Hepatitis B

Hepatitis B is an infectious inflammatory illness of the livercaused by the hepatitis B virus(HBV) that affects hominoidea,
including humans. Originally known as "serum hepatitis",[1]the disease has causedepidemics in parts of Asia andAfrica, and it
is endemic inChina.[2] About a third of the world population has been infected at one point in their lives, [3] including 350 million
who are chronic carriers.[4][dead link]
The virus is transmitted by exposure to infectious blood orbody fluids such as semen and vaginal fluids, while viral DNA has
been detected in the saliva, tears, and urine of chronic carriers.Perinatal infection is a major route of infection in endemic (mainly
developing) countries.[5] Other risk factors for developing HBV infection include working in a healthcare
setting,transfusions, dialysis, acupuncture, tattooing, sharing razors or toothbrushes with an infected person, travel in countries
where it is endemic, and residence in an institution.[3][6][7][8] However, hepatitis B viruses cannot be spread by holding hands,
sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding.[8][9]
The acute illness causes liver inflammation, vomiting, jaundice, and, rarely, death. Chronic hepatitis B may eventually
cause cirrhosis and liver cancera disease with poor response to all but a few current therapies.[10] The infection is preventable
by vaccination.[11]
Hepatitis B virus is a hepadnavirushepa from hepatotropic (attracted to the liver) and dna because it is a DNA virus[12]and it
has a circular genome of partially double-stranded DNA. The viruses replicate through an RNAintermediate form by reverse
transcription, which in practice relates them toretroviruses.[13] Although replication takes place in the liver, the virus spreads to
the blood where viral proteins and antibodies against them are found in infected people.[14] The hepatitis B virus is 50 to 100
times more infectious than HIV.[15][not in citation given]

Signs and symptoms[edit]

Acute infection with hepatitis B virus is associated with acute viral hepatitis an illness that begins with general ill-health, loss of
appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development ofjaundice. 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 people 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.[16]
Chronic infection with hepatitis B virus either may be 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). Across Europe hepatitis B and C cause approximately 50% hepatocellular
carcinomas.[17][18] 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).[19]
Symptoms outside of the liver are present in 110% of HBV-infected people and include serum-sicknesslike syndrome, acute
necrotizing vasculitis(polyarteritis nodosa), membranous glomerulonephritis, and papular acrodermatitis of childhood (Gianotti
Crosti syndrome).[20][21] The serum-sicknesslike syndrome occurs in the setting of acute hepatitis B, often preceding the onset
of jaundice.[22] The clinical features are fever, skin rash, and polyarteritis. The symptoms often subside shortly after the onset of
jaundice, but can persist throughout the duration of acute hepatitis B.[23]About 3050% of people with acute necrotizing vasculitis
(polyarteritis nodosa) are HBV carriers.[24] HBV-associated nephropathy has been described in adults but is more common in

children.[25][26] Membranous glomerulonephritis is the most common form.[23] Other immune-mediated hematologicaldisorders,
such as essential mixed cryoglobulinemia and aplastic anemia.[23]

Virology[edit]
Hepatitis B virus (HBV) is a member of the hepadnavirus family.[12] The virus particle (virion) consists of an outer lipid envelope
and an icosahedral nucleocapsidcore composed of protein. These virions are 30-42 nm in diameter. The nucleocapsid encloses
the viral DNA and a DNA polymerase that has reverse transcriptaseactivity.[13] 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,
and the 42 nM virions, which are capable of infecting hepatocytes, are referred to as "Dane particles".[27] 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
antigen (HBsAg), and is produced in excess during the life cycle of the virus.[28]

Genome[edit]

The genome organisation of HBV. The genes overlap.

The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fullydouble-stranded. One end of the full
length strand is linked to the viralDNA polymerase. The genome is 30203320 nucleotides long (for the full-length strand) and
17002800 nucleotides long (for the short length-strand).[29] The negative-sense (non-coding) is complementary to the
viral mRNA. The viral DNA is found in thenucleus soon after infection of thecell. The partially double-stranded DNA is rendered
fully double-stranded by completion of the (+) sense strand and removal of a proteinmolecule 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 byproteolytic 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.[30] 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. [31]

Replication[edit]

Hepatitis B virus replication

The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known pararetroviruses: non-retroviruses that still
use reverse transcription in their replication process. The virus gains entry into the cell by binding to NTCP [32] 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 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
viralmRNAs. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to
make the capsid core protein and the viral DNA polymerase. These four viral transcripts undergo additional processing and go
on to form progeny virions that are released from the cell or returned to the nucleus and re-cycled to produce even more
copies.[30][33] 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.

