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Hepatitis B is an
infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
caused by the ''
hepatitis B virus Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Classification Hepatitis B ...
'' (HBV) that affects the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
; it is a type of viral hepatitis. It can cause both acute and
chronic infection Chronic may refer to: * Chronic condition, a condition or disease that is persistent or otherwise long-lasting in its effects * Chronic toxicity, a substance with toxic effects after continuous or repeated exposure * Chronic (film), ''Chronic'' ...
. Many people have no symptoms during an initial infection. For others, symptoms may appear 30 to 180 days after becoming infected and can include a rapid onset of sickness with
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
,
vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
, yellowish skin,
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
, yellow urine, and
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...
. 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 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
and
liver cancer Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondar ...
eventually develop in about 25% of those with chronic HBV. The virus is transmitted by exposure to infectious
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
or
body fluids Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the Body (biology), body of an organism. In lean healthy adult men, the total body water is about 60% (60–67%) of the total Human body weight, body weight; it ...
. In areas where the disease is
common Common may refer to: As an Irish surname, it is anglicised from Irish Gaelic surname Ó Comáin. Places * Common, a townland in County Tyrone, Northern Ireland * Boston Common, a central public park in Boston, Massachusetts * Cambridge Com ...
, 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 Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous, location). Intravenous ...
and
sexual intercourse Sexual intercourse (also coitus or copulation) is a sexual activity typically involving the insertion of the Erection, erect male Human penis, penis inside the female vagina and followed by Pelvic thrust, thrusting motions for sexual pleasure ...
are the most frequent
routes of infection In medicine, public health, and biology, transmission is the passing of a pathogen causing communicable disease from an infected host individual or group to a particular individual or group, regardless of whether the other individual was previou ...
. Other risk factors include working in healthcare,
blood transfusions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but ...
,
dialysis Dialysis may refer to: * Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric po ...
, living with an infected person, travel in countries with high infection rates, and living in an institution.
Tattoo A tattoo is a form of body modification made by inserting tattoo ink, dyes, or pigments, either indelible or temporary, into the dermis layer of the skin to form a design. Tattoo artists create these designs using several tattooing processes ...
ing and
acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientif ...
led to a significant number of cases in the 1980s; however, this has become less common with improved sterilization. The 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 An antibody (Ab) or immunoglobulin (Ig) 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 caus ...
against the virus. It is one of five main
hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...
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 Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobial ...
such as
tenofovir Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for pr ...
or
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
may be useful; however, these drugs are expensive.
Liver transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...
is sometimes recommended for cases of cirrhosis or
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...
. Hepatitis B infection has been preventable by
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
since 1982. As of 2022, 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 The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(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 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 A condom is a sheath-shaped barrier device used during sexual intercourse to reduce the probability of pregnancy or a sexually transmitted infection (STI). There are both external condoms, also called male condoms, and internal (female) ...
. In 2016, the WHO set a goal of eliminating viral hepatitis as a threat to global
public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the de ...
by 2030. Achieving this goal would require 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 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".


Signs and symptoms

Acute infection with virus is associated with acute viral
hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...
, 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 Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
. 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 Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...
and may die as a result. The infection may be entirely asymptomatic and may go unrecognized. Chronic infection with virus may be asymptomatic or may be associated with chronic inflammation of the liver (chronic hepatitis), leading to
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
over a period of several years. This type of infection dramatically increases the incidence of
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...
(HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
as it increases their risk for
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
and liver cancer. virus has been linked to the development of
membranous glomerulonephritis Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.). It is the sec ...
(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 Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs' ...
), membranous glomerulonephritis, and papular acrodermatitis of childhood ( Gianotti–Crosti syndrome). The serum-sickness–like syndrome occurs in the setting of acute , often preceding the onset of jaundice. The clinical features are fever,
skin rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked ...
, and polyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute . About 30–50% of people with acute necrotizing vasculitis (polyarteritis nodosa) are HBV carriers. HBV-associated
nephropathy Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipap ...
has been described in adults but is more common in children. Membranous glomerulonephritis is the most common form. Other immune-mediated
hematological Hematology ( spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the production ...
disorders, such as essential mixed
cryoglobulinemia Cryoglobulinemia is a rare medical condition characterized by the presence of cryoglobulins in the blood. Cryoglobulins are abnormal proteins composed of immunoglobulins and sometimes complement components. Cryoglobulins specifically form g ...
and
aplastic anemia Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Normally, blood cells are produced in the bone marrow by stem cells that reside there, but patients with 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.


