Hepatitis-B: A Review
Arti Mohan
Integrated Institute of Technology, Dwarka, New Delhi.
INTRODUCTION:
Hepatitis implies injury to liver characterized by the presence of
inflammatory cells in the tissue
of the organ. The name is from ancient Greek hepar , the root being hepat-
meaning liver, and suffix -itis, meaning "inflammation"
The condition can be self-limiting, healing on its own, or can progress to
scarring of the liver. Hepatitis is acute
when it lasts less than six months and chronic when it persists longer. A group
of viruses known as the hepatitis viruses cause most cases of liver damage
worldwide. Hepatitis can also be due to toxins (notably alcohol), other
infections or from autoimmune process. It may run a sub clinical
course when the affected person may not feel ill. The patient becomes unwell
and symptomatic when the disease impairs liver functions that include, among
other things, removal of harmful substances, regulation of blood composition,
and production of bile to help digestion. Hepatitis
B is a
disease caused by hepatitis B virus which infects the liver of hominoidae,
including humans, and causes an inflammation called hepatitis. Originally known
as "serum hepatitisth” (1)
disease has caused epidemics in parts of Asia and Africa, and it is endemic in
China. About a third of the world’s population, more than 2 billion people have
been infected with the hepatitis B virus. This includes 350 million chronic
carriers of the virus. Transmission of hepatitis B virus results from exposure
to infectious blood or body fluids containing blood.
History:
The earliest
record of an epidemic caused by Hepatitis B virus was made by Lurman in 1885.
An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees
were vaccinated
with lymph
from other people. After several weeks, and up to eight months later, 191 of
the vaccinated workers became ill with jaundice
and were diagnosed as suffering from serum hepatitis. Other employees who had
been inoculated with different batches of lymph remained healthy. Lurman's
paper, now regarded as a classical example of an epidemiological
study, proved that contaminated lymph was the source of the outbreak. Later,
numerous similar outbreaks were reported following the introduction, in 1909,
of hypodermic needles
that were used, and more importantly reused, for administering Salvarsan
for the treatment of syphilis.
The virus was not discovered until 1965 when Baruch Blumberg, then working at the National Institutes of
Health
(NIH), discovered the Australia antigen
(later known to be Hepatitis B surface antigen, or HBsAg) in the blood of
Australian aboriginal people. Although a virus had been suspected since the
research published by MacCallum in 1947, D.S. Dane and others discovered the virus
particle in 1970 by electron microscopy.
By the early 1980s the genome
of the virus had been sequenced, and the first vaccines were being tested.
Hepatitis B virus is an hepadnavirus—hepa
from hepatotrophic and dna because it is a DNA virus) and it has a circular genome composed
of partially double-stranded DNA. The viruses replicate through an RNA intermediate form by
reverse transcription, and in this respect they are similar to retroviruses.
Although replication takes
place in the liver, the virus spreads to the blood where virus-specific
proteins and their corresponding antibodies are found in infected people. Bloods test for these
proteins and antibodies are used to diagnose the infection.
Pathogenesis:
Cirrhosis of the
liver and liver cancer may ensue from Hepatitis B.The
hepatitis B virus primarily interferes with the functions of the liver by
replicating in liver cells, known as hepatocytes.During
HBV infection, the host immune response causes both hepatocellular
damage and viral clearance. Although the innate immune response does not play a
significant role in these processes, the adaptive immune response, particularly
virus-specific cytotoxic T lymphocytes (CTLs), contributes to
most of the liver injury associated with HBV infection. By killing infected
cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, CTLs
eliminate the virus (2). 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.
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, dark urine, and then progresses to
development of jaundice.
It has been noted that itchy skin has been an indication as a possible symptom
of all hepatitis virus types. The illness lasts for a few weeks and then
gradually improves in most affected people. A few patients may have more severe
liver disease (fulminant hepatic failure), and may die as
a result of it. The infection may be entirely asymptomatic and may go
unrecognized.
