chains connected by disulfide bonds . Each chain is a series of domains : somewhat similar sequences of about 110 amino acids each. These domains are usually represented in simplified schematics as rectangles. Light chains consist of one variable domain V L and one constant domain C L , while heavy chains contain one variable domain V H and three to four constant domains C H 1, C H 2, ... Structurally an antibody
798-485: A classical example of an epidemiological study, proved that contaminated lymph was the source of the outbreak. Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used, and, more importantly, reused, for administering Salvarsan for the treatment of syphilis . The largest recorded outbreak of hepatitis B was the infection of up to 330,000 American soldiers during World War II. The outbreak has been blamed on
931-578: A day of birth. The hepatitis B vaccine was the first vaccine capable of preventing cancer, specifically liver cancer. Most vaccines are given in three doses over a course of days. A protective response to the vaccine is defined as an anti-HBs antibody concentration of at least 10 mIU/ml in the recipient's serum. The vaccine is more effective in children and 95 percent of those vaccinated have protective levels of antibody. This drops to around 90% at 40 years of age and to around 75 percent in those over 60 years. The protection afforded by vaccination
1064-527: A decrease in cytokine expression. HBeAg is dispensable for replication, as mutant viruses with defects in the pre-C region are both infectious and pathogenic. Hepatitis B Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) that affects the liver ; it is a type of viral hepatitis . It can cause both acute and chronic infection . Many people have no symptoms during an initial infection. For others, symptoms may appear 30 to 180 days after becoming infected and can include
1197-441: A distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes. The chromosomal region that encodes an antibody
1330-542: A given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This
1463-419: A higher risk. Immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver. The risk of reactivation varies depending on the serological profile; those with detectable HBsAg in their blood are at the greatest risk, but those with only antibodies to the core antigen are also at risk. The presence of antibodies to the surface antigen, which are considered to be
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#17327797932191596-408: A huge number of antibodies, each with different paratopes , and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells. RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without
1729-440: A manifestation of immunological memory. In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells , which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in
1862-489: A marker of immunity, does not preclude reactivation. Treatment with prophylactic antiviral drugs can prevent the serious morbidity associated with HBV disease reactivation. At least 296 million people, or 3.8% of the world's population, had chronic HBV infection as of 2019. Another 1.5 million cases of acute HBV infection also occurred that year. Regional prevalences across the globe range from around 7.5% in Africa to 0.5% in
1995-400: A mast cell, triggering its degranulation : the release of molecules stored in its granules. Binds to allergens and triggers histamine release from mast cells and basophils , and is involved in allergy . Humans and other animals evolved IgE to protect against parasitic worms , though in the present, IgE is primarily related to allergies and asthma. Although The antibody isotype of
2128-610: A more recent origin for all HBV genotypes. The evolution of HBV in humans was shown to reflect known events of human history such as the first peopling of the Americas during the late Pleistocene and the Neolithic transition in Europe. Ancient DNA studies have also showed that some ancient hepatitis viral strains still infect humans, while other strains became extinct. The earliest record of an epidemic caused by hepatitis B virus
2261-494: A normal immune system who were vaccinated. Only rare chronic infections have been documented. Vaccination is particularly recommended for high risk groups including: health workers, people with chronic kidney failure , and men who have sex with men. Both types of the hepatitis B vaccine, the plasma-derived vaccine (PDV) and the recombinant vaccine (RV) are of similar effectiveness in preventing infection in both healthcare workers and chronic kidney failure groups. One difference
2394-444: A part of a virus that is essential for its invasion). More narrowly, an antibody ( Ab ) can refer to the free (secreted) form of these proteins, as opposed to the membrane-bound form found in a B cell receptor. The term immunoglobulin can then refer to both forms. Since they are, broadly speaking, the same protein, the terms are often treated as synonymous. To allow the immune system to recognize millions of different antigens,
2527-425: A rapid onset of sickness with nausea , vomiting , yellowish skin , fatigue , dark urine, and abdominal pain . Symptoms during acute infection typically last for a few weeks, though some people may feel sick for up to six months. Deaths resulting from acute stage HBV infections are rare. An HBV infection lasting longer than six months is usually considered chronic. The likelihood of developing chronic hepatitis B
2660-640: A result. The infection may be entirely asymptomatic and may go unrecognized. Chronic infection with hepatitis B virus may be asymptomatic or may be associated with chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to