Cause


Transmission

Transmission of virus results from exposure to infectious blood or body fluids containing blood. HBV is 50 to 100 times more infectious than human immunodeficiency virus (HIV). HBV can be transmitted through several routes of infection. In
vertical transmission Vertical transmission of symbionts is the transfer of a microbial symbiont from the parent directly to the offspring.  Many metazoan species carry symbiotic bacteria which play a mutualistic, commensal, or parasitic role.  A symbiont is acq ...
, HBV is passed from mother to child (MTCT) during childbirth. Without intervention, a mother who is positive for
HBsAg HBsAg (also known as the Australia antigen) is the surface antigen of the hepatitis B virus (HBV). Its presence in blood indicates existing hepatitis B infection. Structure and function The viral envelope of an enveloped virus has different su ...
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 is also positive for
HBeAg 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 infe ...
. Early life horizontal transmission can occur through bites, lesions, certain sanitary habits, or other contact with secretions. Though HBV is found in virtually every bodily secretion and excretion, only blood, semen, and vaginal secretions have been shown to be infective. Adult horizontal transmission is known to occur through sexual contact,
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
s 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.


Virology


Structure

virus (HBV) is a member of the hepadnavirus family. The virus particle (
virion A virion (plural, ''viria'' or ''virions'') is an inert virus particle capable of invading a Cell (biology), cell. Upon entering the cell, the virion disassembles and the genetic material from the virus takes control of the cell infrastructure, t ...
) consists of an outer
lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
envelope and an
icosahedral In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes . The plural can be either "icosahedra" () or "icosahedrons". There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrical tha ...
nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...
core composed of core
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
. These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has
reverse transcriptase A reverse transcriptase (RT) is an enzyme used to convert RNA genome to DNA, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobi ...
activity. The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses. The 42 nm virions, which are capable of infecting liver cells known as
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...
s, 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 the surface of the virion, which is called the surface antigens (
HBsAg HBsAg (also known as the Australia antigen) is the surface antigen of the hepatitis B virus (HBV). Its presence in blood indicates existing hepatitis B infection. Structure and function The viral envelope of an enveloped virus has different su ...
), and is produced in excess during the life cycle of the virus.


Genome

The
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of HBV is made of circular
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
, but it is unusual because the DNA is not fully
double-stranded A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
. One end of the full length strand is linked to the HBV DNA polymerase. The genome is 3020–3320
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
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 In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
. The viral DNA is found in the
nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...
soon after infection of the
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
from the (−) sense strand and a short sequence of
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
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 Genetic code is a set of rules used by living cells to translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished by the ribosome, which links prote ...
is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by
proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
processing of the pre-core protein. In some rare strains of the virus known as hepatitis B virus precore mutants, no HBeAg is present. The DNA
polymerase In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by ...
is encoded by gene P. Gene S is the gene that codes for the surface
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
(HBsAg). The HBsAg gene is one long
open reading frame In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...
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,
polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...
s of three different sizes called large (the order from surface to 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 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.


Pathogenesis

The life cycle of virus is complex. is one of a few known pararetroviruses: non-
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
es that still use
reverse transcription A reverse transcriptase (RT) is an enzyme used to convert RNA genome to DNA, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B virus, hepatitis B to replicate their genomes, by retrot ...
in their replication process. The virus gains entry into the cell by binding to
NTCP Sodium/bile acid cotransporter also known as the Na+- taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the ''SLC10A1'' (solute carrier family 10 member 1) gene. Stru ...
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 a template for transcription of four viral
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
s 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 A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...
core protein and the viral
DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...
. 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 is then transported back to the cytoplasm where the virion P protein (the DNA polymerase) synthesizes DNA via its reverse transcriptase activity. In addition to its nuclear cccDNA reservoir, fragments of hepatitis B virus DNA can integrate into the host genome, particularly in cases of chronic infection, and this integration is implicated in the development of liver cancer.


Serotypes and genotypes

The virus is divided into four major
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or Cell (biology), cells are classified together based on their shared reactivity ...
s (adr, adw, ayr, ayw) based on antigenic
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 binds to the epitope is called a paratope. Although e ...
s presented on its envelope proteins, and into eight major genotypes (A–H). 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. 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.


