Hepatitis B virus
Encyclopedia
Hepatitis B is an infectious illness caused by hepatitis B virus
(HBV) which infects the liver
of hominoidea, including humans, and causes an inflammation
called hepatitis
. Originally known as "serum hepatitis", the disease has caused epidemic
s in parts of Asia
and Africa
, and it is endemic
in China
. More than 2 billion people have been infected with the hepatitis B virus, and this includes 350 million chronic carriers
of the virus. Transmission of hepatitis B virus results from exposure to infectious blood or body fluids such as semen and vaginal fluids, while viral DNA has been detected in the saliva, tears, and urine of chronic carriers with high titer DNA in serum. Perinatal infection is a major route of infection in endemic (mainly developing) countries. Other risk factors for developing HBV infection include working in a health care setting, transfusions, and dialysis, acupuncture, tattooing, extended overseas travel and residence in an institution.
However, Hepatitis B viruses cannot be spread by holding hands, sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding.
The acute illness causes liver inflammation, vomiting, jaundice
, and (rarely) death. Chronic hepatitis B may eventually cause cirrhosis
and liver cancer—a fatal disease with very poor response to current chemotherapy. The infection is preventable by vaccination
.
Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus
—and it has a circular genome
composed of partially double-stranded DNA
. The viruses replicate
through an RNA
intermediate form by reverse transcription, and in this respect they are similar to retrovirus
es. Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies
are found in infected people. Blood tests for these proteins and antibodies are used to diagnose the infection.
– an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice
. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.
Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a 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
(liver cancer). 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 the development of Membranous glomerulonephritis
(MGN).
is not yet known, though there is evidence that the receptor in the closely related duck hepatitis B virus
is carboxypeptidase D. HBV virions (DANE particle) bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. PreS and IgA receptors are accused of this interaction. HBV-preS specific receptors are primarily expressed 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, 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, particularly 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 cytokine
s, which are then used to purge HBV from viable hepatocytes. Although liver damage 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.
, blood transfusion
s, re-use of contaminated needles
& syringes, and vertical transmission
from mother to child during childbirth. Without intervention, a mother who is positive for HBsAg confers 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 is also positive for HBeAg. HBV can be transmitted between family members within households, possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV. However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor. And Shi et al. showed that breastfeeding after proper immunoprophylaxis did not contribute to MTCT of HBV.
Hepatitis B virus (HBV) is a member of the Hepadnavirus family
. The virus particle, (virion) consists of an outer lipid
envelope and an icosahedral
nucleocapsid core composed of protein
. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase
activity. The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses, with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg
), and is produced in excess during the life cycle of the virus.
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 viral DNA polymerase
. The genome is 3020–3320 nucleotides long (for the full-length strand) and 1700–2800 nucleotides long (for 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 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. 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, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced. 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.
viruses which use reverse transcription as a part of its replication process. The virus gains entry into the cell by binding to an unknown receptor on the surface of the cell and enters it by endocytosis
. 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 viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. 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 which are released from the cell or returned to the nucleus and re-cycled to produce even more copies. The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.
s (adr, adw, ayr, ayw) based on antigenic epitope
s presented on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing 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.
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.
Genotype A is most commonly found in the Americas, Africa, India and Western Europe. Genotype B is most commonly found in Asia and the United States. Genotype B1 dominates in Japan, B2 in China and Vietnam while B3 confined to Indonesia. B4 is confined to Vietnam. All these strains specify the serotype ayw1. B5 is most common in the Philippines. Genotype C is most common in Asia and the United States. Subgenotype C1 is common in Japan, Korea and China. C2 is common in China, South-East Asia and Bangladesh and C3 in Oceania. All these strains specify the serotype adrq. C4 specifying ayw3 is found in Aborigine
s from Australia. Genotype D is most commonly found in Southern Europe, India and the United States and has been divided into 8 subtypes (D1-D8). In Turkey genotype D is also the most common type. A pattern of defined geographical distribution is less evident with D1-D4 where these subgenotypes are widely spread within Europe, Africa and Asia. This may be due to their divergence having occurred before than of genotypes B and C. D4 appears to be the oldest split and is still the dominating subgenotype of D in Oceania. Type E is most commonly found in West and Southern Africa. Type F is most commonly found in Central and South America and has been divided into two subgroups (F1 and F2). Genotype G has an insertion of 36 nucleotides in the core gene and is found in France and the United States. Type H is most commonly found in Central and South America and California in United States. Africa has five genotypes (A-E). Of these the predominant genotypes are A in Kenya, B and D in Egypt, D in Tunisia, A-D in South Africa and E in Nigeria. Genotype H is probably split off from genotype F within the New World.