Serotypes and genotypes[edit]

The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes 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.[34][35]
Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A-F).[36] Two
further types have since been described (G and H).[37] Most genotypes are now divided into subgenotypes with distinct
properties.[38]
Distribution of genotypes
Genotype A is most commonly found in the Americas, Africa, India and Western Europe. It is divided into subgenotypes. Of
these subgenotype A1 is further subdivided into an Asian and an African clade.
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 adr. C4 specifying
ayw3 is found in Aborigines from Australia.[39]
Genotype D is most commonly found in Southern Europe, India and the United States and has been divided into 8 subtypes
(D1D8). In Turkey genotype D is also the most common type. A pattern of defined geographical distribution is less evident with
D1D4 where these subgenotypes are widely spread within Europe, Africa and Asia. This may be due to their divergence having
occurred before that 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.[40]
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.[39] Genotype H is probably split off from genotype F within the New World.[41]
Evolution
A Bayesian analysis of the genotypes suggests that the rate of evolution of the core protein gene is 1.127 (95% credible
interval 0.925-1.329) substitutions per site per year.[42]
The most recent common ancestor of genotypes A, B, D evolved in 1895 (95% confidence interval 1819-1959), 1829
(95% confidence interval 1690-1935) and 1880 (95% confidence interval 1783-1948) respectively.[42]

Mechanisms[edit]
Pathogenesis[edit]
Hepatitis B virus primarily interferes with the functions of the liver by replicating in liver cells, known as hepatocytes. A
functional receptor is NTCP.[32] There is evidence that the receptor in the closely related duck hepatitis B
virus iscarboxypeptidase D.[43][44] 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.[45]
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, in particular virusspecific cytotoxic T lymphocytes(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate
HBV infection by killing infected cells and producing antiviral cytokines, which are then used to purge HBV from viable
hepatocytes.[46] 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.[47]

Transmission[edit]

Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. Possible forms of
transmission include sexual contact,[48] blood transfusions and transfusion with other human blood products,[49] re-use of
contaminated needles and syringes,[50] and vertical transmission from mother to child (MTCT) 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. [51] However, at
least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor.[52] And Shi et al. showed that
breastfeeding after proper immunoprophylaxis did not contribute to MTCT of HBV.[53]

Diagnosis[edit]

Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.

Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person.

The tests, called assays, for detection of hepatitis B virus infection involveserum or blood tests that detect either viral antigens
(proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex.[54]
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. Therefore
most hepatitis B diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG).[55]
Shortly after the appearance of the HBsAg, another antigen called hepatitis Be 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.[56] 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.

Ground glass hepatocytes as seen in a chronic hepatitis B liver biopsy. H&E stain.

If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to
thehepatitis B surface antigen and core antigen (anti-HBs and anti HBc IgG).[12] 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 either has
cleared an infection or has been vaccinated previously.
Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers.[57] 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, 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.[58]
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.[59] Individuals with high viral loads,
characteristically have ground glass hepatocytes on biopsy.

Prevention[edit]
Main article: Hepatitis B vaccine
Vaccines for the prevention of hepatitis B have been routinely used since the early 1980s. The first vaccines contained
inactivated HBsAg that was derived from human plasma of hepatitis B virus carriers. Modern vaccines contain HBsAg from
yeast or mammalian cell cultures using recombinant DNA technology and have no risk of transmitting hepatitis B virus. Most
vaccines are given in three doses over a course of months. A protective response to the vaccine is defined as an anti-HBs
antibody concentration of at least10 mIU/ml in the recipient's serum. The vaccine is more effective in children and 95 per cent of
those vaccinated have protective levels of antibody. This drops to around 90% at forty years of age and to around 75 percent in
those over sixty. The protection afforded by vaccination is long lasting even after antibody levels fall below 10 mIU/ml.
Vaccination at birth is recommended for all infants of HBV infected mothers. A combination of hepatitis B immunoglobulin and an
accelerated course of HBV vaccine prevents perinatal HBV transmission in around 90% of cases.[60]
In assisted reproductive technology, The Practice Committee of the American Society for Reproductive Medicine advises
that sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been
effectively vaccinated.[61] In females with hepatitis B, the risk of vertical transmission during IVF is no different from the risk in
spontaneous conception.[61]

Treatment[edit]

The hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously. [62] Early
antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant
hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the
risk ofcirrhosis 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.[63] Treatment lasts from six months to a year,
depending on medication and genotype.[64]
Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver
damage. As of 2008, 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 twoimmune 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.[65] 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 person's heredity. The treatment reduces viral replication in the liver, thereby reducing
the viral load (the amount of virus particles as measured in the blood).[66] 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 2530% in types C and D.[67]

Prognosis[edit]
Hepatitis B 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. [68][dead link] This population has
a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma.[65]Of those infected between the age of one to six, 70%
will clear the infection.[69]
Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form
a capsid.[70] Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.[71]Polyarteritis nodosa is more
common in people with hepatitis B infection.

