Hepatitis A or Hepatitis E?
AM Report 5/19/09
Anne Peery MD
Hepatitis A
Pathophysiology
 HAV is a small non-enveloped RNA hepatovirus
 HAV is exclusively a virus of humans and primates
 Transmitted by the fecal-oral route
 Absorbed in the small intestine and replicates in the liver
 HAV is secreted in the bile and shed in feces for 1-2 weeks
BEFORE clinical illness and approximately 1 week after
the onset
 Incubation period is 15-50 days (on average 30 days)
 There is NO chronic carrier state
Hepatitis A
Epidemiology
 Transmitted by the fecal-oral route
 The largest known modern epidemic of hepatitis A was from
consumption of contaminated seafood. In Shanghai, China,
292,301 cases of acute hepatitis were attributed to eating
raw clams
 Spread of hepatitis A has been reported in the United States
and Europe following consumption of contaminated lettuce,
ice slush beverages, frozen strawberries, and salad food
items
 The virus is hardy, surviving on human hands and inanimate
objects (fomites) . Transmission of hepatitis A from
hospitalized patients with unsuspected disease to staff is
well recognized
Hepatitis A
Epidemiology
 Prevalent in the economically developing regions of
Africa, Asia and Latin America where seroprevalence rates
approach 100% and most infections occurs by age 5
 Infection confers lifelong immunity
 Seroprevalence rates are approximately 33% in the US
 Rates of HAV have been decreasing over past 20yrs
secondary use of vaccine and improvements in hygiene,
sewage disposal and food safety
Hepatitis A
Clinical Presentation
 Often asymtomatic in children
 May begin with nonspecific prodrome of fever, malaise,
weakness, anorexia, nausea, vomitting, arthralgias,
mylagias and upper respiratory symptoms
 This is followed by 1-2 wks dark urine, jaundice, mild
pruritus and slight liver enlargement and tenderness
 Labs reflect hepatocellular injury and aminotransferase
levels may be elevated between 500 and 5000; serum
bilirubin usually peaks later then transaminase levels but
usually remains less then 10mg/dl
 Most patients have normalization of LFTs within 6 months
Hepatitis A
Relapsing hepatitis A
 Recurrent hepatitis secondary to primary infection
 The severity of symptoms and biochemical abnormalities
during second phase tend to be the same as observed
during the initial illness except for a tendency to greater
cholestasis
 The rate of hepatitis A relapse varies in different case
series from 1.5% to 11.9%
Hepatitis A
Diagnosis
 Diagnosis requires presence of serum HAV IgM; IgM
antibody persists for 3-6 months after onset of symptoms
Hepatitis A
Differential diagnosis
(Mild transaminitis < 5x nl)

Hepatic: ALT predominant
 Chronic hepatitis C
 Chronic hepatitis B
 Acute viral hepatitis (A-E, EBV,
CMV)
 Steatosis/steatohepatitis
 Hemachromatosis
 Medications/toxins
 Autoimmune hepatitis
 Alpha1-antitrypsin deficiency
 Wilson’s disease
 Celiac disease


Hepatic: AST predominant
 Alcohol-related liver injury
 Steatosis/steatohepatitis
 Cirrhosis
Nonhepatic
 Hemolysis
 Myopathy
 Thyroid disease
 Strenuous exercise
Hepatitis A
Differential diagnosis (Severe transaminitis > 15x nl)
 Acute viral hepatitis (A-E, herpes)
 Medications/toxins
 Ischemic hepatitis
 Autoimmune hepatitis
 Wilson’s disease
 Acute bile duct obstruction
 Acute Budd-Chiari syndrome
 Hepatic artery ligation
Hepatitis A
Treatment
 There is no treatment
Prognosis
 HAV is usually a benign course in young, healthy people
and is associated with a low mortality
 Older adults, immunosuppresed patients and those with
chronic liver disease have greater morbidity and mortality
 Mortality 0.1-2%
Hepatitis A
Prevention


