VIRAL HEPATITIS Part I: Focus
On The Enterically-Transmitted Forms
The causes of hepatitis, or
inflammation of the liver, range from bacterial, fungal, or viral
infection; parasitic infestation; drug reactions; and toxins to
autoimmune and genetic disorders. Common viral causes include yellow
fever virus, Epstein-Barr virus, and cytomegalovirus; but the term
“viral hepatitis” is usually reserved for infection by one or
more of five hepatitis viruses A, B, C, D, and E, recognized as major
public health problems worldwide.1,2 Acute infection by any of these
viruses can present similarly, and victims are often totally
asymptomatic, which supports the assumption that vast numbers of
cases go undiagnosed and unreported. Symptoms can be mild and vague,
as a flu-like syndrome, or more acute and specific, progressing to
total hepatic failure, coma, and death.2 Presentation depends not only on the
causative virus, but on the phase of the disease in which the patient
finds himself. Phase 1, characterized by viral
replication, is frequently asymptomatic, detection possible only via
enzymatic and serologic means
Phase 2, or the prodromal phase,
often shows up with symptoms of respiratory viral illness or
gastroenteritis, with low-grade fever, nausea and vomiting, anorexia,
alterations in taste, arthralgia, fatigue, malaise, urticaria, and
pruritus. Aversion to tobacco smoke is a common finding at this
stage.
Phase 3, the icteric phase, is
commonly characterized by classic symptoms of impaired hepatic
function, with darkened urine and pale feces noted. Malaise and
gastrointestinal symptoms may be more pronounced and severe at this
stage, often leading to some degree of dehydration that must also be
addressed. Jaundice, hepatomegaly, and pain in the right upper
quadrant are common at this stage.
Phase 4, the convalescent phase,
sees jaundice and other symptoms resolve, with liver function
returning to normal.
COMMON SYMPTOMATOLOGY2,4,5,6
* Fatigue
* General discomfort or malaise
* Depression
* Generalized urticaria
* Low-grade fever
* Arthralgia, myalgia
* Headache
* Dyspepsia
* Anorexia
* Abnormal taste
* Nosebleed
* Nausea and vomiting
* Abdominal fullness, gas
* Abdominal distension
* Pale or clay-colored stools
* Diarrhea
* Jaundice
* Hepatomegaly
* Dark urine
* Bad breath
* Point tenderness
* Gynecomastia
In spite of
similar clinical presentation and similarities among various subsets
of these viruses in pathophysiology and epidemiology, a number of
significant differences make them unique entities, differing in
clinical course, treatment options, and prognosis.
The Jargon
Hepatitis has long been classified
into two primary categories according to epidemiology: Infectious,
or enterically-transmitted, spread via the fecal-oral route from
person to person; and serum, or parenterally-transmitted,
spread via transfusion of blood or blood products. In the 1960s and
1970s, technological advances allowed laboratory identification and
differentiation of hepatitis A virus (HAV) and hepatitis B virus
(HBV), the predominant etiologic agents responsible for infectious
and serum hepatitis, respectively.4
In 1977, hepatitis D virus (HDV) was
identified and discovered to be a defective, or incomplete virus
incapable of replication and incapable of causing infection in the
absence of HBV. Viral hepatitis without the serologic markers of
these identified viruses was then classified as either
parenterally-transmitted non-A, non-B hepatitis or
enterically-transmitted non-A, non-B hepatitis.5 Over the past ten years, hepatitis C
virus (HCV) has been identified as the primary cause of
parenterally-transmitted non-A, non-B hepatitis; and hepatitis E
virus (HEV) has been identified as the primary causative agent in
enterically-transmitted non-A, non-B hepatitis. The process of
classification via serologic assay continues, as non-ABCDE hepatitis
have been recognized.5
Enterically-Transmitted
Forms Hepatitis A (HAV) and E (HEV)
With feces the
major source of virus in both cases, hepatitis A and E are both
transmitted primarily via the fecal-oral route, excreted in the feces
of infected individuals for about 14 days after illness onset.
Viremia with both is transient, so they are only rarely transmitted
parenterally. They are commonly found in water contaminated by raw
sewage as well as shellfish living in those waters. They are
acid-stable, surviving assault by the acid environment of the
gastrointestinal system and surviving for hours on fomites and the
skin. HVA has been known to survive in water for up to 10 months.
Transmission of HAV is common from infected individuals, especially
those handling food after cooking and among people in close contact
and/or questionable sanitary conditions as in penal institutions,
mental institutions, and even day care environments. Both are less
common in the developed countries, with incidence much higher in
developing countries and among those who travel to them.1,5
In the absence of
complications, both HAV and HEV normally cause only acute,
self-limiting illness as opposed to chronic disease seen with HBV,
HCV, and HDV. HAV is a hardier, more successful virus, so HAV
infection is far more common, affecting mostly children and young
adults. In spite of its relatively high incidence of some 200,000
cases yearly in the U.S., it is responsible for only about a hundred
deaths each year. It is suspected from immunoassays that as many as
40% of HAV cases are asymptomatic and go completely undetected,
facilitating its spread.2,6
HEV is more
exclusively associated with contaminated drinking water, almost all
cases of HEV reported in the United States having occurred among
travelers returning from endemic areas. It is most often seen in
young adults and pregnant women, and it is associated with a high
mortality rate among pregnant women during the third trimester.