Reactivation[edit]
Hepatitis B virus DNA persists in the body after infection, and in some people the disease recurs.[72] Although rare, reactivation is
seen most often following alcohol or drug use,[73] or in people with impaired immunity.[74] 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,[75] people who undergochemotherapy have a higher risk.[76] Immunosuppressive drugs favor increased HBV
replication while inhibiting cytotoxic T cell function in the liver.[77][dead link]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.[76] Treatment with prophylactic antiviral drugs can prevent the serious morbidity associated with
HBV disease reactivation.[76]

Hepatitis B
Fact sheet N204
Updated July 2013

Key facts

Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.
The virus is transmitted through contact with the blood or other body fluids of an infected person.
About 600 000 people die every year due to the consequences of hepatitis B.
Hepatitis B is an important occupational hazard for health workers.
Hepatitis B is preventable with the currently available safe and effective vaccine.

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus. It is a major global health problem. It can
cause chronic liver disease and chronic infection and puts people at high risk of death from cirrhosis of the liver and liver cancer.
More than 240 million people have chronic (long-term) liver infections. About 600 000 people die every year due to the acute or
chronic consequences of hepatitis B.
A vaccine against hepatitis B has been available since 1982. Hepatitis B vaccine is 95% effective in preventing infection and its
chronic consequences, and was the first vaccine against a major human cancer.
Geographical distribution
Hepatitis B virus can cause an acute illness with symptoms that last several weeks, including yellowing of the skin and eyes
(jaundice), dark urine, extreme fatigue, nausea, vomiting and abdominal pain. Hepatitis B prevalence is highest in sub-Saharan Africa
and East Asia. Most people in these regions become infected with the hepatitis B virus during childhood and between 510% of the
adult population is chronically infected.
High rates of chronic infections are also found in the Amazon and the southern parts of eastern and central Europe. In the Middle East
and the Indian subcontinent, an estimated 25% of the general population is chronically infected. Less than 1% of the population in
western Europe and North America is chronically infected.
Transmission
In highly endemic areas, HBV is most commonly spread from mother to child at birth, or from person to person in early childhood.
Perinatal or early childhood transmission may also account for more than one third of chronic infections in areas of low endemicity,
although in those settings, sexual transmission and the use of contaminated needles, especially among injecting drug users, are the
major routes of infection.
The hepatitis B virus can survive outside the body for at least seven days. During this time, the virus can still cause infection if it
enters the body of a person who is not protected by the vaccine.
The hepatitis B virus is not spread by contaminated food or water, and cannot be spread casually in the workplace.
The incubation period of the hepatitis B virus is 75 days on average, but can vary from 30 to 180 days. The virus may be detected 30
to 60 days after infection and persists for variable periods of time.
Symptoms
Most people do not experience any symptoms during the acute infection phase. However, some people have acute illness with
symptoms that last several weeks, including yellowing of the skin and eyes (jaundice), dark urine, extreme fatigue, nausea, vomiting
and abdominal pain.
In some people, the hepatitis B virus can also cause a chronic liver infection that can later develop into cirrhosis of the liver or liver
cancer.
More than 90% of healthy adults who are infected with the hepatitis B virus will recover and be completely rid of the virus within six
months.

Who is at risk for chronic disease?

The likelihood that infection with the hepatitis B virus becomes chronic depends upon the age at which a person becomes infected.
Children less than 6 years of age who become infected with the hepatitis B virus are the most likely to develop chronic infections:
8090% of infants infected during the first year of life develop chronic infections;
3050%% of children infected before the age of 6 years develop chronic infections.
In adults:
<5% of otherwise healthy adults who are infected will develop chronic infection;
1525% of adults who become chronically infected during childhood die from hepatitis B-related liver cancer or cirrhosis.
Diagnosis
It is not possible, on clinical grounds, to differentiate hepatitis B from hepatitis caused by other viral agents and, hence, laboratory
confirmation of the diagnosis is essential. A number of blood tests are available to diagnose and monitor people with hepatitis B. They
can be used to distinguish acute and chronic infections.
Laboratory diagnosis of hepatitis B infection centres on the detection of the hepatitis B surface antigen HBsAg. WHO recommends
that all blood donations are tested for this marker to avoid transmission to recipients.
Acute HBV infection is characterized by the presence of HBsAg and immunoglobulin M (IgM) antibody to the core antigen, HBcAg.
During the initial phase of infection, patients are also seropositive for HBeAg.
Chronic infection is characterized by the persistence (>6 months) of HBsAg (with or without concurrent HBeAg). Persistence of
HBsAg is the principal marker of risk for developing chronic liver disease and hepatocellullar carcinoma (HCC) later in life.
The presence of HBeAg indicates that the blood and body fluids of the infected individual are highly contagious
Treatment
There is no specific treatment for acute hepatitis B. Care is aimed at maintaining comfort and adequate nutritional balance, including
replacement of fluids that are lost from vomiting and diarrhoea.
Some people with chronic hepatitis B can be treated with drugs, including interferon and antiviral agents. Treatment can slow the
progression of cirrhosis, reduce incidence of HCC and improve long term survival. Treatment, however, is not readily accessible in
many resource-constrained settings.
Liver cancer is almost always fatal and often develops in people at an age when they are most productive and have family
responsibilities. In developing countries, most people with liver cancer die within months of diagnosis. In high-income countries,
surgery and chemotherapy can prolong life for up to a few years.
People with cirrhosis are sometimes given liver transplants, with varying success.