The tests, called assay
s, for detection of hepatitis B virus infection involve serum
or blood test
s that detect either viral antigens (proteins produced by the virus) or antibodies
produced by 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 is made of 180 or 240 copies of 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 to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.
Shortly after the appearance of the HBsAg, another antigen named as the 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 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 the HBsAg and the appearance of anti-HBs is called the window period
. A person negative for HBsAg but positive for anti-HBs has either 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 the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly 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.
PCR tests have been developed to detect and measure 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 load
s, characteristically have ground glass hepatocyte
s on biopsy.
Several vaccines have been developed for the prevention of hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection. However, currently, it is made using a synthetic recombinant DNA
technology that does not contain blood products. One cannot be infected with hepatitis B from this vaccine.
The risk of vertical transmission to the newborn can be drastically reduced from 20%-90% to 5%-10% by administering to the newborn hepatitis B vaccine (HBV 1) and hepatitis B immune globulin (HBIG) within 12 hours of birth, followed by a second dose of hepatitis B vaccine (HBV 2) at 1-2 months and a third dose at and no earlier than 6 months (24 weeks). Since 2% of infants vaccinated will not develop immunity after the first three dose series, infants born to hepatitis B positive mothers are tested at 9 months for hepatitis B surface antigen (HBsAg) and the antibody to the hepatitis B surface antigen (anti-HBs); if post-vaccination test results indicate that the child is still susceptible, a second three dose series at (0, 1 and 6 months) is administered. If the child is still susceptible after the second series, a third series is not recommended.
Following vaccination, hepatitis B surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia. The vaccine is administered in either two-, three-, or four-dose schedules into infants and adults, which provides protection for 85–90% of individuals. Protection has been observed to last 12 years in individuals who show adequate initial response to the primary course of vaccinations, and that immunity is predicted to last at least 25 years.
Unlike hepatitis A
, hepatitis B does not generally spread through water and food. Instead, it is transmitted through body fluids; prevention is thus the avoidance of such transmission: unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission during child birth. Infants may be vaccinated at birth.
Shi, et al. showed that besides the WHO recommended joint immunoprophylaxis starting from the newborn, multiple injections of small doses of hepatitis B immune globulin
(HBIg, 200–400 IU per month), or oral lamivudine (100 mg per day) in HBV carrier mothers with a high degree of infectiousness (>106 copies/ml) in late pregnancy (the last three months of pregnancy), effectively and safely prevent HBV intrauterine transmission, which provide new insight into prevention of HBV at the earliest stage.
Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. Currently, there are seven medications licensed for treatment of hepatitis B infection in the United States. These include antiviral
drugs lamivudine
(Epivir), adefovir
(Hepsera), tenofovir (Viread), telbivudine
(Tyzeka) and entecavir
(Baraclude) and the two immune system
modulators interferon alpha-2a
and PEGylated interferon alpha-2a (Pegasys). 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 the genotype
of the infecting virus or the patient'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).
Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 90%.
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 is ~45% in types A and B but only 25–30% in types C and D.
In July 2005, researchers identified an association between a host-derived DNA-binding protein and the amount of HBV replication in the liver. Controlling the level of production of this protein could be used to treat hepatitis B.
Treatment lasts from 6 months to a year, depending on medication and genotype.