2793-462: A secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells. Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. herpes zoster ). Durable protection from infections caused by
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#17327797932192926-423: A significant number of cases in the 1980s; however, this has become less common with improved sterilization. The hepatitis B viruses cannot be spread by holding hands, sharing eating utensils, kissing, hugging, coughing, sneezing, or breastfeeding. The infection can be diagnosed 30 to 60 days after exposure. The diagnosis is usually confirmed by testing the blood for parts of the virus and for antibodies against
3059-432: A specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers , which are capable of signal transduction . A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate
3192-429: A strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis . Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities
3325-459: A template for transcription of four viral mRNAs by host RNA polymerase. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase . These four viral transcripts undergo additional processing and go on to form progeny virions that are released from the cell or returned to the nucleus and re-cycled to produce even more copies. The long mRNA
3458-493: A virus had been suspected since the research published by Frederick MacCallum in 1947, David Dane and others discovered the virus particle in 1970 by electron microscopy . In 1971, the FDA issued its first-ever blood supply screening order to blood banks. By the early 1980s the genome of the virus had been sequenced, and the first vaccines were being tested. Antibodies An antibody ( Ab ) or immunoglobulin ( Ig )
3591-546: A yellow fever vaccine made with contaminated human blood serum, and after receiving the vaccinations about 50,000 soldiers developed jaundice. The virus was not discovered until 1966 when Baruch Blumberg , then working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be hepatitis B surface antigen, or HBsAg) in the blood of Aboriginal Australian people. Although
3724-408: Is 50 to 100 times more infectious than human immunodeficiency virus (HIV) . HBV can be transmitted through several routes of infection. In vertical transmission , HBV is passed from mother to child (MTCT) during childbirth. Without intervention, a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother
3857-437: Is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses , including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens . Antigen literally means "antibody generator", as it
3990-459: Is a member of the hepadnavirus family . The virus particle ( virion ) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of core protein . These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus
4123-747: Is also moderate, with studies placing India's infection rate between 2-4%. Countries with low HBV prevalence include Australia (0.9%), those in the WHO European Region (which average 1.5%), and most countries in North and South America (which average 0.28%). In the United States, an estimated 0.26% of the population was living with HBV infection as of 2018. Findings of HBV DNA in ancient human remains have shown that HBV has infected humans for at least ten millennia, both in Eurasia and in
HBeAg - Misplaced Pages Continue
4256-522: Is also partitioned into two antigen-binding fragments (Fab), containing one V L , V H , C L , and C H 1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes ( dimers , trimers, etc.), and to bind effector molecules more easily. In an electrophoresis test of blood proteins , antibodies mostly migrate to
4389-532: Is also positive for HBeAg . Early life horizontal transmission can occur through bites, lesions, certain sanitary habits, or other contact with secretions or saliva containing HBV. Adult horizontal transmission is known to occur through sexual contact , blood transfusions and transfusion with other human blood products, re-use of contaminated needles and syringes. Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-transmission (MTCT) of HBV. Hepatitis B virus (HBV)
4522-414: Is associated with acute viral hepatitis , an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice . The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as
4655-415: Is called affinity maturation . Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells . Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by
4788-448: Is closer to human IgG2 than human IgG1 in terms of its function. The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity , which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of
4921-544: Is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point. Antibodies are heavy (~150 k Da ) proteins of about 10 nm in size, arranged in three globular regions that roughly form
5054-401: Is higher for those who are infected with HBV at a younger age. About 90% of those infected during or shortly after birth develop chronic hepatitis B, while less than 10% of those infected after the age of five develop chronic cases. Most of those with chronic disease have no symptoms; however, cirrhosis and liver cancer eventually develop in about 25% of those with chronic HBV. The virus
5187-483: Is initiated and mediated by the CTLs, antigen -nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver. The tests, called assays , for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by
5320-507: Is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes ( IGH@ ) is found on chromosome 14 , and the loci containing lambda and kappa light chain genes ( IGL@ and IGK@ ) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between