Prevention

1.
2.

The hepatitis B vaccine is the mainstay of hepatitis B prevention. WHO recommends that all infants receive the hepatitis B vaccine as
soon as possible after birth, preferably within 24 hours.
The birth dose should be followed by 2 or 3 doses to complete the primary series. In most cases, 1 of the following 2 options is
considered appropriate:
a 3-dose schedule of hepatitis B vaccine, with the first dose (monovalent) being given at birth and the second and third (monovalent or
combined vaccine) given at the same time as the first and third doses of DTP vaccine; or
4 doses, where a monovalent birth dose is followed by 3 monovalent or combined vaccine doses, usually given with other routine
infant vaccines.
The complete vaccine series induces protective antibody levels in more than 95% of infants, children and young adults. Protection
lasts at least 20 years and is possibly lifelong.
All children and adolescents younger than 18 years old and not previously vaccinated should receive the vaccine if they live in
countries where there is low or intermediate endemicity. In those settings it is possible that more people in high risk groups may
acquire the infection and they should also be vaccinated. They include:
people who frequently require blood or blood products, dialysis patients, recipients of solid organ transplantations;
people interned in prisons;
injecting drug users;
household and sexual contacts of people with chronic HBV infection;
people with multiple sexual partners, as well as health-care workers and others who may be exposed to blood and blood products
through their work; and
travellers who have not completed their hepatitis B vaccination series should be offered the vaccine before leaving for endemic areas.
The vaccine has an excellent record of safety and effectiveness. Since 1982, over one billion doses of hepatitis B vaccine have been
used worldwide. In many countries, where 815% of children used to become chronically infected with the hepatitis B virus,
vaccination has reduced the rate of chronic infection to less than 1% among immunized children.

As of July 2011, 179 Member States vaccinate infants against hepatitis B as part of their vaccination schedules. This is a major
increase compared with 31 countries in 1992, the year that the World Health Assembly passed a resolution to recommend global
vaccination against hepatitis B. Furthermore, as of July 2011, 93 Member States have introduced the hepatitis B birth dose.
In addition, implementation of blood safety strategies, including quality-assured screening of all donated blood and blood components
used for transfusion can prevent transmission of HBV. Safe injection - unnecessary as well as unsafe injections - practices can protect
against HBV transmission. Furthermore, safer sex practices, including minimizing the number of partners and using barrier protective
measures (condoms), protect against transmission.

What is hepatitis B?
Hepatitis* B is a virus, or infection, that causes liver disease and inflammationof the liver. Viruses can cause sickness. For
example, the flu is caused by a virus. People can pass viruses to each other.
Inflammation is swelling that occurs when tissues of the body become injured or infected. Inflammation can cause organs
to not work properly.
*See the Pronunciation Guide for tips on how to say the underlined words.
[Top]

What is the liver?

The liver is an organ that does many important things. You cannot live without a liver.

Hepatitis B is a virus, or infection, that causes liver disease and inflammation of the liver.

The liver
removes harmful chemicals from your blood
fights infection
helps digest food
stores nutrients and vitamins
stores energy
[Top]

Who gets hepatitis B?

Anyone can get hepatitis B, but those more likely to are people who
were born to a mother with hepatitis B
are in contact with blood, needles, or body fluids at work
live with someone who currently has an active hepatitis B infection
have had more than one sex partner in the last 6 months or have a history of sexually transmitted disease
are on kidney dialysisthe process of filtering wastes and extra water from the body by means other than the
kidneys

 are taking medicines that suppress the immune system, such as steroids or chemotherapy medicines
have lived in or travel often to parts of the world where hepatitis B is common
are from Asian and Pacific Island nations
are infected with HIV or hepatitis C
have injected illegal drugs
work or live in a prison
had a blood transfusion or organ transplant before the mid-1980s
Also, men who have sex with men are more likely to get hepatitis B.
[Top]

How could I get hepatitis B?

You could get hepatitis B through contact with an infected persons blood, semen, or other body fluid. This contact could
occur by
being born to a mother with hepatitis B
getting an accidental stick with a needle that was used on an infected person
having unprotected sex with an infected person
having contact with blood or open sores of an infected person
sharing drug needles or other drug materials with an infected person
being tattooed or pierced with unsterilized tools that were used on an infected person
using an infected persons razor, toothbrush, or nail clippers

You could get hepatitis B from having unprotected sex with an infected person.

You cannot get hepatitis B from

shaking hands or holding hands with an infected person
being coughed or sneezed on by an infected person
hugging an infected person
sitting next to an infected person
sharing spoons, forks, and other eating utensils
drinking water or eating food
A baby cannot get hepatitis B from breast milk.
[Top]

What are the symptoms of hepatitis B?

