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Am Fam Physician. 2021;104(4):368-374

Patient information: A handout on this topic is available at https://familydoctor.org/condition/hepatitis-a.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. The incidence of infection in the United States decreased by more than 90% after an effective vaccine was introduced, but the number of cases has been increasing because of large community outbreaks in unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice and are more common in older children and adults. People are most infectious 14 days before and seven days after the development of jaundice. Diagnosis of acute infection requires the use of serologic testing for immunoglobulin M anti–hepatitis A antibodies. The disease is usually self-limited, supportive care is often sufficient for treatment, and chronic infection or chronic liver disease does not occur. Routine hepatitis A immunization is recommended in children 12 to 23 months of age. Immunization is also recommended for individuals at high risk of contracting the infection, such as persons who use illegal drugs, those who travel to areas endemic for hepatitis A, incarcerated populations, and persons at high risk of complications from hepatitis A, such as those with chronic liver disease or HIV infection. The vaccine is usually recommended for pre- and postexposure prophylaxis, but immune globulin can be used in patients who are too young to be vaccinated or if the vaccine is contraindicated.

Hepatitis A is a common cause of acute hepatic inflammation and jaundice worldwide, and until 2004 it was the most commonly reported type of hepatitis in the United States.1 A combination of widespread vaccination, food safety practices, and improved sanitation decreased the incidence of hepatitis A in the United States from the 1970s until 2015. However, infection rates have recently increased because of large community outbreaks in susceptible individuals.2

Clinical recommendation Evidence rating Comments
Serologic testing for immunoglobulin M anti–hepatitis A antibodies should be performed to confirm suspected hepatitis A.2,4 C Consensus-based national guidelines from ACIP and the Centers for Disease Control and Prevention
Symptoms may be nonspecific
Hepatitis A vaccination should be offered to children 12 to 23 months of age and other populations at increased risk.2 C Consensus guidelines from ACIP
Confers lifelong immunity
Pre-exposure prophylaxis is indicated for unimmunized patients planning to travel to an area with increased incidence of hepatitis A (everywhere outside of the United States except for Australia, Canada, Japan, New Zealand, and western Europe).2 C Consensus guidelines from ACIP
Children younger than six months and persons with a contraindication to hepatitis A vaccine should receive immune globulin (Gamastan).
Persons older than 40 years and those with chronic liver disease should receive both hepatitis A vaccine and immune globulin.
All others should receive hepatitis A vaccine only.
Postexposure prophylaxis is recommended for all unvaccinated individuals who have had significant exposure to people with hepatitis A in the preceding two weeks.2 C Consensus guidelines from ACIP
Children younger than 12 months and people with a contraindication to hepatitis A vaccine should receive immune globulin.
Persons older than 40 years and those with chronic liver disease should receive both hepatitis A vaccine and immune globulin.
All others should receive hepatitis A vaccine only.

Epidemiology

Worldwide, an estimated 1.4 million cases of hepatitis A are reported each year, and it remains a major infectious disease for most of the world's population.3 Before the development and implementation of the hepatitis A vaccine, annual cases of acute infection in the United States were reported in the tens of thousands, peaking at 59,606 cases in 1971.4 Following the licensing of the first vaccine, the annual number of U.S. cases fell by 92% between 1995 and 2010.1 This decline in cases occurred after only moderate vaccination coverage was achieved, indicating a substantial herd immunity effect.5 However, the United States has seen a steep increase in cases, driven by several person-to-person and food-related outbreaks beginning in 2016.4,6,7 These episodes, along with several outbreaks in Europe over the past five years, have led to resurgences of hepatitis A in areas considered low-endemic regions.3,8 The lack of widespread adult immunity in the affected nations, whether due to poor immunization rates or few previous infections, provides fuel for outbreaks.9 Advances in virus genotyping have allowed researchers to track outbreak origin and trajectory.10

Transmission and Risk Factors

Hepatitis A virus is a nonenveloped positive-strand RNA virus classified as a picornavirus, whose only natural host is humans.1 Remarkably stable in many environments and able to survive on surfaces for weeks, hepatitis A virus is transmitted through ingestion of infected stool particles.1113 The virus is absorbed in the stomach and intestines, travels to the liver via the portal circulation, and replicates in hepatocytes.11,12 Detectable virus appears in blood and feces approximately 10 to 12 days after infection and may be excreted in stool for up to three weeks after the onset of symptoms.1,12 Viral shedding may begin weeks before symptom onset, contributing to the scope of outbreaks.4,12 Close interpersonal or sexual contact with an infected person and consumption of contaminated food or water are the most common routes of infection.4,14 Less commonly, infection has resulted from injection drug use or blood transfusion.4,12,14 Risk factors for contracting hepatitis A and characteristics that increase the risk of complications from infection are listed in Table 1.2

People at higher risk of hepatitis A
Illegal drug users
International travelers to areas with high or intermediate rates of endemic infection (all areas outside of the United States except Australia, Canada, Japan, New Zealand, and western Europe)
Men who have sex with men
People who are homeless
People living in group settings for those with developmental disabilities
People who are incarcerated
People who have personal contact with an international adoptee from a country with high or intermediate rates of endemic infection
People with occupational risk for exposure (e.g., individuals working with hepatitis A virus in laboratories)
People at higher risk of severe disease from hepatitis A
People with chronic liver disease
 Alcoholic liver disease
 Autoimmune hepatitis
 Cirrhosis (any type)
 Fatty liver disease
 Hepatitis B
 Hepatitis C
 Transaminase levels more than two times the upper limit of normal
People with HIV infection

Presentation and Complications

An incubation phase of approximately 30 days (range = 15 to 50) is followed by the development of infectious symptoms in most adults and children six years and older.4,12 Approximately 70% of children younger than six years remain asymptomatic.4 Patients often initially experience nonspecific flulike symptoms of fever, malaise, nausea with vomiting, and abdominal pain that may progress to the classic findings of dark urine and jaundice in 70% of adults and older children.4,12 Although less common, diarrhea, joint pain, pruritus, and skin eruptions may also occur.12 Hepatomegaly and jaundice are the most common examination findings, occurring in 78% and 40% to 80% of patients, respectively.12

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