Chronic infection with Hepatitis B
virus may be either asymptomatic or may be associated with a chronic
inflammation of the liver (chronic hepatitis), leading to cirrhosis
over a period of several years. This type of infection dramatically increases
the incidence of hepatocellular carcinoma (liver cancer).
Chronic carriers are encouraged to avoid consuming alcohol as it increases
their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked
to the development of Membranous glomerulonephritis (MGN
·
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 involve serum
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(3).
The hepatitis B surface antigen (HBsAg) is most frequently used to
screen for the presence of this infection. It is the first detectable viral antigen
to appear during infection. However, early in an infection, this antigen may
not be present and it may be undetectable later in the infection as it is being
cleared by the host. The infectious virion contains an inner "core
particle" enclosing viral genome. The icosahedral core particle is made of
180 or 240 copies of core protein, alternatively known as hepatitis B core
antigen, or HBcAg. During this 'window' in which the host remains
infected but is successfully clearing the virus, IgM antibodies to the
hepatitis B core antigen (anti-HBc IgM) may be the only serological
evidence of disease.
Shortly after the appearance of
the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will
appear. Traditionally, the presence of HBeAg in a host's serum is associated
with much higher rates of viral replication and enhanced infectivity; however,
variants of the hepatitis B virus do not produce the 'e' antigen, so this rule
does not always hold true. During the natural course of an infection, the HBeAg
may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise
immediately afterwards. This conversion is usually associated with a dramatic
decline in viral replication.
If the host is able to clear the
infection, eventually the HBsAg will become undetectable and will be followed
by IgG antibodies to
the hepatitis B surface antigen and core antigen, (anti-HBs and anti
HBc IgG). A person negative for HBsAg but positive for anti-HBs have either
cleared an infection or has been vaccinated previously.
Individuals who remain HBsAg
positive for at least six months are considered to be hepatitis B carriers.
Carriers of the virus may have chronic hepatitis B, which would be reflected by
elevated serum alanine aminotransferase levels and
inflammation of the liver, as revealed by biopsy. Carriers who have
seroconverted to HBeAg negative status, particularly those who acquired the
infection as adults, have very little viral multiplication and hence may be at
little risk of long-term complications or of transmitting infection to others.
More recently, PCR
(Polymerase Chain Reaction) tests have been developed to detect and measure the
amount of viral nucleic acid in clinical specimens. These tests are called viral loads
and are used to assess a person's infection status and to monitor treatment.
Prognosis:
Hepatitis B virus infection may
either be acute (self-limiting) or chronic (long-standing). Persons with
self-limiting infection clear the infection spontaneously within weeks to
months.
Children are less likely than
adults to clear the infection. More than 95% of people who become infected as
adults or older children will stage a full recovery and develop protective
immunity to the virus. However, only 5% of newborns that acquire the infection
from their mother at birth will clear the infection. This population has a 40%
lifetime risk of death from cirrhosis or hepatocellular carcinoma (4).
Of those infected between the ages of one to six, 70% will clear the infection.
Hepatitis D
infection can only occur with a concomitant infection with Hepatitis B virus
because the Hepatitis D virus uses the Hepatitis B virus surface antigen to
form a capsid. Co-infection with hepatitis D increases the risk of liver
cirrhosis and liver cancer.
Treatment:
Acute hepatitis B infection does
not usually require treatment because most adults clear the infection spontaneously
(5). Early antiviral
treatment may only be required in less than 1% of patients, whose infection
takes a very aggressive course ("fulminant hepatitis") or who are immunocompromised.
On the other hand, treatment of chronic infection may be necessary to reduce
the risk of cirrhosis and liver cancer. Chronically infected individuals with
persistently elevated serum alanine aminotransferase, a marker of liver
damage, and HBV DNA levels are candidates for therapy. There are four
medications currently approved by the Food and Drug administration (FDA) for
treatment of acute hepatitis B infection.