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 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 only occur 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
is more common in people with hepatitis B infection.
are at risk for HBV reactivation. The current view is that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell
function in the liver.
and northern Europe
. Routes of infection include vertical transmission (such as through childbirth), early life horizontal transmission (bites, lesions, and sanitary habits), and adult horizontal transmission (sexual contact, intravenous drug use). The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary methods, although other factors may also be important. In moderate prevalence areas, which include Eastern Europe, Russia
, and Japan
, where 2–7% of the population is chronically infected, the disease is predominantly spread among children. In high prevalence areas such as China
and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa
, transmission during childhood is a significant factor. The prevalence of chronic HBV infection in areas of high endemicity is at least 8%. As of 2010, China has 120 million infected people, followed by India and Indonesia with 40 million and 12 million respectively. According to WHO
, an estimated 600,000 people die every year related to the infection.
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 as suffering from serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Lurman's paper, now regarded as 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 virus was not discovered until 1965 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 Australian aboriginal people. Although a virus had been suspected since the research published by MacCallum in 1947, D.S. Dane and others discovered the virus particle in 1970 by electron microscopy. By the early 1980s the genome
of the virus had been sequenced, and the first vaccines were being tested.
Hepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
(HBV) which infects the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
of hominoidea, including humans, and causes an inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
called hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
. Originally known as "serum hepatitis", the disease has caused epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
s in parts of Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, and it is endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
in China
Hepatitis B in China
Hepatitis B is endemic in China. Of the 350 million individuals worldwide infected with the hepatitis B virus , one-third reside in China. As of 2006 China has immunized 11.1 million children in its poorest provinces as part of several programs initiated by the Chinese government and as part of the...
. More than 2 billion people have been infected with the hepatitis B virus, and this includes 350 million chronic carriers
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
of the virus. Transmission of hepatitis B virus results from exposure to infectious blood or body fluids such as semen and vaginal fluids, while viral DNA has been detected in the saliva, tears, and urine of chronic carriers with high titer DNA in serum. Perinatal infection is a major route of infection in endemic (mainly developing) countries. Other risk factors for developing HBV infection include working in a health care setting, transfusions, and dialysis, acupuncture, tattooing, extended overseas travel and residence in an institution.
However, Hepatitis B viruses cannot be spread by holding hands, sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding.
The acute illness causes liver inflammation, vomiting, jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, and (rarely) death. Chronic hepatitis B may eventually cause cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
and liver cancer—a fatal disease with very poor response to current chemotherapy. The infection is preventable by vaccination
Hepatitis B vaccine
Hepatitis B vaccine is a vaccine developed for the prevention of hepatitis B virus infection. The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen . It is produced by yeast cells, into which the genetic code for HBsAg has been inserted...
.
Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus
DNA virus
A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA but may also be single-stranded DNA . DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses...
—and it has a circular genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
composed of partially double-stranded DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. The viruses replicate
Self-replication
Self-replication is any behavior of a dynamical system that yields construction of an identical copy of that dynamical system. Biological cells, given suitable environments, reproduce by cell division. During cell division, DNA is replicated and can be transmitted to offspring during reproduction...
through an RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
intermediate form by reverse transcription, and in this respect they are similar to retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es. Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
are found in infected people. Blood tests for these proteins and antibodies are used to diagnose the infection.
Signs and symptoms
Acute infection with hepatitis B virus is associated with acute viral hepatitisHepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
– an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.
Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
(liver cancer). Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
and liver cancer. Hepatitis B virus has been linked to the development of Membranous glomerulonephritis
Membranous glomerulonephritis
Membranous glomerulonephritis is a slowly progressive disease of the kidney affecting mostly patients between ages of 30 and 50 years, usually Caucasian.It is one of the more common forms of nephrotic syndrome.-Terminology:...
(MGN).
Pathogenesis
Hepatitis B virus primarily interferes with the functions of the liver by replicating in liver cells, known as hepatocytes. The receptorReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
is not yet known, though there is evidence that the receptor in the closely related duck hepatitis B virus
Duck hepatitis B virus
Duck Hepatitis B virus, abbreviated DHBV, is part of the Avihepadnavirus genus of the Hepadnaviridae, and is the causal agent of duck hepatitis B....
is carboxypeptidase D. HBV virions (DANE particle) bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. PreS and IgA receptors are accused of this interaction. HBV-preS specific receptors are primarily expressed 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, 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, particularly 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 cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s, which are then used to purge HBV from viable hepatocytes. Although liver damage 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.
