Hepatitis is an acute inflammatory disease of the liver, caused by any
of several viruses. Symptoms include anorexia, nausea, vomiting,
fatigue and
low-grade fever. The liver becomes enlarged and there is discomfort in
the upper-right quadrant of the abdomen. Considerable jaundice occurs
along with dark-colored urine and pale stools. Table: Summary of
the Five Types of Viral Hepatitis Hepatitis A is
caused by Hepatitis A virus (HAV). Hepatitis A can affect
anyone. In the U.S., hepatitis A occurs in situations
ranging from isolated cases of disease to widespread epidemics. Good
personal hygiene and
proper sanitation can help prevent hepatitis A. Vaccines are also
available for long-term prevention of hepatitis A virus infection in
persons 12 months of age and older. Immune globulin is available for
short-term prevention of hepatitis A virus infection in individuals of
all ages.
Hepatitis B is
a serious disease caused by Hepatitis B virus (HBV). Hepatitis B can
cause lifelong infection and serious damage to the liver resulting in
cirrhosis
(scarring) of the liver, liver cancer, liver failure, and death.
Hepatitis B vaccine is
available for all age groups to prevent hepatitis B virus infection. Hepatitis C is
caused by Hepatitis C virus (HCV), which is found in the
blood of persons who have the disease. HCV is spread by contact with
the blood of an infected person.
Hepatitis D is
caused by Hepatitis D virus (HDV), a defective virus
that needs the Hepatitis B virus to exist. HDV is
found in the blood of persons infected with the virus.
Hepatitis E,
caused by the Hepatitis E virus (HEV), is transmitted in much the
same
way as Hepatitis A virus. Hepatitis E, however, does not occur often in
the United States.
Three
viruses, hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis
C virus (HCV) account
for most cases of hepatitis. HAVis a picornavirus, a very small
nonenveloped virus with an ssRNA genome, similar in size and shape to
the poliovirus.
HBV is a dsDNA virus in the
family Hepadnaviridae. Hepadnaviruses have a unique mode of
replication that involves an RNA intermediate as a template for DNA
synthesis.
HCV is in the flavivirus group of small, spheroidal,
enveloped, ssRNA viruses.
Left.
Cartoon of Hepatitis B Virus (HBV). Right. Electron Micrograph of HBV.
Both from Linda Stannard, Department of Medical Microbiology,
University of Cape Town. http://web.uct.ac.za/depts/mmi/stannard/hepb.html. The virus is 42nm
in diameter and possesses an isometric nucleocapsid or "core",
surrounded by an outer coat. The protein of the virus coat is termed
"surface antigen" or HBsAg. It is sometimes extended as a tubular tail
on one side of the virus particle. The surface antigen is generally
produced in vast excess, and is found in the blood of infected
individuals in the form of filamentous and spherical particles.
Filamentous particles are identical to the
virion "tails"; they vary in length and have a mean diameter of about
22nm.
HAV disease or "infectious hepatitis" spreads by
fecal contamination of hands, food and water. It has also been
associated with eating raw shellfish, which concentrate the virus from
polluted sea water.
The incubation period for HAV is usually 15-50 days. Some cases are
severe, requiring weeks of bed rest and recovery, but most are mild and
self-limited, and many are asymptomatic. Many people in the population
have a high level of antibody to HAV which is taken as evidence that
the disease is widespread (one-third of Americans have evidence of past
infection).
Persons at risk of infection include household contacts of infected
persons, sex contacts of infected persons (the virus can be transmitted
sexually), drug users, and persons living or traveling in regions where
Hepatitis A is prevalent.
The best prevention against HAV disease is proper hand washing after
using the bathroom, changing a diaper, and before preparing and eating
food. HAV is very infectious, so that food handlers and restaurant
workers should always wash their hands after use of the bathroom.
Hepatitis A vaccine provides life-long protection against the disease.
Short term protection against hepatitis A is available from immune
globulin. It can be given before and within two weeks after coming in
contact with HAV. Passive immunity is not long-lasting, however.
