Issues Related to the Outbreaks
Since 1996, children in the United States have been offered the vaccine as part of their immunization schedule. However, there are substantial number of adults born before 1996 who have never been immunized against HAV.2 This makes them extremely susceptible to the infection, which in turn can lead them to also infect others.
Travel to HAV endemic countries by those who are unimmunized against HAV, poses a risk for contracting the infection. Between 2005-2007, 46% of HAV infections were potentially caused by travel outside of the US and Canada.2 HAV is endemic is some areas of Central America and South America, the Middle East, Africa, Asia and the Western Pacific.1 Travel is a popular form of recreation, and access to exotic locations has become easier. However, enhanced detailed HAV surveillance programs have proven to be a difficult undertaking due to either poor reporting or false-positive anti-HAV immunoglobulin M (IgM) findings in those with non-acute liver problems. Even with inconsistent HAV reporting, the Centers for Disease Control and Prevention (CDC) considers international travel to HAV endemic areas to be an important risk factor for HAV.
High-risk sexual behavior can also lead to the spread of HAV. In June 2017, 1,731 patients in 15 European countries were diagnosed with HAV, most of these diagnoses being in MSM.3 In the United States, HAV has been reported in the MSM populations of urban cities across the country. In 2018, the CDC estimated that 10% of new HAV cases in the United States occur in the MSM population, an increase from 4.9% in 2010.1,4
From 2017 to early 2018, San Diego, California, had an outbreak of 587 reported cases of HAV, which resulted in 402 hospitalizations and 20 deaths.5 Although there have been other reported HAV outbreaks, this was the largest HAV outbreak in the United States in 2 decades.5 By April 2018, the CDC had received more than 2500 reports of HAV from multiple states.5 The San Diego outbreak, as with most of these reported sites, have been mostly associated with the homeless population and illicit drug users in settings with limited sanitation. These outbreaks were a reminder that HAV, in certain populations, could result in increased morbidity and mortality.
Up until the development of the HAV vaccine, HAV was treated by stressing improved hygiene and sanitation, and by providing passive immunity by the administration of immune globulin (IG). However, since there is a decreased prevalence of previous HAV infections in plasma donors, the dosage for IG has recently been increased to provide enough HAV IgG antibodies for protection. Providers who are not updated on this information, may be providing insufficient dosing against HAV.
Transmission and Incubation
HAV is spread from person to person through the fecal-oral route. Hepatic replication of the virus is detectable in the blood and eventually excreted in the feces by days 10-12 post-exposure.1 Feces from an infected person, which is then spread to food and water through poor handwashing or inadequate hygiene, is the main source of transmission of the virus.6 Incubation of the virus in the human body can take anywhere from 15-50 days.1
Clinical presentation and diagnosis
70% of adolescents and adults will show some signs of clinical illness, such as jaundice.1 The majority of children under 6 years of age are asymptomatic and can shed the virus 10 weeks longer than adults, which makes them a high risk for spreading the infection.1,7
Signs and symptoms of HAV can last as long as 2 months. Symptoms include jaundice, nausea, vomiting, fever, malaise, anorexia, abdominal pain, dark urine, pale stools and pruritus. Physical exam usually reveals hepatomegaly and jaundice. In the acute phase, laboratory testing will show elevated liver enzymes and a positive anti-HAV IgM. If the patient has already had the infection or had the HAV vaccine, then they will have a positive serum anti-HAV IgG. A positive anti-HAV IgG lets the provider know the patient has lifetime immunity.
Complications from HAV
Acute liver injury by HAV can lead to fulminant hepatic failure. This is a rare complication and mostly seen in patients older than age 50 or in those with pre-existing liver problems. Mortality rate from fulminant hepatic failure can be as high as 80%.1 Cholestatic hepatitis from HAV can last for longer than 3 months and cause serum bilirubin levels, alkaline phosphatase, liver function tests and lipids to become abnormally elevated. This usually resolves spontaneously.8 Relapsing hepatitis A can occur in up to 10% of patients, occurring 6 months AFTER the onset of the acute illness. These patients need to be watched for the possible development of acute liver failure.9 Autoimmune HAV is a rare complication leading to a prolonged illness and findings of hyperglobulinemia and circulating autoantibodies. These patients may require a liver biopsy to determine further treatment.10
Occasionally, an anti-HAV IgM can be a false positive. A false-positive result should be suspected if the patient is asymptomatic, has no known HAV exposure or any risk factors for HAV. For example, a high titer of rheumatoid factor, or other cross-reacting antibodies, can interfere with anti-HAV IgM testing, causing a false-positive result.11 The CDC does not recommend anti-HAV IgM testing as a screening tool for HAV in asymptomatic patients or those with nonacute liver abnormalities.12
Pre- and post-exposure immunization
Active immunization starts in children between 12-23 months of age as they receive 2 doses of the inactivated HAV vaccine at 0 and 6 months.1 It is highly recommended in all adults as pre-exposure immunization for those who have not been previously immunized, in MSM, illegal drug users, have blood-clotting disorders, have chronic liver disease or are immunocompromised.
Passive immunization is with immune globulin (IG) and is recommended for those who are unimmunized and will be traveling to an HAV endemic area within the next 2 weeks. This will provide immediate protection. They can additionally, unless contraindicated, receive the first dose of the HAV vaccine and get the second dose when they return from their travels. Pre-exposure dosing is 0.1 mL/kg if traveling for 1 month or 0.2ml/kg if traveling for 2 months. IG may be repeated if traveling for longer than 2 months.7
Post-exposure treatment of HAV can be with either active or passive immunization. To be of maximum benefit, immunization should be given within 2-weeks post-exposure. Those who have been exposed to HAV and are pregnant, may be allergic to the HAV vaccine, are under the age of 1 year, are immunocompromised and/or are adults over the age of 40, should be given immune globulin (IG). IG only gives temporary protection, so active immunization with the HAV vaccine may be eventually required.13,14 Post-exposure dosing of IG is 0.1 mL/kg.8 Patients between the ages of 1-40 years, who are not pregnant or have no contraindications, may receive the HAV vaccine as their post-exposure treatment. Administration of either the HAV vaccine or the IG may actually prevent or attenuate symptoms, even though it does not always prevent the infection.15
Implications for practice
Providers should educate their patients on ways to prevent HAV transmission. They also need to offer the correct pre- and post-exposure immunizations, report infections to public health, design a supportive treatment plan for the patient infected by HAV, as well as recognize complications that require more interventions to avoid liver failure.