5453-423: Is long lasting even after antibody levels fall below 10 mIU/ml. For newborns of HBsAg-positive mothers: hepatitis B vaccine alone, hepatitis B immunoglobulin alone, or the combination of vaccine plus hepatitis B immunoglobulin, all prevent hepatitis B occurrence. Furthermore, the combination of vaccine plus hepatitis B immunoglobulin is superior to vaccine alone. This combination prevents HBV transmission around
HBeAg - Misplaced Pages Continue
5586-505: Is made of 180 or 240 copies of the core protein, alternatively known as hepatitis B core antigen, or HBcAg . During this 'window' in which the host remains infected but is successfully clearing the virus, IgM antibodies specific to the hepatitis B core antigen ( anti-HBc IgM ) may be the only serological evidence of disease. Therefore, most hepatitis B diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG). Shortly after
5719-449: Is more common in people with hepatitis B infection. A number of different tests are available to determine the degree of cirrhosis present. Transient elastography (FibroScan) is the test of choice, but it is expensive. Aspartate aminotransferase to platelet ratio index may be used when cost is an issue. Hepatitis B virus DNA remains in the body after infection, and in some people, including those that do not have detectable HBsAg,
5852-478: Is most prevalent in Africa (affecting 7.5% of the continent's population) and in the Western Pacific region (5.9%). Infection rates are 1.5% in Europe and 0.5% in the Americas. According to some estimates, about a third of the world's population has been infected with hepatitis B at one point in their lives. Hepatitis B was originally known as "serum hepatitis". Acute infection with hepatitis B virus
5985-502: Is no different from the risk in spontaneous conception. Those at high risk of infection should be tested as there is effective treatment for those who have the disease. Groups that screening is recommended for include those who have not been vaccinated and one of the following: people from areas of the world where hepatitis B occurs in more than 2%, those with HIV, intravenous drug users, men who have sex with men, and those who live with someone with hepatitis B. Screening during pregnancy
6118-462: Is one of the smallest enveloped animal viruses. The 42 nm virions, which are capable of infecting liver cells known as hepatocytes , are referred to as "Dane particles". In addition to the Dane particles, filamentous and spherical bodies lacking a core can be found in the serum of infected individuals. These particles are not infectious and are composed of the lipid and protein that forms part of
6251-458: Is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as TLR ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in
6384-400: Is present. The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large (the order from surface to
6517-405: Is recommended in the United States. Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised . On the other hand, treatment of chronic infection may be necessary to reduce
6650-430: Is required. IgA tetramers and pentamers have also been reported. Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex . Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc. Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with antibodies. An extreme example
6783-625: Is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities. The main categories of antibody action include the following: More indirectly, an antibody can signal immune cells to present antibody fragments to T cells , or downregulate other immune cells to avoid autoimmunity . Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in
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#17327797932196916-410: Is the clumping, or agglutination , of red blood cells with antibodies in blood typing to determine blood groups : the large clumps become insoluble, leading to visually apparent precipitation . The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when
7049-463: Is the most common form. Other immune-mediated hematological disorders, such as essential mixed cryoglobulinemia and aplastic anemia have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined; therefore, they probably should not be considered etiologically linked to HBV. Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. HBV
7182-463: Is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking
7315-450: Is then transported back to the cytoplasm where the virion P protein (the DNA polymerase) synthesizes DNA via its reverse transcriptase activity. The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins, and into eight major genotypes (A–H). The genotypes have a distinct geographical distribution and are used in tracing
7448-529: Is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue. Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding
7581-630: Is transmitted by exposure to infectious blood or body fluids . In areas where the disease is common , infection around the time of birth or from contact with other people's blood during childhood are the most frequent methods by which hepatitis B is acquired. In areas where the disease is rare, intravenous drug use and sexual intercourse are the most frequent routes of infection . Other risk factors include working in healthcare, blood transfusions , dialysis , living with an infected person, travel in countries with high infection rates, and living in an institution. Tattooing and acupuncture led to
7714-454: Is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment. Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions , found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand
7847-701: Is ~45% in types A and B but only 25–30% in types C and D. It seems unlikely that the disease will be eliminated by 2030, the goal set in 2016 by WHO. However, progress is being made in developing therapeutic treatments. In 2010, the Hepatitis B Foundation reported that 3 preclinical and 11 clinical-stage drugs were under development, based on largely similar mechanisms. In 2020, they reported that there were 17 preclinical- and 32 clinical-stage drugs under development, using diverse mechanisms. Hepatitis B virus infection may be either acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear
7980-416: The adaptive immune system , though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the complement system in
8113-535: The genotype of the infecting virus or the person's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment
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#17327797932198246-736: The iota (ι) chain, are found in other vertebrates like sharks ( Chondrichthyes ) and bony fishes ( Teleostei ). In most placental mammals , the structure of antibodies is generally the same. Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier. Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies. The antibody's paratope interacts with
8379-437: The "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization ; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill
8512-400: The 'e' antigen ( anti-HBe ) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication. If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen ( anti-HBs and anti HBc IgG ). The time between the removal of
8645-509: The Americas. The primary method of HBV transmission and the prevalence of chronic HBV infection in specific regions often correspond with one another. In populations where HBV infection rates are 8% or higher, which are classified as high prevalence, vertical transmission (usually occurring during birth) is most common, though rates of early childhood transmission can also be significant among these populations. In 2021, 19 African countries had infection rates ranging between 8-19%, placing them in
8778-571: The Americas. This disproved the belief that hepatitis B originated in the New World and spread to Europe around 16th century. Hepatitis B virus subgenotype C4 is exclusively present in Australian aborigines, suggesting an ancient origin as much as 50,000 years old. However, analyses of ancient HBV genomes suggested that the most recent common ancestor of all known human HBV strains was dated to between 20,000 and 12,000 years ago, pointing to
8911-614: The BCRs from most other cell signaling receptors. These patches may improve the efficiency of the cellular immune response . In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences. Antibodies can come in different varieties known as isotypes or classes . In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2. The prefix "Ig" stands for immunoglobulin , while
9044-513: The F V region. It is the subregion of Fab that binds to an antigen. More specifically, each variable domain contains three hypervariable regions – the amino acids seen there vary the most from antibody to antibody. When the protein folds, these regions give rise to three loops of β-strands , localized near one another on the surface of the antibody. These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen. Three CDRs from each of
9177-458: The Fc region and influence interactions with effector molecules. The N-terminus of each chain is situated at the tip. Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily : it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands , forming two beta sheets in a Greek key motif . The sheets create
9310-489: The Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway . Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across
9443-457: The HBsAg and the appearance of anti-HBs is called the window period . A person negative for HBsAg but positive for anti-HBs either has cleared an infection or has been vaccinated previously. Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase (ALT) levels and inflammation of
9576-491: The V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals . In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates
9709-500: The World Health Organization recommended tenofovir or entecavir as first-line agents. Those with current cirrhosis are in most need of treatment. The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon , which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of
9842-450: The adaptive immune system is regulated by interactions between idiotypes. The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen. Effector cells (such as macrophages or natural killer cells ) bind via their Fc receptors (FcR) to
9975-424: The amount of HBV DNA, called the viral load , in clinical specimens. These tests are used to assess a person's infection status and to monitor treatment. Individuals with high viral loads , characteristically have ground glass hepatocytes on biopsy. Vaccines for the prevention of hepatitis B have been routinely recommended for babies since 1991 in the United States. The first dose is generally recommended within
10108-410: The antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Between species, while classes and subclasses of antibodies may be shared (at least in name), their functions and distribution throughout the body may be different. For example, mouse IgG1
10241-686: The antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below. Somatic recombination of immunoglobulins, also known as V(D)J recombination , involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains , but only V and J segments are found in Ig light chains . Multiple copies of