The HAV vaccine consists of inactivated virus. Two doses of vaccine,
given six months apart, are needed for lasting protection. The
vaccine may be given whenever a person is at risk of infection. It is
recommended for persons 12 months of age and older if they are
street-drug users, men having sex with men, persons with blood clotting
disorders or chronic liver disease, and children, workers or travelers
in areas of increased rates of hepatitis A.
HBV disease is sometimes called
"serum hepatitis", because it
is principally transmitted by blood and blood products. Minute amounts
of infected blood (0.0001 ml) injected or rubbed into minor wounds can
be effective in transmitting the virus. HBV is spread through having
sex with an infected person without using a condom, by sharing
drugs or needles when shooting drugs, through needle sticks or sharps
exposures on the job, and from an infected mother to her baby during
birth. Some of the ways that HBV has been spread are by blood
transfusions, shared needles by drug users, tattooing and body
piercing,
shared toothbrushes, razors and towels.
Hepatitis caused by HBV tends to be more severe than that caused by
HAV. While some infections may be inapparent, overall, it has a
mortality rate between 1% and 10%. The number of new infections per
year in the United States has declined from an average of 260,000 in
the 1980s to about 73,000 in 2003. The hepatitis B vaccine has been
available since 1982.
HBV has an incubation period of 43 -180 days. The virus does not cause
a cytopathic effect on the liver, and damage to the liver is thought to
result from an immune response against viral-induced cellular antigens.
In most patients, the virus disappears from the blood during the latter
part of the infection, but in a few it may persist and circulate for
months or years. It is estimated that there are 1.25 million carriers
in the United States. Sometimes, the concentration of virus particles
in
the serum is 1013-1014 per ml, although only
relatively few of the particles contain DNA.
About 30% of infected persons have no signs or symptoms. Signs and
symptoms are less common in children than adults. Chronic infection
occurs in 90% of infants infected at birth, 30% of children infected at
age 1-5 years, and 6% of persons infected after age 5 years. Death from
chronic liver disease occurs in 15-25% of chronically-infected persons.
Adefovir dipivoxil, interferon alfa-2b, pegylated interferon
alfa-2a, lamivudine, and entecavir are five drugs used for the
treatment of persons with chronic hepatitis B.
Hepatitis B vaccine has been available since 1982. Use of the vaccine
has resulted in a greater than three-fold reduction in the number of
new cases since that time. CDC recommends routine vaccination for
persons under 18 years age or members of risk groups of any age. Risk
groups include persons with multiple sex partners, men who have sex
with men, sex contacts of infected persons, injection drug users, and
household contacts of chronically infected persons.
The recombinant vaccines that are licensed for use in the United States
are synthesized by Saccharomyces
cerevisiae (baker's yeast), into which
a plasmid containing the HBsAg has been inserted. Purified HBsAg is
obtained by lysing the yeast cells and separating HBsAg from the yeast
components. Persons allergic to yeast should be vaccinated with
vaccines containing yeast.
HCV disease is another type of
serum hepatitis inasmuch as, like HBV, it is transmitted by blood and
blood products. In fact, persons at risk for HVC hepatitis might be at
risk for infection by HBV (as well as HIV). Transmission occurs when
blood from an infected person enters the body of a person who is not
infected. HCV is spread through sharing needles when shooting drugs,
through needle sticks or sharps exposures on the job, or from an
infected mother to her baby during birth. HCV can be spread by sex, but
this is rare. Most infections are due to illegal injection drug use.
HCV infection is the leading indication for liver transplant.
An estimated 3.9 million (1.8%) Americans have been infected with HCV,
of whom 2.7 million are chronically infected. Chronic infection occurs
in 55-85% of the infected persons. Chronic liver disease occurs in 70%
of
chronically-infected persons and accounts for a 1-5% mortality rate
among infected persons.
HCV-positive persons should be evaluated for liver disease. Interferon
and ribavirin are two drugs licensed for treatment of persons with
chronic hepatitis C. Interferon can be taken alone or in combination
with ribavirin. Combination therapy using pegylated interferon and
ribaviran is currently the treatment of choice. Combination therapy can
eliminate the virus in 50% of persons infected with HCV genotype 1, and
up to 80% of individuals infected with HCV genotypes 2 and 3.