Mechanisms

virus primarily interferes with the functions of the liver by replicating in
hepatocytes A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bile ...
. A functional
receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
is
NTCP Sodium/bile acid cotransporter also known as the Na+- taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the ''SLC10A1'' (solute carrier family 10 member 1) gene. Stru ...
. There is evidence that the receptor in the closely related
duck hepatitis B virus Duck hepatitis B virus, abbreviated DHBV, is part of the genus '' Avihepadnavirus'' of the ''Hepadnaviridae'', and is the causal agent of duck hepatitis B. DHBV is a small DNA virus with a diameter of 40–45 nm. The viral envelope is ma ...
is
carboxypeptidase D Carboxypeptidase D can refer to one of several enzymes. A family of serine carboxypeptidases (i.e. enzymes that use an active site serine residue) includes (, ''cereal serine carboxypeptidase II'', ''Saccharomyces cerevisiae KEX1 gene product'', '' ...
. 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, the host
immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
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 A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral
cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s, which are then used to purge HBV from viable hepatocytes. Although liver damage is initiated and mediated by the CTLs,
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
-nonspecific
inflammatory cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are general ...
s can worsen CTL-induced immunopathology, and
platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...
activated at the site of infection may facilitate the accumulation of CTLs in the liver.


Diagnosis

The tests, called
assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...
s, for detection of virus infection involve
serum Serum may refer to: Biology and pharmacology *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity *Serous fluid, any clear bodily fluid Places *Serum, Ind ...
or
blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...
s that detect either viral antigens (proteins produced by the virus) or
antibodies An antibody (Ab) or immunoglobulin (Ig) 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 caus ...
produced by the host. Interpretation of these assays is complex. The surface antigen (
HBsAg HBsAg (also known as the Australia antigen) is the surface antigen of the hepatitis B virus (HBV). Its presence in blood indicates existing hepatitis B infection. Structure and function The viral envelope of an enveloped virus has different su ...
) 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 the core protein, alternatively known as core antigen, or
HBcAg HBcAg (core antigen) is a hepatitis B viral protein. 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). Structure ...
. During this 'window' in which the host remains infected but is successfully clearing the virus,
IgM Immunoglobulin M (IgM) is the largest of several isotypes of antibodies (also known as immunoglobulin) that are produced by vertebrates. IgM is the first antibody to appear in the response to initial exposure to an antigen; causing it to also ...
antibodies specific to the core antigen (''anti-HBc IgM'') may be the only
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
evidence of disease. Therefore, most diagnostic panels contain HBsAg and total anti-HBc (both IgM and
IgG Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...
). Shortly after the appearance of the HBsAg, another antigen called e antigen (
HBeAg 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 infe ...
) may 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 virus do not produce the 'e' antigen, so this rule does not always hold true. Overall, only a minority of diagnosed cases of hepatitis B have been found to feature the 'e' antigen. 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 Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...
antibodies to the 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 In medicine, the window period for a test designed to detect a specific disease (particularly infectious disease) is the time between first infection and when the test can reliably detect that infection. In antibody-based testing, 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 carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum
alanine aminotransferase Alanine aminotransferase (ALT or ALAT), formerly alanine transaminase (ALT), and even earlier referred to as serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme () that was first ch ...
(ALT) levels and inflammation of 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 rare but possible for individuals to enter an "immune escape" with reactivated HBeAg-negative hepatitis, once again showing signs of disease despite previous complete immune system control. This results in high viral replication and faster progression towards cirrhosis, compared to the typical course of disease. These individuals will typically have detectable anti-HBe antibodies, but no detectable HBeAg in the serum. PCR tests have been developed to detect and measure the amount of HBV DNA, called the
viral load Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
, 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, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
s, characteristically have
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. The cytoplasm's granular homogeneous eosinophilic staining is caused by the pre ...
s on biopsy.


Prevention


Vaccine

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 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 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 the time of birth in 86% to 99% of cases.
Tenofovir Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for pr ...
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 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 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 Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
, 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 was noticed among the health worker group: the RV intramuscular route was significantly more effective compared with the RV intradermal route of administration.


Other

In
assisted reproductive technology Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation of ga ...
,
sperm washing Sperm washing is the process in which individual sperms are separated from the semen. Washed sperm is used in artificial insemination using the intrauterine insemination (IUI) technique and in in vitro fertilization (IVF). It may also be used to dec ...
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 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 Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
is recommended in the United States.


Treatment

Acute 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 Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
. On the other hand, treatment of chronic infection may be necessary to reduce the risk of
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
and liver cancer. Chronically infected individuals with persistently elevated serum
alanine aminotransferase Alanine aminotransferase (ALT or ALAT), formerly alanine transaminase (ALT), and even earlier referred to as serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme () that was first ch ...
, 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 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 infection in the United States. These include
antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
medications
lamivudine Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typi ...
,
adefovir Adefovir is a prescription medicine used to treat (chronic) infections with hepatitis B virus. A prodrug form of adefovir was previously called bis-POM PMEA, with trade names Preveon and Hepsera. It is an orally administered nucleotide analog re ...
,
tenofovir disoproxil Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for pr ...
,
tenofovir alafenamide Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease an ...
, telbivudine, and
entecavir Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is ...
, and the two
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
modulators interferon alpha-2a and PEGylated interferon alpha-2a. In 2015, 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 PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
, 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 The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
of the infecting virus or the person's heredity. The treatment reduces viral replication in the liver, thereby reducing the
viral load Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
(the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes.
Interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
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. 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.