Transmission
Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. Possible forms of transmission include sexual contactSexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...
, blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s, re-use of contaminated needles
Needle sharing
Needle sharing is the practice of intravenous drug-users by which a syringe is shared by multiple individuals to administer intravenous drugs, and is a primary vector for diseases which can be transmitted through blood ....
& syringes, and vertical transmission
Vertical transmission
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission...
from mother to child during childbirth. Without intervention, a mother who is positive for HBsAg confers 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 is also positive for HBeAg. HBV can be transmitted between family members within households, possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV. However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor. And Shi et al. showed that breastfeeding after proper immunoprophylaxis did not contribute to MTCT of HBV.
Structure
Hepadnaviridae
Hepadnaviruses are a family of viruses which can cause liver infections in humans and animals. There are two recognized genera:*Genus Orthohepadnavirus; type species: Hepatitis B virus...
. The virus particle, (virion) consists of an outer lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
envelope and an icosahedral
Icosahedron
In geometry, an icosahedron is a regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. It is one of the five Platonic solids....
nucleocapsid core composed of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
activity. The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses, with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg
Hbsag
HBsAg is the surface antigen of the Hepatitis-B-Virus . It indicates current Hepatitis B infection.-Structure and function:The capsid of a virus has different surface proteins from the rest of the virus which act as antigens...
), and is produced in excess during the life cycle of the virus.
Genome
The genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of HBV is made of circular DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
. The genome is 3020–3320 nucleotides long (for the full-length strand) and 1700–2800 nucleotides long (for the short length-strand). The negative-sense, (non-coding), is complementary to the viral mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
. The viral DNA is found in the nucleus soon after infection of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
from the (-) sense strand and a short sequence of RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
from the (+) sense strand. Non-coding bases are removed from 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
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
processing of the pre-core protein. The DNA polymerase
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
is encoded by gene P. Gene S is the gene that codes for the surface antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
(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, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced. 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.
Replication
The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviralRetrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
viruses which use reverse transcription as a part of its replication process. The virus gains entry into the cell by binding to an unknown receptor on the surface of the cell and enters it by endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. 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 viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. 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
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
core protein and the viral DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
. These four viral transcripts undergo additional processing and go on to form progeny virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies. The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.
Serotypes and genotypes
The virus is divided into four major serotypeSerotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
s (adr, adw, ayr, ayw) based on antigenic epitope
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
s presented on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing 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.
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.
Genotype A is most commonly found in the Americas, Africa, India and Western Europe. Genotype B is most commonly found in Asia and the United States. Genotype B1 dominates in Japan, B2 in China and Vietnam while B3 confined to Indonesia. B4 is confined to Vietnam. All these strains specify the serotype ayw1. B5 is most common in the Philippines. Genotype C is most common in Asia and the United States. Subgenotype C1 is common in Japan, Korea and China. C2 is common in China, South-East Asia and Bangladesh and C3 in Oceania. All these strains specify the serotype adrq. C4 specifying ayw3 is found in Aborigine
Australian Aborigines
Australian Aborigines , also called Aboriginal Australians, from the latin ab originem , are people who are indigenous to most of the Australian continentthat is, to mainland Australia and the island of Tasmania...
s from Australia. Genotype D is most commonly found in Southern Europe, India and the United States and has been divided into 8 subtypes (D1-D8). In Turkey genotype D is also the most common type. A pattern of defined geographical distribution is less evident with D1-D4 where these subgenotypes are widely spread within Europe, Africa and Asia. This may be due to their divergence having occurred before than of genotypes B and C. D4 appears to be the oldest split and is still the dominating subgenotype of D in Oceania. Type E is most commonly found in West and Southern Africa. Type F is most commonly found in Central and South America and has been divided into two subgroups (F1 and F2). Genotype G has an insertion of 36 nucleotides in the core gene and is found in France and the United States. Type H is most commonly found in Central and South America and California in United States. Africa has five genotypes (A-E). Of these the predominant genotypes are A in Kenya, B and D in Egypt, D in Tunisia, A-D in South Africa and E in Nigeria. Genotype H is probably split off from genotype F within the New World.
