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 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  T he 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