10374-562: The antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants. Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces , hydrogen bonds , hydrophobic interactions , and van der Waals forces . This means binding between antibody and antigen
10507-421: The antigen-binding sites at both tips of the antibody come in an equally wide variety. The rest of the antibody structure is much less variable; in humans, antibodies occur in five classes , sometimes called isotypes : IgA , IgD , IgE , IgG , and IgM . Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, IgG4; IgA1 and IgA2). The class refers to the functions triggered by
10640-494: The appearance of the HBsAg, another antigen called hepatitis B e antigen ( HBeAg ) will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to
10773-491: The available medications can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2024, there are seven medications licensed for the treatment of hepatitis B infection in the United States. These include antiviral medications lamivudine , adefovir , tenofovir disoproxil , tenofovir alafenamide , telbivudine , and entecavir , and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a . In 2015,
10906-401: The bacterium directly (bacteriolysis). To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate . Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against
11039-434: The bloodstream, they are said to be part of the humoral immune system . Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating
11172-424: The body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in
11305-477: The bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in
11438-432: The cell by binding to NTCP on the surface and being endocytosed . Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The partially double-stranded, circular viral DNA is then made fully double stranded by HBV DNA polymerase, transforming the genome into covalently closed circular DNA (cccDNA). This cccDNA serves as
11571-430: The cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell . In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane -bound form. Some daughter cells of the activated B cells undergo isotype switching , a mechanism that causes the production of antibodies to change from IgM or IgD to
11704-423: The classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Antibodies are produced exclusively by B cells in response to antigens where initially, antibodies are formed as membrane-bound receptors, but upon activation by antigens and helper T cells, B cells differentiate to produce soluble antibodies. Many natural antibodies are directed against
11837-403: The constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from
11970-435: The development of membranous glomerulonephritis (MGN). Symptoms outside of the liver are present in 1–10% of HBV-infected people and include serum-sickness–like syndrome , acute necrotizing vasculitis ( polyarteritis nodosa ), membranous glomerulonephritis, and papular acrodermatitis of childhood ( Gianotti–Crosti syndrome ). The serum-sickness–like syndrome occurs in the setting of acute hepatitis B , often preceding
12103-466: The development of therapeutic treatments to cure chronic hepatitis B, as well as preventing its transmission and using vaccines to prevent new infections. An estimated 296 million people, or 3.8% of the global population, had chronic hepatitis B infections as of 2019. Another 1.5 million developed acute infections that year, and 820,000 deaths occurred as a result of HBV. Cirrhosis and liver cancer are responsible for most HBV-related deaths. The disease
12236-410: The disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. These antibodies undergo quality checks in the endoplasmic reticulum (ER), which contains proteins that assist in proper folding and assembly. Rejection of xenotransplantated organs
12369-478: The disease recurs. Although rare, reactivation is seen most often following alcohol or drug use, or in people with impaired immunity. HBV goes through cycles of replication and non-replication. Approximately 50% of overt carriers experience acute reactivation. Males with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than people with lower levels. Although reactivation can occur spontaneously, people who undergo chemotherapy have
12502-414: The diversity of the antibody pool and impacts the antibody's antigen-binding affinity . Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive
12635-583: The earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exception), are produced through genetic rearrangements (rather than being encoded directly in germline ), and are
12768-602: The early phases of the immune response (classically described as arising extrafollicularly rather than from the germinal center ) which have the potential to differentiate further into plasma cells. The literature is sloppy at times and often describes plasmablasts as just short-lived plasma cells- formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated ), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen
12901-489: The end of 2021. To further prevent infection, the WHO recommends testing all donated blood for hepatitis B before using it for transfusion. Using antiviral prophylaxis to prevent mother-to-child transmission is also recommended, as is following safe sex practices, including the use of condoms . In 2016, the WHO set a goal of eliminating viral hepatitis as a threat to global public health by 2030. Achieving this goal would require
13034-460: The ends of the (−) sense strand and the ends are rejoined. There are four known genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. In some rare strains of the virus known as hepatitis B virus precore mutants , no HBeAg