1. Alfa Interferon (Brand
names: INTRON A, INFERGEN, ROFERON): Interferon is an antiviral agent with
antiproliferative and immunomodulatory agent that is administered by
subcutaneous injection daily or three times per week, for 12-16 weeks or
longer. With adequate teachings, the injections can be easily administered at
home by patients. High pretreatment ALT and lower levels of HBV DNA are the
most important predictors of response to alfa interferon therapy. Virologic
response to alfa interferon occurs in less than 10% of patients with normal
ALT. A sustained response can be seen in 15-30% of patients with HbeAg-negative
chronic hepatitis B and less than half of the patients show sustained clearance
of HbsAg.
2. Lamivudine (Epivir-HBV,
3TC): inhibits hepatitis B viral DNA synthesis. It should be taken orally once
daily. It is approved for use in adults and children and is usually well
tolerated. While Lamivudine benefits patients with HbeAg-negative chronic
hepatitis B, a vast majority of patients relapse once the treatment is stopped.
3. Adefovir dipivoxil
(Hepsera): inhibits DNA polymerase activity and reverse transcriptase.This drug
is administered orally on a daily basis and is well tolerated. It can be
associated with kidney dysfunction, particularly if used in high doses.
4. Baraclude (Entecavir): is
the latest drug approved by FDA for the treatment of chronic Hepatitis B. It
works by inhibiting the function of hepatitis B virus polymerase.Side effects
include headache, fatigue, dizziness, nausea and temporary elevation of liver
enzymes. This drug is taken orally once daily.
In patients with severe
liver dysfunction, a liver transplant may be required.
Prevention of Hepatitis B:
Current public health efforts to
prevent the disease have focused on vaccinating people in high risk groups
especially all children and adolescents.
Those at greater risk are:
intravenous drug abusers, heterosexuals with multiple partners, homosexual men,
health care worker and children born to immigrant from China, South East Asia
and either place where Hepatitis B is very common.
Three doses of vaccine are
required to achieve effective immunization and will induce adequate antibody in
80- 95% of the patients who get three doses. The vaccination schedule most
often used is three intramuscular injections, with the second and third doses
administered at 1-6 months after the first.
The first dose of Hepatitis B
vaccine is given soon after birth before the infant is discharged from the
hospital or in the first two months of life. The second dose is given between
one or two months after the first and the third at 6-18 months of age. Since
1999, two dose vaccines are available and required in some cases for
adolescents age 11 to 15 years.
Infants born to mothers infected
with hepatitis B virus should be treated with hepatitis B immune globulin and
hepatitis B vaccine within 12 months of birth, with the second and third doses
of vaccine given at one and six months of age.
Adults and other children should
receive the injections in the deltoid. Infants should receive the injections in
the thigh. Buttock injection should never be used.
Patient Education:
Other means of prevention include
educating the patients about:
·
(If carrier) cover open wounds, don’t share razors or manicure tools.
·
Practice safe sex
·
Don’t share needles, razors, toothbrushes, manicure tools or other items
that could bear contaminated blood.
Don’t allow you to be pierced or
tattooed with non-sterile equipment.
·
Limit alcohol intake.
·
Never share IV drug needles or other drug equipment
REFERENCES:
1) Online Etymology Dictionary
2)
“HBV
pathogenesis in animal models: recent advances on the role of platelets”.
Iannacone M, Sitia G, Ruggeri ZM, Guidotti LG
J. Hepatol(2007), 46 (4): 719–26.
3)
"Serological
markers of HBV infectivity". Bonino F, Chiaberge E, Maran E, Piantino P ;Ann.
Ist. Super. Sanita (1987),24 (2): 217–23
4)
"Hepatitis B Virus Infection". Dienstag JL; New England Journal of Medicine(2008), 359
(14): 1486–1500.
5) "Hepatitis B: the pathway to recovery through
treatment". Hollinger
FB, Lau DT; Gastroenterol.
Clin. North Am. (2006), 35 (4): 895–931
Received on 10.11.2009
Accepted on 12.02.2010
© A&V Publication all right reserved
Research J. Pharmacology and
Pharmacodynamics 2(2): March –April 2010: 165- 167
