Hepatitis A or Hepatitis E?

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Hepatitis A or Hepatitis E?

• AM Report 5/19/09
• Anne Peery MD

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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

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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

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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

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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

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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

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Hepatitis A

• Diagnosis
• Diagnosis requires presence of serum HAV IgM IgM
  antibody persists for 3-6 months after onset of
  symptoms

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Hepatitis A

• Differential diagnosis
• (Mild transaminitis lt 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
• Wilsons disease
• Celiac disease

• Hepatic AST predominant
• Alcohol-related liver injury
• Steatosis/steatohepatitis
• Cirrhosis
• Nonhepatic
• Hemolysis
• Myopathy
• Thyroid disease
• Strenuous exercise

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Hepatitis A

• Differential diagnosis (Severe transaminitis gt
  15x nl)
• Acute viral hepatitis (A-E, herpes)
• Medications/toxins
• Ischemic hepatitis
• Autoimmune hepatitis
• Wilsons disease
• Acute bile duct obstruction
• Acute Budd-Chiari syndrome
• Hepatic artery ligation

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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

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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

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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.

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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 140 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 gt40 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 lt12 months, immunocompromised
  persons, persons with chronic liver disease, and
  persons who are allergic to the vaccine or a
  vaccine component, IG should be used.

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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

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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 lt2 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.

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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

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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

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Hepatitis E

• Clinical Presentation
• Similar to HAV
• Relapsing hepatitis is rare
• Diagnosis
• Diagnosis requires presence of serum HEV IgM
• Mayo send out 123.90

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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

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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