13167-838: The evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination. There are two other genotypes I and J but they are not universally accepted as of 2015. The diversity of genotypes is not shown equally in the world. For example, A, D, and E genotypes have been seen in Africa prevalently while B and C genotypes are observed in Asia as widespread. Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A–F). Two further types have since been described (G and H). Most genotypes are now divided into subgenotypes with distinct properties. Hepatitis B virus primarily interferes with
13300-592: The functions of the liver by replicating in hepatocytes . A functional receptor is NTCP . There is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D . The virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS-specific receptors are expressed primarily on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells. During HBV infection,
13433-414: The genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation , by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains. This serves to increase
13566-846: The heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen. Typically though, only a few residues contribute to most of the binding energy. The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls , or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes . The structures of CDRs have been clustered and classified by Chothia et al. and more recently by North et al. and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits
13699-449: The hepatitis B vaccine is between 98% and 100% effective in preventing infection. The vaccine is administered in several doses; after an initial dose, two or three more vaccine doses are required at a later time for full effect. The World Health Organization (WHO) recommends infants receive the vaccine within 24 hours after birth when possible. National programs have made the hepatitis B vaccine available for infants in 190 countries as of
13832-527: The high prevalence category. High prevalence of HBV also exists in Mongolia . In moderate prevalence areas where 2–7% of the population is chronically infected, the disease is predominantly spread horizontally, often among children, but also vertically. China's HBV infection rate is at the higher end of the moderate prevalence classification with an infection rate of 6.89% as of 2019. HBV prevalence in India
13965-506: The host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus-specific cytotoxic T lymphocytes (CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines , which are then used to purge HBV from viable hepatocytes. Although liver damage
14098-498: The host. Interpretation of these assays is complex. The hepatitis B surface antigen ( HBsAg ) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle
14231-433: The infection spontaneously within weeks to months. Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, this drops to 30% for younger children, and only 5% of newborns that acquire the infection from their mother at birth will clear the infection. This population has
14364-414: The inside: pre-S1, pre-S2, and S ), middle (pre-S2, S), and small (S) are produced. There is a myristyl group, which plays an important role in infection, on the amino-terminal end of the preS1 part of the large (L) protein. In addition to that, N terminus of the L protein have virus attachment and capsid binding sites. Because of that, the N termini of half of the L protein molecules are positioned outside
14497-769: The invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer . The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens. Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination , other foreign antigen exposure or passive immunization . These antibodies can activate
14630-462: The last, gamma globulin fraction. Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ . This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies. The variable domains can also be referred to as
14763-463: The lipid envelope (the outer most layer of the hepatitis b virus ). However, HBeAg is considered "nonparticulate" or "secretory". While both HBeAg and HBcAg are made from the same reading frame (multiple protein products can be produced from the same DNA sequence and when the genes "ORF Core" and "Pre C" are translated together, the result is HBeAg), HBeAg is secreted and accumulates in serum as an immunologically distinct soluble antigen . Hence
14896-483: The liver, if they are in the immune clearance phase of chronic infection. Carriers who have seroconverted to HBeAg negative status, in particular those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others. However, it is possible for individuals to enter an "immune escape" with HBeAg-negative hepatitis. PCR tests have been developed to detect and measure
15029-511: The membrane and the other half positioned inside the membrane. The function of the protein coded for by gene X is not fully understood but it is associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth regulating molecules. The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known pararetroviruses : non- retroviruses that still use reverse transcription in their replication process. The virus gains entry into
15162-498: The newborn infant. No randomized control trial has been conducted to assess the effects of hepatitis B vaccine during pregnancy for preventing infant infection. All those with a risk of exposure to body fluids such as blood should be vaccinated, if not already. Testing to verify effective immunization is recommended and further doses of vaccine are given to those who are not sufficiently immunized. In 10- to 22-year follow-up studies there were no cases of hepatitis B among those with