Prognosis

virus infection may be either 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
or
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...
. Of those infected between the age of one to six, 70% will clear the infection.
Hepatitis D Hepatitis D is a type of viral hepatitis caused by the hepatitis delta virus (HDV). HDV is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a satellite (a type of subviral agent) because it can propagate only in ...
(HDV) can occur only with a concomitant infection, because HDV uses the HBV surface antigen to form a
capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...
. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.
Polyarteritis nodosa Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs' ...
is more common in people with infection.


Cirrhosis

A number of different tests are available to determine the degree of cirrhosis present.
Transient elastography Transience or transient may refer to: Music * ''Transient'' (album), a 2004 album by Gaelle * ''Transience'' (Steven Wilson album), 2015 * Transience (Wreckless Eric album) Science and engineering * Transient state, when a process variable or ...
(FibroScan) is the test of choice, but it is expensive. Aspartate aminotransferase to platelet ratio index may be used when cost is an issue.


Reactivation

virus DNA remains in the body after infection, and in some people, including those that do not have detectable HBsAg, 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 Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
have a higher risk.
Immunosuppressive drugs Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...
favor increased HBV replication while inhibiting
cytotoxic T cell A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular ...
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 a marker of immunity, does not preclude reactivation. Treatment with prophylactic antiviral drugs can prevent the serious morbidity associated with HBV disease reactivation.


Epidemiology

Approximately 254 million people had chronic HBV infection as of 2022. Another 1.2 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 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 the high prevalence category. High prevalence of HBV also exists in
Mongolia Mongolia is a landlocked country in East Asia, bordered by Russia to the north and China to the south and southeast. It covers an area of , with a population of 3.5 million, making it the world's List of countries and dependencies by po ...
. 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 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.


History

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 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 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 virus was made by Lurman in 1885. An outbreak of
smallpox Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (W ...
occurred in
Bremen Bremen (Low German also: ''Breem'' or ''Bräm''), officially the City Municipality of Bremen (, ), is the capital of the States of Germany, German state of the Bremen (state), Free Hanseatic City of Bremen (), a two-city-state consisting of the c ...
in 1883 and 1,289 shipyard employees were
vaccinated A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
with
lymph Lymph () is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the ori ...
from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
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 a classical example of an
epidemiological Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...
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 A hypodermic needle (from Greek ὑπο- (''hypo-'' = under), and δέρμα (''derma'' = skin)) is a very thin, hollow tube with one sharp tip. As one of the most important intravenous inventions in the field of drug administration, it is ...
that were used, and, more importantly, reused, for administering
Salvarsan Arsphenamine, also known as Salvarsan or compound 606, is an antibiotic drug that was introduced at the beginning of the 1910s as the first effective treatment for the deadly infectious diseases syphilis, relapsing fever, and African trypanosomias ...
for the treatment of
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
. 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 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 Baruch Samuel Blumberg (July 28, 1925 April 5, 2011), known as Barry Blumberg, was an American physician, geneticist, and co-recipient of the 1976 Nobel Prize in Physiology or Medicine (with Daniel Carleton Gajdusek), for his work on the hepa ...
, then working at the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
(NIH), discovered the Australia antigen (later known to be surface antigen, or HBsAg) in the blood of Aboriginal Australian people. Although 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 An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...
. In 1971, the FDA issued its first-ever blood supply screening order to blood banks. By the early 1980s the
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of the virus had been sequenced, and the first vaccines were being tested.


Society and culture

World Hepatitis Day World Hepatitis Day, observed on July 28 every year, aims to raise global awareness of hepatitis — a group of infectious diseases known as hepatitis A, B, C, D, and E — and encourage prevention, diagnosis and treatment. Hepatitis affec ...
, observed 28 July, aims to raise global awareness of and
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...
and encourage prevention, diagnosis, and treatment. It has been led by the World Hepatitis Alliance since 2007 and in May 2010, it received global endorsement from the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
.


See also

*
Infectious causes of cancer Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the wo ...
*
Oncovirus An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term ''oncornaviruses'' was used to denote their RNA virus origin. With the let ...


References


External links

* * {{Authority control Sexually transmitted diseases and infections Virus-related cutaneous conditions Infectious causes of cancer Wikipedia medicine articles ready to translate Wikipedia infectious disease articles ready to translate Vaccine-preventable diseases +B Viral hepatitis