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Viral hepatitis presentations in pediatrics
Inflammation of the liver occurs due to a variety of causes, both infectious — viruses, bacteria, parasites and fungi — and noninfectious — toxins, metabolic, systemic illness and autoimmune.
When considering hepatitis, it is reasonable to start with an appreciation of how we test your liver: function, cellular integrity and biliary system. The liver function tests include albumen, clotting factors and bilirubin; tests of cellular damage include measure of serum transaminases. Remember that these are not specific for liver. Biliary function is tested using gamma-glutamyl transpeptidase (GGTP), bilirubin and alkaline phosphatase.
Margaret C. Fisher
With these basic facts in mind, the remainder of this article will deal with hepatitis caused by hepatitis viruses: A, B, C, D and E.
Hepatitis A
Hepatitis A virus is an RNA virus of the Picornaviridae family. It is transmitted by the fecal–oral route, either directly between people or by contamination of food. There were about 17,000 reported cases of hepatitis A virus infection in 2010; note that this is likely to be a gross under-estimation because many children with hepatitis A infection are completely asymptomatic.
Risks for infection include contact with a person who has hepatitis A infection, travel to an area where the disease is endemic, having a child who attends a child care center, having adopted a child internationally, being a man who has sex with men, using illicit drugs and having eaten contaminated foods. The incubation period from ingestion to illness is 15 to 50 days with an average of 28 days.
Illness due to hepatitis A virus varies from none to typical hepatitis. Children younger than 6 years are often asymptomatic or have mild illness, whereas 40% to 50% of children aged 6 to 14 years develop jaundice; 70% to 80% of those older than 14 years develop jaundice. Other symptoms include malaise, anorexia, nausea and fever. The illness is usually self-limited and symptoms typically resolve within 2 weeks. About 10% of symptomatic patients will have a prolonged and relapsing illness that can last for 6 months.
Fulminant hepatitis is rare. Hepatitis A virus infection is diagnosed with a combination of clinical findings and consistent serology. Tests measuring antibody against the virus are positive for total immunoglobulin and for IgM antibody. The treatment is supportive.
This infection is preventable by immunization; universal immunization is recommended for all children in the United States who are aged 1 to 2 years. These children should receive two doses of the vaccine 6 months apart. Catch-up immunization for older children and adults is very reasonable. This is recommended for families considering international adoption and for at-risk groups. Post-exposure immunization or receipt of immune globulin is effective in preventing illness.
Hepatitis B
Hepatitis B virus is a DNA virus of the Hepadnaviridae family. The virus is transmitted by blood and body fluids. It is estimated that there are 38,000 new cases of hepatitis B per year in the United States; there are about 1.2 million people living with chronic infection. Person-to-person transmission and vertical transmission are the routes of infection. The risk for vertical transmission from a mother with hepatitis B infection is 70% to 90% if the mother is hepatitis B e antigen-positive (HBeAg+) and 5% to 20% if the mother is HBeAg-negative. The incubation period is from 45 to 160 days with an average of 90 days. Terminology regarding HBV is shown in Figure 1. These terms are used in diagnosis and prognosis.
Symptomatic illness due to infection with HBV varies depending on the age of the person who has been infected: less than 1% of children younger than 1 year will have symptoms, whereas 5% to 10% of those aged 1 to 5 years are symptomatic, and 30% to 50% of those older than 5 years will have symptoms.
Symptoms range from nonspecific complaints, to hepatitis, to fulminant liver failure. Extrahepatic signs and symptoms include arthralgia, rashes, polyarteritis and glomerulonephritis; these may precede the onset of hepatitis.
Diagnosis is established by clinical findings and serology. In acute infection, the patient will have circulating hepatitis B surface antigen (HBsAg) and IgM antibodies to hepatitis B core antigen (IgM anti-HBc). Chronic infection is defined as 6 months of viral infection.
The CDC has established this laboratory definition of chronic infection: either IgM anti-HBc–negative AND a positive result on one of the following tests: HBsAg, HBeAg or nucleic acid test for HBV DNA (including qualitative, quantitative and genotype testing), or HBsAg+ or nucleic acid test for HBV DNA-positive (including qualitative, quantitative and genotype testing) or HBeAg+ two times at least 6 months apart. In addition, any combination of these tests performed 6 months apart is acceptable.
The risk for chronic infection is age-related: more than 90% of children younger than 1 year will be chronically infected, 25% to 50% of those aged 1 to 5 years and 5% to 10% of those older than 5 years at the time of infection. Chronic infection can be asymptomatic but may lead to cirrhosis, liver failure and hepatocellular carcinoma. The risk for cancer depends on the duration of infection, the amount of liver damage from the virus or other causes, the levels of HBV and the presence of coinfection.
It is estimated that there are 3,000 deaths per year in the United States due to HBV infection. Treatment of the acute infection is supportive. Patients with chronic infection should receive hepatitis A vaccine if not previously immunized and should be screened periodically with liver enzymes, alpha-fetoprotein concentrations and ultrasounds; it is appropriate to refer such patients to a specialist in hepatology. A variety of drugs may be useful for patients with chronic infection; these include nucleosides, nucleotide analogues and interferons, which are approved for use in adults. Some are approved for children.