15295-439: The onset of jaundice. The clinical features are fever, skin rash , and polyarteritis . The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute hepatitis B . About 30–50% of people with acute necrotizing vasculitis (polyarteritis nodosa) are HBV carriers. HBV-associated nephropathy has been described in adults but is more common in children. Membranous glomerulonephritis
15428-557: The other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system. In mammals there are two types of immunoglobulin light chain , which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as
15561-587: The pathogen in cells that recognize their Fc region. Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose , mast cells and neutrophils will degranulate , natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of
15694-455: The pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway . Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens). Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of
15827-603: The placenta, from the mother to the fetus. In addition to this, binding to FcRn endows IgG with an exceptionally long half-life relative to other plasma proteins of 3-4 weeks. IgG3 in most cases (depending on allotype) has mutations at the FcRn binding site which lower affinity for FcRn, which are thought to have evolved to limit the highly inflammatory effects of this subclass. Antibodies are glycoproteins , that is, they have carbohydrates (glycans) added to conserved amino acid residues. These conserved glycosylation sites occur in
15960-437: The presence of these proteins, V(D)J recombination would not occur. After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion ) thus each B cell can produce antibodies containing only one kind of variable chain. Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells,
16093-463: The reason why the presence of both proteins together acts as a marker of viral replication, and why antibodies to these antigens are a marker of declining replication. The presence of HBeAg in the serum of patients can serve as a marker of active replication in chronic hepatitis. Although the function of HBeAg was not clearly understood, one study demonstrated that it downregulated Toll-like receptor 2 expression on hepatocytes and monocytes leading to
16226-425: The risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase , a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype. Treatment duration when medication is taken by mouth, however, is more variable and usually longer than one year. Although none of
16359-437: The same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching
16492-433: The short length-strand). The negative-sense (non-coding) is complementary to the viral mRNA . The viral DNA is found in the nucleus soon after infection of the cell . The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (−) sense strand and a short sequence of RNA from the (+) sense strand. Non-coding bases are removed from
16625-444: The suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively. The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region. The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in
16758-487: The surface of the virion, which is called the surface antigens ( HBsAg ), and is produced in excess during the life cycle of the virus. The genome of HBV is made of circular DNA , but it is unusual because the DNA is not fully double-stranded . One end of the full length strand is linked to the HBV DNA polymerase . The genome is 3020–3320 nucleotides long (for the full-length strand) and 1700–2800 nucleotides long (for
16891-440: The table. For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells , often a sole contributor to asthma (though other pathways exist as do exist symptoms very similar to yet not technically asthma). The antibody's variable region binds to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on
17024-455: The time of birth in 86% to 99% of cases. Tenofovir given in the second or third trimester can reduce the risk of mother to child transmission by 77% when combined with hepatitis B immunoglobulin and the hepatitis B vaccine, especially for pregnant women with high hepatitis B virus DNA levels. However, there is not sufficient evidence that the administration of hepatitis B immunoglobulin alone during pregnancy, might reduce transmission rates to
17157-430: The understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities. In the framework of the immune network theory , CDRs are also called idiotypes. According to immune network theory,
17290-412: The variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of
17423-492: The virus. It is one of five main hepatitis viruses: A , B, C , D , and E . During an initial infection, care is based on a person's symptoms. In those who develop chronic disease, antiviral medication such as tenofovir or interferon may be useful; however, these drugs are expensive. Liver transplantation is sometimes recommended for cases of cirrhosis or hepatocellular carcinoma . Hepatitis B infection has been preventable by vaccination since 1982. As of 2022,
17556-485: Was made by Lurman in 1885. An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed with serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Lurman's paper, now regarded as
17689-483: Was noticed among the health worker group: the RV intramuscular route was significantly more effective compared with the RV intradermal route of administration. In assisted reproductive technology , sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of transmission from mother to child with IVF
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