Most people do not have any symptoms of hepatitis B. Adults and children ages 5 and older may have one or more of the
following symptoms:
feeling tired
muscle soreness
upset stomach
stomach pain
fever

 loss of appetite
diarrhea
dark-yellow urine
light-colored stools
yellowish eyes and skin, called jaundice
When symptoms occur, they can begin 2 to 5 months after coming into contact with the virus. See a doctor right away if
you or a child in your care has symptoms of hepatitis B.
[Top]

What is acute hepatitis B?

Acute hepatitis B is a short-term infection with the hepatitis B virus. Symptoms usually last several weeks but they can last
up to 6 months. The infection sometimes clears up because your body is able to fight off the infection and get rid of the
virus. Most healthy adults and children older than 5 who have hepatitis B get better without treatment.
[Top]

What is chronic hepatitis B?

Chronic hepatitis B is a long-lasting infection with the hepatitis B virus. Chronic hepatitis B occurs when the body cant get
rid of the hepatitis B virus. Children, especially infants, are more likely to get chronic hepatitis B, which usually has no
symptoms until signs of liver damage appear.
Without treatment, chronic hepatitis B can cause liver cancer or severe liver damage that leads to liver failure. Liver failure
occurs when the liver stops working properly.
[Top]

How is hepatitis B diagnosed?

A blood test will show if you have hepatitis B. Blood tests are done at a doctors office or outpatient facility. A blood
sample is taken using a needle inserted into a vein in your arm or hand. The blood sample is sent to a lab to test for
hepatitis B.
If you are at higher risk of getting hepatitis B, get tested. If you are pregnant, you should also get tested. Many people with
hepatitis B do not know they are infected. Early diagnosis and treatment can help prevent liver damage.

A blood test will show if you have hepatitis B.

Your doctor may suggest getting a liver biopsy if chronic hepatitis B is suspected. A liver biopsy is a test to take a small
piece of your liver to look for liver damage. The doctor may ask you to stop taking certain medicines before the test. You
may be asked to fast for 8 hours before the test.
During the test, you lie on a table with your right hand resting above your head. Medicine is applied to numb the area
where the biopsy needle will be inserted. If needed, sedatives and pain medicine are also given. The doctor uses a needle
to take a small piece of liver tissue. After the test, you must lie on your right side for up to 2 hours. You will stay 2 to 4
hours after the test before being sent home.
A liver biopsy is performed at a hospital or outpatient center by a doctor. The liver tissue is sent to a special lab where a
doctor looks at the tissue with a microscope and sends a report to your doctor.
[Top]

How is hepatitis B treated?

Hepatitis B is not usually treated unless it becomes chronic. Chronic hepatitis B is treated with medicines that slow or stop
the virus from damaging the liver.
Medicines for Chronic Hepatitis B
Your doctor will choose medicines or a combination of medicines that are likely to work for you. The doctor will closely
watch your symptoms and schedule regular blood tests to make sure treatment is working.
Medicines given by shots include
interferon
peginterferon
Medicines taken by mouth include
adefovir
entecavir
lamivudine
telbivudine
tenofovir
The length of treatment varies. Talk with your doctor before taking other prescription medicines and over-the-counter
medicines.
Liver Transplant
A liver transplant may be necessary if chronic hepatitis B causes severe liver damage that leads to liver failure. Symptoms
of severe liver damage include the symptoms of hepatitis B and
generalized itching
a longer than usual amount of time for bleeding to stop
easy bruising
swollen stomach or ankles
spiderlike blood vessels, called spider angiomas, that develop on the skin
Liver transplant is surgery to remove a diseased or injured liver and replace it with a healthy one from another person,
called a donor. If your doctors tell you that you need a transplant, you should talk with them about the long-term demands
of living with a liver transplant.
A team of surgeonsdoctors who specialize in surgeryperforms a liver transplant in a hospital. You will learn how to
take care of yourself after you go home and about the medicines youll need to take to protect your new liver. Medicines
taken after liver transplant surgery can prevent hepatitis B from coming back.
Testing for Liver Cancer
Having hepatitis B increases your risk for getting liver cancer, so your doctor may suggest an ultrasound test of the liver
every 6 to 12 months. Finding cancer early makes it more treatable. Ultrasound is a machine that uses sound waves to
create a picture of your liver. Ultrasound is performed at a hospital or radiology center by a specially trained technician.
The image, called a sonogram, can show the livers size and the presence of cancerous tumors.
[Top]

How can I avoid getting hepatitis B?

You can avoid getting hepatitis B by receiving the hepatitis B vaccine.
Vaccines are medicines that keep you from getting sick. Vaccines teach the body to attack specific viruses and infections.
The hepatitis B vaccine teaches your body to attack the hepatitis B virus.
Since the 1980s, a hepatitis B vaccine has been available and should be given to newborns and children in the United
States. Adults at higher risk of getting hepatitis B should also get the vaccine.
The hepatitis B vaccine is given in three shots over 6 months. You must get all three hepatitis B vaccine shots to be fully
protected.

You can avoid getting hepatitis B by receiving the hepatitis B vaccine.

