Pediatric Hepatitis B Treatment & Management

From the time of initial diagnosis, optimal management of hepatitis B virus (HBV) infection requires a lifetime of routine monitoring, even when patients are asymptomatic. The aims of treatment of chronic hepatitis B are to achieve sustained suppression of HBV replication and remission of liver disease. The ultimate goal is to prevent cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Children with HBV infection may not need treatment until well into their adolescent years or adulthood.

To date, no conclusive evidence from randomized controlled trials of anti-HBV therapy has demonstrated a beneficial impact on any of these primary clinical outcomes because cirrhosis, hepatocellular carcinoma, and death often do not occur for many years after infection with HBV and would therefore require long-term evaluation of therapy to demonstrate benefit. As a consequence, most published reports of anti-HBV therapy use changes in short-term virologic, biochemical, and histologic parameters to infer the likelihood of long-term benefit. Parameters used to assess treatment response include normalization of serum ALT, decrease in serum HBV DNA level, loss of HBeAg with or without detection of anti-HBe, and improvement in liver histology.

Currently, 7 agents have been approved by the US Food and Drug Administration (FDA) for use in the treatment of adults with chronic hepatitis B in the United States. These agents, categorized as either interferons (IFN-a2b and peginterferon-a2a) or nucleoside or nucleotide analogues (lamivudine, adefovir, entecavir, tenofovir, telbivudine), may be used as monotherapy or in combination. Interferon use has a defined, self-limited course; in contrast, therapy with nucleoside or nucleotide analogues can be long-term, often indefinite treatment.

Lamivudine is now considered first-line therapy, eclipsing interferon. Consider lamivudine in patients who fail or are unlikely to respond to interferon therapy or patients who cannot tolerate interferon.

Discontinue lamivudine only when repeated assays demonstrate HBeAg loss or seroconversion to HBeAb; the time for stopping treatment, however, is controversial. Results of a histologic study reported that lamivudine treatment for 3 y reduced necroinflammatory activity and reversed fibrosis (including cirrhosis) in most patients.

Surgical care for HBV infection includes liver transplantation for decompensated liver disease and surgical resection of hepatocellular carcinoma.

The American Association for the Study of Liver Diseases (AASLD) has published guidelines on the management of chronic hepatitis B.^[6] The proceedings of the NIH 2008 Consensus Conference on Management of Chronic Hepatitis B were considered in the development of these guidelines.^[7]

See also Pediatric Hepatitis A, Pediatric Hepatitis C, and Viral Hepatitis.

Indications for hospital admission

Most patients do not require hospital care, but patients with clinically severe illness may require hospitalization.

A prolonged prothrombin time, low serum albumin level, hypoglycemia, and very high serum bilirubin values suggest severe hepatocellular disease; patients with these findings require prompt hospital admission.

Consultations

Consultations may include the following:

• Infectious disease specialists for placement in therapeutic protocols
• Gastroenterologist for biopsy assessment and therapy

A high-energy diet is desirable, and because many patients may have nausea late in the day, they best tolerate their major caloric intake in the morning. Intravenous feeding is necessary in the acute stage if the patient has persistent vomiting and cannot eat. Although forced and prolonged bed rest is not essential for full recovery from acute hepatitis, many patients feel better with restricted physical activity.

Hepatitis B is one of the major diseases that can be prevented with vaccination. Two types of recombinant hepatitis B vaccines are licensed for use in the United States; both are effective and safe.

Universal vaccination refers to the administration of HBV vaccine to all infants as a part of the routine childhood immunization schedule and to all children younger than 11 or 12 years who have not previously received a vaccine. Rapid (0-, 1-, and 2-mo) and standard (0-, 1- to 2-, 6-mo) schedules have identical efficacy.

Passive immunization refers to the administration of preformed human or animal antibody, in the form of hepatitis B immunoglobulin (HBIG), to patients after or just before exposure. The current recommendation for neonates of mothers who are HBV surface antigen (HBsAg) positive is to administer HBIG 0.5 mL intramuscularly with the first dose of recombinant HBV vaccine within 12 hours of birth.

After immunization of exposed infants, serology should be tested for HBsAg and anti-HBs at age 9-18 months. An HBsAg-positive finding in an exposed infant, which is rare, indicates failure of immunoprophylaxis, and the third vaccine dose is not necessary. Breastfeeding is acceptable and does not pose a risk of transmitting HBV to infants who have begun prophylaxis.^[8]

For preterm infants who weigh less than 2000 g and are born to mothers with unknown HBsAg status, 0.5 mL HBIG should be given within 12 hours. The birth dose of vaccine should not be counted, and 3 additional doses are given according to recommendations. In infants of infected mothers, combined treatment with the vaccine and HBIG has 79-98% efficacy in preventing chronic HBV infection.

Patients on dialysis and those who are immunocompromised need to be evaluated annually for hepatitis B; if the anti HBsAb level is less than 10 mIU/mL, a booster dose is recommended.

Testing of hepatitis serology for immune response is recommended for high-risk groups such as homosexuals and bisexuals, patients on dialysis, sexual and household contacts of hepatitis B carriers and patients with human immunodeficiency virus (HIV) infection.

After 3 primary doses of the vaccine, if no serologic response with anti-HBs of 10 mIU/mL is noted, reimmunization with a 3-dose series is recommended. If the response if still negative, the patient is unlikely to mount antibody with additional doses. Some experts recommended the second course be with the high-dose version of the vaccine typically used for dialysis patients.

Twinrix is a combination of hepatitis B (Engerix-B, 20 mcg) and hepatitis A (Havrix, 720 ELU) vaccine approved for people aged 18 years or older in a 3-dose schedule administered at 0 months, 1 month, and 6 or more months later.

Some combination vaccines used in the routine vaccination schedule result in infants receiving 4 doses of HBV vaccine (eg, at 0, 2, 4, and 6 mo). This is considered acceptable.

All persons with chronic hepatitis B who are not immune to hepatitis A should receive 2 doses of hepatitis A vaccine 6-18 months apart. Infants of HBsAg-positive women should receive hepatitis B immunoglobulin and hepatitis B vaccination within 12 hours of birth, a complete set of 3 vaccinations, and long-term follow-up.

Reserve routine screening using ultrasonography and alpha-fetoprotein determination for patients with severe chronic active hepatitis, cirrhosis, or both.^[9]