Immune globulin (IG)
 Available since 1940
 Immunoglobins administered low dose provides
protection for 1-2 months
Inactivated HAV vaccine
 Available since 1992
Hepatitis A
Post exposure prophylaxis

Close personal contacts
 Household and sex contacts
 Persons who have shared illicit drugs with someone with
hepatitis A
 Child-care center staff, attendees, and attendees'
household members
 Persons exposed to a common source, such as an infected
food handler. If a food handler receives a diagnosis of
hepatitis A, PEP should be administered to other food
handlers at the same establishment.
Hepatitis A
Post exposure prophylaxis

Until recently, immune globulin (IG) was the only recommended way to protect
people after they have been exposed to hepatitis A virus.

In June 2007, U.S. guidelines were revised to allow for hepatitis A vaccine to be
used after exposure to prevent infection in healthy persons aged 1–40 years.

Healthy persons aged 12 months – 40 years, who have recently been exposed to
HAV and who have not been vaccinated previously should be administered a single
dose of hepatitis A vaccine, within 2 weeks after exposure.

For persons aged >40 years, IG is preferred because of the absence of information
regarding vaccine performance in this age group and because of the more severe
manifestations of hepatitis A in older adults. Vaccine can be used if IG cannot be
obtained.

For children aged <12 months, immunocompromised persons, persons with chronic
liver disease, and persons who are allergic to the vaccine or a vaccine component,
IG should be used.
Hepatitis A
Prevention
 Pre exposure prophylaxis

Indications for HAV vaccination:

People planning to travel to endemic areas





The risk for hepatitis A exists even for travelers to urban areas, those who
stay in luxury hotels, and those who report that they have good hygiene
and that they are careful about what they drink and eat
Men who have sex with men
Illicit drug users
People with chronic liver disease
Recipients of clotting factor concentrates
Hepatitis A
Prevention
 Advisory Committee on Immunization Practices (ACIP)
recommends one dose of single-antigen hepatitis A
vaccine administered at any time before departure may
provide adequate protection for most healthy persons.
 For optimal protection, older adults,
immunocompromised persons, and persons with chronic
liver disease or other chronic medical conditions who are
planning to depart in <2 weeks should receive the initial
dose of vaccine and also can simultaneously be
administered IG (0.02 mL/kg) at a separate anatomic
injection site.
Hepatitis E
Pathophysiology
 HEV is a small non-enveloped single strain RNA virus
 HEV can infect humans, primates, swine
 Transmitted by the fecal-oral route; thought to spread
zoonotically (principally through swine)
 Absorbed in the small intestine and replicates in the liver
 HAV is secreted in the bile and shed in feces for 1-2 weeks
BEFORE clinical illness and approximately 1 week after
the onset
 Incubation period is on average 40 days
 There is NO chronic carrier state
Hepatitis E
Epidemiology
 First recognized as a disease in 1980
 Considered most important or second most important
cause of acute clinical hepatitis in adults throughout Asia,
Middle East and Africa
 Rare in industrialized countries but antibody is found
worldwide
 Diagnostic tests vary greatly in specificity, sensitivity, and
availabilty
 Hepatitis E is probably underdiagnosed
 Fewer then a dozen cases have been reported in the US
Hepatitis E
Clinical Presentation
 Similar to HAV
 Relapsing hepatitis is rare
Diagnosis
 Diagnosis requires presence of serum HEV IgM
 Mayo send out $123.90
Hepatitis E
Prognosis
 Self limited disease
 Mortality 1-4%
 Mortality is approximately 20% in pregnant women
 Transmission of HEV from pregnant mother to fetus can
result in fetal demise
Hepatitis E
Treatment
 No treatment available
Prevention
 GlaxoSmithKline has developed a HEV vaccine
 Double blind study 2000 adults 95.5% efficacious and
minimal adverse events
 The vaccine is not commercially available