If you are traveling to countries where hepatitis B is common, try to get all the shots before you go. If you dont have time
to get all the shots before you travel, get as many as you can. Even one shot may provide some protection against the
virus.
You can protect yourself and others from getting hepatitis B if you
use a condom during sex
do not share drug needles and other drug materials
do not donate blood or blood products
wear gloves if you have to touch another persons blood or open sores
do not share or borrow a toothbrush, razor, or nail clippers
make sure any tattoos or body piercings you get are done with sterile tools
tell your doctor and your dentist if you have hepatitis B
If you are pregnant and have hepatitis B, tell the doctor and staff who deliver your baby. The hepatitis B vaccine and
hepatitis B immune globulin should be given to your baby right after birth. The vaccine will greatly reduce the chance of
your baby getting the infection.

Wear gloves if you have to touch another persons blood or open sores.

[Top]

What should I do if I think I have been in contact with the hepatitis B virus?
See your doctor right away if you think you have been in contact with the hepatitis B virus. A dose of the hepatitis B
vaccine taken with a medicine called hepatitis B immune globulin may protect you from getting sick if taken shortly after
coming into contact with the hepatitis B virus.
[Top]

Eating, Diet, and Nutrition

If you have chronic hepatitis B, you should do things to take care of yourself, including eating a healthy diet. Avoid
drinking alcohol, which can harm the liver. Talk with your doctor before taking vitamins and other supplements.
[Top]

Points to Remember

Hepatitis B is a virus, or infection, that causes liver disease and inflammation of the liver.
Anyone can get hepatitis B, but some people are more likely to than others.
You could get hepatitis B through contact with an infected persons blood, semen, or other body fluid.
Most people do not have any symptoms of hepatitis B. Adults and children ages 5 and older may have symptoms.
See a doctor right away if you or a child in your care has symptoms of hepatitis B.
Acute hepatitis B is a short-term infection with the hepatitis B virus.
Chronic hepatitis B is a long-lasting infection with the hepatitis B virus. Chronic hepatitis B occurs when the body
cant get rid of the hepatitis B virus.
Children, especially infants, are more likely to get chronic hepatitis B.
A blood test will show if you have hepatitis B.
If you are at higher risk of getting hepatitis B, get tested. If you are pregnant, you should also get tested.
Many people with hepatitis B do not know they are infected. Early diagnosis and treatment can help prevent liver
damage.
Hepatitis B is usually not treated unless it becomes chronic. Chronic hepatitis B is treated with medicines that slow or
stop the virus from damaging the liver.
You can avoid getting hepatitis B by receiving the hepatitis B vaccine.
Tell your doctor and your dentist if you have hepatitis B.
If you are pregnant and have hepatitis B, tell the doctor and staff who deliver your baby.
See your doctor right away if you think you have been in contact with the hepatitis B virus.

Hepatitis B
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Hepatitis B is irritation and swelling (inflammation) of the liver due to infection with the hepatitis B virus (HBV).
Other types of viral hepatitis include:

Hepatitis A
Hepatitis C
Hepatitis D

Causes
Hepatitis B infection is caused by the hepatitis B virus (HBV).You can catch hepatitis B through contact with the blood or
body fluids (such as semen, vaginal fluids, and saliva) of a person who has the virus.
Exposure may occur:

After a needle stick or sharps injury

If any blood or other body fluid touches your skin, eyes or mouth

People who may be at risk of hepatitis B are those who:

Have unprotected sex with an infected partner

Receive blood transfusions (not common in the United States)
Have contact with blood at work (such as health care workers)
Have been on long-term kidney dialysis

Get a tattoo or acupuncture with unclean needles

Share needles during drug use
Share personal items (such as toothbrush, razor, and nail clippers) with a person who has the virus
Were born to a hepatitis-B infected mother

Symptoms
After you first become infected with the hepatitis B virus:

You may have no symptoms

You may feel sick for a period of days or weeks
You may become very ill very quickly (called fulminant hepatitis)

Symptoms of hepatitis B may not appear for up to 6 months after the time of infection. Early symptoms include:

Appetite loss
Fatigue
Low fever
Muscle and joint aches
Nausea and vomiting
Yellow skin and dark urine

Symptoms will go away in a few weeks to months if your body is able to fight off the infection. Some people never get rid
of the hepatitis B virus. This is called chronic hepatitis B.
People with chronic hepatitis may not have symptoms and not know they are infected. Over time, they may develop
symptoms of liver damage and cirrhosis of the liver.
You can spread the hepatitis B virus to other people even if you have no symptoms.
Exams and Tests
A series of blood tests called the hepatitis viral panel is done to help diagnose the condition.
The following tests are done to look for liver damage if you have chronic hepatitis B:

Albumin level
Liver function tests
Prothrombin time

You will also have a test to measure the level of HPV in your blood (viral load). This lets your doctors know how your
treatment is working.