Both are associated with cyclical epidemic patterns. Incubation for
HAV is 15 to 50 days, averaging 28 days, while that for HEV is 15 to
60 days, averaging 40 days. HAV infection, though not cytopathic
itself, elicits a cell-mediated immune response responsible the
hepatopathology observed with disease.3,4,6
Diagnosis While elevations in ALT, AST, GPT, and
creatine phosphokinase are not uncommon, they in no way aid in
differential diagnosis of the particular offending virus. Assessment
of symptoms listed above and screening for high-risk behaviors in any
suspected hepatitis are essential, so the following questions can be
helpful in diagnosis.3,5
* Do you drink alcohol?
* Have you engaged in unprotected
sex?
* Have you used injectable drugs?
* Have you recently eaten shellfish?
* Have you been in contact with
anyone who might have had hepatitis?
* Have you traveled in developing
countries?
Serologic
detection of anti-HAV is diagnostic, though detection methods for
anti-HEV are not yet widely available. Antibody titers, both IgM and
IgG, follow predictable curves with both infections. The viruses
themselves can be detected in the stool up until about 2 weeks after
symptoms appear, and a stool sample can help to rule out bacterial or
parasitic causes. Abdominal ultrasound examination or CT scan, or
even liver biopsy may be occasionally necessary in severe,
refractory, or recurrent disease to assess extent and causes of liver
damage.2,5
Treatment and Prevention In the persisting absence of specific
therapy, treatment for both infections is merely supportive, with
rest and avoidance of other types of hepatic insult like alcohol and
potentially problematic medications during the acute phase. Frequent
smaller meals and ample fluid intake are also generally encouraged.
Prevention of spread for both consists of ensuring adequate hygiene,
particularly for those handling food or necessarily in close
proximity to suspected infectees, and avoidance of potentially
contaminated food or water (this includes swimming in contaminated
pools or lakes). During epidemics of HAV in this country and when
traveling to endemic areas, all effort should be made to avoid
contact with potentially contaminated water, as even tap water in
this country can be suspect during periods of high infection. Avoid
uncooked foods that may have been washed in suspect water or handled
by infected persons and ice made from suspect water. Use only
bottled water for brushing teeth, and remember that HAV can survive
for several hours on the skin after washing with contaminated water.
HAV can be inactivated by exposure to heat above 85 degrees C. for
one minute.1,2,3,4,6
For HEV, avoidance is the only
available protection, as efforts to prevent infection with immune
globulin and vaccination have proved futile. For HAV, though, those
with known exposure -- household contacts, sexual contacts, day care
co-attendees and staff, caregivers, and even patrons of restaurants
when infected food handlers are discovered – can be given
intramuscular immune globulin (IG) in doses of 0.02mg/kg. Such IG
postexposure prophylaxis has been shown effective for 85% of exposed
individuals when administered within 2 weeks of exposure.1,6
IG can also be
used as pre-exposure prophylaxis, but passive protection is generally
limited to a maximum of 3 to 5 weeks. Prophylaxis by vaccination to
produce active immunity to HAV approaches 100% efficacy and immunity
is expected to last for about 20 years. Most HAV infections in the
this country occur during extended community-wide outbreaks, where
many victims have no identifiable risk factors, the highest incidence
among children 5 to 14 years of age who transmit it to adults.
Travelers to developing countries, homosexual or bisexual men, and
injectable drug users are at particular risk of contracting HAV
infection.3,5
Available HAV
Vaccines Dose Havrix * Adults
over age 18 1cc (1440 EL U) IM with booster in 6 to 12 months
* Ages 2 to 18 0.5cc
(720 EL U) IM with booster in 6 to 12 months
Vaqta * Adults
18 or over 0.5cc (50U) IM with booster in 6 months
* Ages 2 to
17 0.25cc(25U) IM with booster in 6 months5,7
The initial dose of either vaccine
should be administered at least 2 weeks before anticipated exposure,
but concurrent IG can be given to cover exposure during that 2-week
period. The ultimate antibody titer in response to the combination
may be lower than that produced by giving the vaccine alone.
Simultaneous administration with hepatitis B vaccine produces
acceptable immune response to both, and concomitant administration of
other vaccines or IG requires different syringes and injection
sites.7
Immunocompromised patients may not
achieve an immune response sufficient to prevent infection with the
initial dose, so additional doses may be necessary; and unless
potential benefit of immediate administration is high, vaccination
should usually be delayed in the presence of febrile illness.7
Conclusion Though seldom lethal in themselves,
both HAV and HEV infection can be fatal in certain populations and
must be taken seriously. Both viruses cause only acute illness in
contrast to the blood-borne viruses that can cause both acute and
chronic illness. Both follow epidemic cycles and are transmitted via
the fecal-oral route, primarily via contaminated water or food. HEV,
the less hardy virus, is transmitted almost exclusively via
contaminated water and is rarely seen in the United States, while HAV
is not uncommon in this country, frequently transmitted by infected
food handlers who may be asymptomatic. Neither infection is
treatable except supportively, so prevention is of paramount
importance, with vaccination and HIG for HAV, but only by avoidance
in the case of HEV.