Diagnosis
Assay
An assay is a procedure in molecular biology for testing or measuring the activity of a drug or biochemical in an organism or organic sample. A quantitative assay may also measure the amount of a substance in a sample. Bioassays and immunoassays are among the many varieties of specialized...
s, for detection of hepatitis B virus infection involve serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
or blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s that detect either viral antigens (proteins produced by the virus) or antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
produced by 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 is made of 180 or 240 copies of 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
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
antibodies to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.
Shortly after the appearance of the HBsAg, another antigen named as the 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 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 the HBsAg and the appearance of anti-HBs is called the window period
Window period
In medicine, the window period for a test designed to detect a specific disease is the time between first infection and when the test can reliably detect that infection...
. A person negative for HBsAg but positive for anti-HBs has either 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 the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly 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.
PCR tests have been developed to detect and measure the amount of HBV DNA, called the viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
, in clinical specimens. These tests are used to assess a person's infection status and to monitor treatment. Individuals with high viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
s, characteristically have ground glass hepatocyte
Ground glass hepatocyte
In liver pathology, a ground glass hepatocyte, abbreviated GGH, is a liver parenchymal cell with a flat hazy and uniformly dull appearing cytoplasm on light microscopy...
s on biopsy.
Prevention
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
technology that does not contain blood products. One cannot be infected with hepatitis B from this vaccine.
The risk of vertical transmission to the newborn can be drastically reduced from 20%-90% to 5%-10% by administering to the newborn hepatitis B vaccine (HBV 1) and hepatitis B immune globulin (HBIG) within 12 hours of birth, followed by a second dose of hepatitis B vaccine (HBV 2) at 1-2 months and a third dose at and no earlier than 6 months (24 weeks). Since 2% of infants vaccinated will not develop immunity after the first three dose series, infants born to hepatitis B positive mothers are tested at 9 months for hepatitis B surface antigen (HBsAg) and the antibody to the hepatitis B surface antigen (anti-HBs); if post-vaccination test results indicate that the child is still susceptible, a second three dose series at (0, 1 and 6 months) is administered. If the child is still susceptible after the second series, a third series is not recommended.
Following vaccination, hepatitis B surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia. The vaccine is administered in either two-, three-, or four-dose schedules into infants and adults, which provides protection for 85–90% of individuals. Protection has been observed to last 12 years in individuals who show adequate initial response to the primary course of vaccinations, and that immunity is predicted to last at least 25 years.
Unlike hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
, hepatitis B does not generally spread through water and food. Instead, it is transmitted through body fluids; prevention is thus the avoidance of such transmission: unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission during child birth. Infants may be vaccinated at birth.
Shi, et al. showed that besides the WHO recommended joint immunoprophylaxis starting from the newborn, multiple injections of small doses of hepatitis B immune globulin
Hepatitis B immune globulin
Hepatitis B immune globulin is a human immune globulin that is used to prevent the development of hepatitis B.-Preparation:HBIG is prepared from the plasma of donors who have high antibody levels of the hepatitis B surface antigen. It is extracted from the Cohn Fraction II...
(HBIg, 200–400 IU per month), or oral lamivudine (100 mg per day) in HBV carrier mothers with a high degree of infectiousness (>106 copies/ml) in late pregnancy (the last three months of pregnancy), effectively and safely prevent HBV intrauterine transmission, which provide new insight into prevention of HBV at the earliest stage.
Treatment
Acute hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously. Early antiviral treatment may only be required in fewer than 1% of patients, 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 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.Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. Currently, there are seven medications licensed for treatment of hepatitis B infection in the United States. These include antiviral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
drugs lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
(Epivir), adefovir
Adefovir
Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor .-Uses:...