Treatment
Acute hepatitis needs no treatment other than careful monitoring of liver and other body functions with blood tests. You
should get plenty of bed rest, drink plenty of fluids, and eat healthy foods.
Some patients with chronic hepatitis may be treated with antiviral medications or a medication called peginterferon. These
medications can decrease or remove hepatitis B from the blood and reduce the risk of cirrhosis and liver cancer. It is not
always clear which patients with chronic hepatitis B should receive drug therapy and when drug therapy should be started.
You are more likely to receive these medicines if:

Your liver function is becoming worse quickly

You develop symptoms of long-term liver damage
You have high levels of the hepatitis B virus in your blood

If you develop rapid liver failure, you may need a liver transplant. A liver transplant is the only cure in some cases of liver
failure.
Other recommendations:

Avoid alcohol.
Check with your doctor or nurse before taking any over-the-counter medications or herbal supplements. This
includes medications such as acetaminophen, aspirin, or ibuprofen.

Severe liver damage, or cirrhosis, can be caused by hepatitis B.

Support Groups
Some people benefit from attending a liver disease support group.
Outlook (Prognosis)
The acute illness usually goes away after 2 - 3 weeks. The liver usually returns to normal within 4 - 6 months in most
people.
Almost all newborns and about half of children who get hepatitis B develop the chronic condition. Very few adults who get
the virus develop chronic hepatitis B.
About 1 in 100 people who get hepatitis B dies from the condition.
There is a much higher rate of liver cancer in people who have chronic hepatitis B.

When to Contact a Medical Professional

Call your health care provider if:

You develop symptoms of hepatitis B

Hepatitis B symptoms do not go away in 2 - 3 weeks, or new symptoms develop
You belong to a high-risk group for hepatitis B and have not had the HBV vaccine.

Prevention
Children and people at high risk for hepatitis B should get the hepatitis B vaccine.

Babies should get a first dose of the hepatitis B vaccine at birth. They should have all three shots in the series by
age 6 months.
Children younger than age 19 who have not had the vaccine should get "catch-up" doses.
Health care workers and those who live with someone who has hepatitis B should get the vaccine.
Infants born to mothers who have acute hepatitis B or have had the infection in the past should get a special
hepatitis B vaccine within 12 hours of birth.

All blood used for blood transfusions is screened, so the chance of getting the virus in this way is very small.

The hepatitis B vaccine or a hepatitis immune globulin (HBIG) shot may help prevent infection if you receive it within 24
hours of contact with the virus.
Measures to avoid contact with blood and body fluids can help prevent the spread of hepatitis B from person to person.

Treatment to prevent hepatitis B infection after exposure

If you know you've been exposed to the hepatitis B virus, call your doctor immediately. Receiving an injection of hepatitis
B immune globulin within 24 hours of coming in contact with the virus may help protect you from developing hepatitis B.
Treatment for acute hepatitis B infection
If your doctor determines your hepatitis B infection is acute meaning it is short-lived and will go away on its own you
may not need treatment. Instead, your doctor will work to reduce any signs and symptoms you experience while your
body fights the infection. Your doctor may recommend follow-up blood tests to make sure the virus has left your body.
Treatment for chronic hepatitis B infection
If you've been diagnosed with chronic hepatitis B infection, your doctor may recommend:

Antiviral medications. Antiviral medications help fight the virus and slow its ability to damage your liver. Several
medications are available. Your doctor can suggest which medications may be most appropriate for you.

Liver transplant. If your liver has been severely damaged, a liver transplant may be an option. During a liver transplant,
the surgeon removes your damaged liver and replaces it with a healthy liver. Most transplanted livers come from
deceased donors, though a small number come from living donors.

Treatment of hepatitis B viral (HBV) infection depends on how active the virus is and whether you are at risk
for liver damage such as cirrhosis. Short-term (acute)hepatitis B usually goes away on its own. Home treatment is used to
relieve symptoms and help prevent spread of the virus. In long-term (chronic) HBV infection, treatment includes
monitoring the condition and using antiviral medicines to prevent liver damage. If hepatitis B has severely damaged your
liver, a liver transplant may be considered.
The American Association for the Study of Liver Disease has maderecommendations on who should receive antiviral
treatment for chronic hepatitis B based on the presence of hepatitis B antigens, level of HBV DNA, and the levels of
liver enzymes in your blood.4
Treatment of short-term (acute) hepatitis B infection
Initial treatment for hepatitis B infection depends on whether you:

Have been recently infected with the hepatitis B virus (HBV).

Have the symptoms of an acute HBV infection.
Have chronic HBV infection.
If you believe you have recently been exposed to HBV, you should receive a shot ofhepatitis B immunoglobulin
(HBIG) and the first of three immunization shots ofhepatitis B vaccine. It is important to receive this treatment within 7
days after a needle stick and within 2 weeks after sexual contact that may have exposed you to the virus. The sooner you
receive treatment after exposure, the more effective treatment is.