HBV infection is preventable. Universal immunization is recommended at the time of birth, ideally within the first 12 hours of life, and universal immunization is recommended for all adolescents. Health care workers (HCWs) and all those with potential exposure to blood or body fluids should be immunized. High-risk adults and anyone who wants to decrease their risk should be immunized.
Post-exposure immunization is effective; hepatitis B immune globulin (HBIG) plus hepatitis B vaccine is recommended. Prevention of perinatal transmission of the virus is a public health mandate because these infants become chronic carriers.
Prevention is accomplished by screening all pregnant women for HBsAg to identify carriers. HBIG and hepatitis B vaccine is given to the newborn of a carrier mother. If the child is born prematurely and weighs less than 2,000 g, an extra dose of hepatitis B vaccine is given to ensure protection. Babies born to carrier mothers should be screened at age 9 to 18 months for HBsAg and antibody (anti-HBsAg).
For HCWs who are exposed to HBsAg+ blood, the following actions should be taken. First, all workers should be educated regarding decreasing the risk for needle stick and blood exposures. If the worker is known to be immune (anti-HBsAg level >10 mIU/mL), no additional measures are needed. Second, if the worker is a known nonresponder or was not immunized, then HBIG is given and the vaccine series is started for the unimmunized person. Third, if the worker was immunized, but not previously tested for antibody, then the person is tested and HBIG is provided if the antibody level is not protective.
In 2014, there is a new dilemma because many adolescents and young adults who were previously immunized are entering health care professions or other professions where they may be exposed to blood or body fluids. Antibody levels are required by many professional schools or by hospitals and first responder groups. On occasion, the previously immunized person has no detectable antibody or antibody levels below the protective level (10 mIU/mL). In this case, repeat immunization is recommended. In my opinion, it is reasonable to give a single dose of the vaccine and repeat the antibody level after 3 to 4 weeks. If antibody is detected, this person is a responder and no additional vaccine is required. If the titer remains negative, the full series should be given and the titer repeated. If positive, the person is considered a responder, and if negative, a non-responder. Please note that this is my personal opinion and there are no official recommendations.
Hepatitis C
Hepatitis C virus is an RNA virus of the Flaviviridae family. Infection is transmitted by blood. There are an estimated 17,000 new cases each year and about 3.2 million people living with chronic infection in the United States. These viruses are probably not transmitted sexually. Perinatal transmission occurs in 5% to 6% of infants born to infected mothers. The incubation period is 14 to 180 days with an average of 42 to 49 days.
Most infections with HCV are asymptomatic. When present, symptoms tend to be mild and insidious in onset. Unfortunately, persistent infection occurs in 80% of patients. Chronic hepatitis occurs in 80% of infected adults but seems to be less common in children. Diagnosis depends on detection of antibody to HCV and detection of HCV RNA. It is appropriate to refer patients with HCV infection to a specialist in hepatology.
Monitoring for evidence of liver damage and development of liver cancer are important. There are now many studies and many agents available for antiviral therapy; some are approved for use in children. There are ongoing trials to determine the optimal therapy. Current therapies involve interferons combined with ribavirin. Response varies depending on the genotype of the infecting strain. There are no vaccines against HCV. Routine screening of all people born between 1945 and 1965 has been recommended by the CDC.
With regard to pregnancy, screening is not recommended. The risk for vertical transmission is about 5%. Infants born to mothers known to be positive for HCV should be screened after age 18 months for the presence of antibody. Earlier diagnosis of infection can be made using HCV RNA testing, which can be performed in children as young as age 1 month. If infected, these children should be referred to a specialist in hepatology.
Hepatitis D
Hepatitis D virus is an RNA virus that cannot cause infection alone; rather it can only infect people already infected by HBV. The infection occurs either simultaneously with HBV or as a superinfection in people with chronic HBV infection. Coinfection leads to a more severe illness with increased risk for fulminant hepatitis. Diagnosis is made by detection of antibody to hepatitis D and/or detection of hepatitis D viral RNA. Prevention of this infection depends on prevention of HBV infection.
Hepatitis E
Hepatitis E virus is an RNA virus of the Hepeviridae family. The virus is acquired by fecal–oral transmission, usually due to contaminated water. Genotypes 3 and 4 infect pigs and can be acquired by people who eat undercooked pork. Hepatitis E viral infection occurs worldwide in sporadic outbreaks, and Africa and Asia report the highest rates of infection. Although disease is uncommonly diagnosed in the United States, serologic studies have reported that about 20% of US adults have antibody against hepatitis E virus.
Illness is more common in adults and more severe in pregnant women. Vertical transmission can result in fetal loss or infection of the newborn and infant mortality. There are no approved serologic tests in the United States. Treatment is supportive.
To conclude, I have a few take-home points.
Hepatitis A: Catch-up immunizations should be considered in adolescents, and vaccine is effective as post-exposure prophylaxis.
Hepatitis B: Prevent perinatal infections by routinely vaccinating babies within 12 hours of birth. Be ready to deal with adolescents who test negative for hepatitis B antibody.
Hepatitis C: Vertical transmission occurs, so screen babies at age 18 months if they were born to mothers with hepatitis C infection.
Hepatitis D: This virus depends on hepatitis B, so universal hepatitis B vaccination should eliminate the infection.
Hepatitis E: The virus is endemic in Africa and Asia but likely occurs in the United States. Stay tuned for more information about this virus.
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Disclosure: Fisher reports no relevant financial disclosures.