(Hepsera), tenofovir (Viread), telbivudine
Telbivudine
Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo and Tyzeka...
(Tyzeka) and entecavir
Entecavir
Entecavir INN , abbreviated ETV, is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude ....
(Baraclude) and the two immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
modulators interferon alpha-2a
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
and PEGylated interferon alpha-2a (Pegasys). The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated
PEGylation
PEGylation is the process of covalent attachment of polyethylene glycol polymer chains to another molecule, normally a drug or therapeutic protein. PEGylation is routinely achieved by incubation of a reactive derivative of PEG with the target macromolecule...
interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
, which is injected only once weekly. However, some individuals are much more likely to respond than others and this might be because of the genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
of the infecting virus or the patient's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
(the amount of virus particles as measured in the blood).
Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 90%.
Response to treatment differs between the genotypes. Interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
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 is ~45% in types A and B but only 25–30% in types C and D.
In July 2005, researchers identified an association between a host-derived DNA-binding protein and the amount of HBV replication in the liver. Controlling the level of production of this protein could be used to treat hepatitis B.
Treatment lasts from 6 months to a year, depending on medication and genotype.
Prognosis
Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear 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 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
Hepatitis D
Hepatitis D, also referred to as hepatitis D virus and classified as Hepatitis delta virus, is a disease caused by a small circular enveloped RNA virus. It is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a subviral satellite because it can propagate only in the...
(HDV) can only occur with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. Polyarteritis nodosa
Polyarteritis nodosa
Polyarteritis nodosa is a vasculitis of medium & small-sized arteries, which become swollen and damaged from attack by rogue immune cells. Polyarteritis nodosa is also called Kussmaul disease or Kussmaul-Maier disease...
is more common in people with hepatitis B infection.
Reactivation
Hepatitis B virus DNA persists in the body after infection and in some people the disease recurs. Although rare, reactivation is seen most often in people with impaired immunity. HBV goes through cycles of replication and non-replication. Approximately 50% of patients experience acute reactivation. Male patients with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than patients with lower levels. Patients who undergo chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
are at risk for HBV reactivation. The current view is that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
function in the liver.
Epidemiology
In 2004, an estimated 350 million individuals were infected worldwide. National and regional prevalence ranges from over 10% in Asia to under 0.5% in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and northern Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
. Routes of infection include vertical transmission (such as through childbirth), early life horizontal transmission (bites, lesions, and sanitary habits), and adult horizontal transmission (sexual contact, intravenous drug use). The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary methods, although other factors may also be important. In moderate prevalence areas, which include Eastern Europe, Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
, and Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, where 2–7% of the population is chronically infected, the disease is predominantly spread among children. In high prevalence areas such as China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, transmission during childhood is a significant factor. The prevalence of chronic HBV infection in areas of high endemicity is at least 8%. As of 2010, China has 120 million infected people, followed by India and Indonesia with 40 million and 12 million respectively. According to WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
, an estimated 600,000 people die every year related to the infection.
History
The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885. An outbreak of smallpoxSmallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph
Lymph
Lymph is considered a part of the interstitial fluid, the fluid which lies in the interstices of all body tissues. Interstitial fluid becomes lymph when it enters a lymph capillary...
from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
and were diagnosed as suffering from serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Lurman's paper, now regarded as a classical example of an epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
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
Arsphenamine
Arsphenamine, also known as Salvarsan and 606, is a drug that was used beginning in the 1910s to treat syphilis and trypanosomiasis...
for the treatment of syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
. The virus was not discovered until 1965 when Baruch Blumberg, then working at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH), discovered the Australia antigen (later known to be hepatitis B surface antigen, or HBsAg) in the blood of Australian aboriginal people. Although a virus had been suspected since the research published by MacCallum in 1947, D.S. Dane and others discovered the virus particle in 1970 by electron microscopy. By the early 1980s the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of the virus had been sequenced, and the first vaccines were being tested.