If you have the symptoms of acute hepatitis B, treatment with medicine is usually not needed. Home treatment usually will
relieve your symptoms and help prevent the spread of the virus. To help relieve symptoms and prevent the spread of the
infection:

Slow down. Reduce your activity level to match your energy level. Don't go to work or school unless your workload can be
lightened. Avoid strenuous exercise. As you start to feel better, go back to your regular activities gradually.
Eat right. Even though food may not appeal to you, it is important to get adequate nutrition. For most people, nausea and
loss of appetite become worse as the day goes on. Try eating a substantial (but not heavy) meal in the morning and
lighter meals later in the day.
Drink plenty of liquids to avoid dehydration. It is important that you keep your body well-hydrated when you have hepatitis
B, especially if you have been vomiting. Drink plenty of water and, if you can tolerate them, drink fruit juices and broth to
obtain additional calories. Rehydration drinks help replenish electrolytes.
Avoid alcohol and drugs. Hepatitis B makes it difficult for your liver to process drugs and alcohol. If you take drugs
(prescription or illegal) or drink alcohol when you have hepatitis, their effects may be more powerful and may last longer.
Also, alcohol and some drugs can make liver damage worse. You should avoid alcohol until your doctor feels that your
liver is completely healed, which may take as long as 3 to 4 months. Tell your doctor about all of the prescription and
over-the-counter medicines you are taking.
Try to control itching. People with hepatitis B sometimes develop itchy skin. You might try nonprescription medicines, such
as Benadryl or Chlor-Trimeton, to control itching. But talk to your doctor before taking any over-the-countermedicines.
Prevent the spread of HBV by informing people you live with or sleep with about the illness, by not sharing personal
toiletries (such as razors and toothbrushes), and by using a condom or abstaining from sex.

Approach Considerations
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease,
particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC). [4] Risk factors for progression of chronic HBV
include the following[4] :

Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence
of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patients immune response with immunotherapeutic
interventions is needed for the best prognosis.[35] The prevention of HCC often includes the use of antiviral treatment using
pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.[36]
Therapy is currently recommended for patients with evidence of chronic active hepatitis B disease (ie, abnormal
aminotransferase levels, positive HBV DNA findings, positive or negative hepatitis B e antigen [HBeAg]). Various
algorithms have been proposed, such as that by the American Association for the Study of Liver Diseases (AASLD),[47] the
European Association for the Study of the Liver (EASL),[48] the Asian Pacific Association for the Study of the Liver
(APASL),[49]the Canadian Association for the Study of the Liver (CASL),[50] the National Institute for Health and Clinical
Excellence (NICE),[51] Kuo and Gish,[21] and Keeffe et al.[52]
The National Institutes of Health (NIH) recommends nucleos(t)ide therapy for the treatment of patients with acute liver
failure, as well as cirrhotic patients who are HBV DNA positive and those with clinical complications, cirrhosis or advanced
fibrosis with positive serum HBV DNA, or reactivation of chronic HBV during or after chemotherapy or
immunosuppression.[4] In addition, immunoglobulin and vaccination should be administered to newborns born to women
positive for hepatitis B surface antigen (HBsAg).[4, 42, 53]
In general, for HBeAg-positive patients with evidence of chronic HBV disease, treatment is advised when the HBV DNA
level is at or above 20,000 IU/mL (105copies/mL) (or, per the EASL, >2,000 IU/mL[48] ) and when serum alanine
aminotransferase (ALT) is elevated for 3-6 months.[4]
For HBeAg-negative patients with chronic hepatitis B disease, treatment can be administered when the HBV DNA is at or
above 2000 IU/mL (104 copies/mL) and the serum ALT is elevated (ALT levels >20 U/L for females; 30 U/L for males) for
3-6 months.
In patients coinfected with HBV and HIV, initiate therapy against HBV and administer antiretroviral therapy as well. [42]

The NIH also indicates that immediate therapy is not routinely indicated for patients who have the following[4] :

Chronic hepatitis B with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy
(immune-tolerant phase)
Low levels of or no detectable serum HBV DNA and normal serum ALT levels (inactive chronically infected/low
replicative phase)
Positive serum HBV DNA but not HBsAg (latent HBV infection), unless the patient is undergoing immunosuppression

Inpatient care
Patients with hepatitis B disease and fulminant hepatic failure should be hospitalized in the intensive care unit (ICU) and
be considered as liver transplant candidates in the event that they do not recover. Any patient with acute HBV disease
needs to be treated with first-line oral therapy, such as tenofovir disoproxil fumarate (TDF) or entecavir (ETV).
Patients with acute hepatitis should be monitored with blood tests in order to document biochemical improvement (see
Workup).

Dietary limitations
Patients with acute or chronic hepatitis without cirrhosis have no dietary restrictions. For individuals with decompensated
cirrhosis (prominent signs of portal hypertension or encephalopathy), the following dietary limitations are indicated:

A low-sodium diet (1.5 g/day)

High-protein diet (ie, white-meat protein, such as pork, turkey, or fish)
Fluid restriction (1.5 L/day) in cases of hyponatremia