Hepatitis B Foundation Issues Guidelines for Pediatric Screening, Monitoring, and Referral
By Laurie Barclay, MD
Medscape Medical News
October 12, 2009 — The Hepatitis B Foundation has issued guidelines for the screening, monitoring, initial management, and referral of children with chronic hepatitis B virus (HBV) infection. The new recommendations, which target clinicians, are published online in the October 5 issue of Pediatrics.
"The majority of children with chronic...HBV infection have no signs or symptoms of chronic disease, [so] identification requires a heightened awareness on the part of physicians," write Barbara A. Haber, MD, from Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, and colleagues. "It is important for practitioners to understand and use appropriate surveillance, monitoring, and timely referral. Our understanding of hepatitis B disease and the armamentarium of available therapies has grown substantially in recent years, calling for a fresh look at clinical practices and approaches."
Chronic HBV infection is defined as having persistently positive hepatitis B surface antigen (HBsAg) for longer than 6 months. Although most children with chronic HBV infection are asymptomatic and usually do not require treatment, they are at greater risk for advanced liver disease, liver cancer, and other severe complications later in life, sometimes even before age 30 years. The highest risk for hepatocellular carcinoma (HCC) occurs with HBV infection acquired via maternal-fetal transmission.
In the pediatric age group, the prevalence of HCC is low, but the morbidity and mortality of this outcome warrant vigilance among practitioners caring for at-risk children. It is crucial that these children have lifelong monitoring for progression of disease.
Once HBV infection is diagnosed in a child, subsequent management is not well defined. In North America, relatively few pediatric liver specialists concentrate on hepatitis B, and there have been no previous management guidelines specific for pediatric hepatitis B.
On November 11, 2008, the Hepatitis B Foundation, which is a nonprofit organization supporting research and promoting disease advocacy, assembled an expert panel of pediatric liver specialists nationally recognized in North America. Based on their expertise and on available evidence, their mandate was to develop and recommend strategies for screening, monitoring, initial management, and referral of children (< age 18 years) with chronic HBV infection.
Specifically, these guidelines were intended to help practitioners determine what additional tests to perform, how often to monitor based on test results, and when to refer to a pediatric liver specialist. Fostering a partnership between the practitioner and liver specialist should facilitate treatment of children with this lifelong infection.
Children who should be screened for chronic HBV infection include the following:
Children born in a country endemic for HBV, even if they received hepatitis B vaccine in their country of origin. Endemic regions are Asia, Africa, South- and mid-Pacific Islands, Eastern and Mediterranean Europe, Greenland, Russia, the Middle East, Amazon Basin, and Caribbean.
Indigenous populations from the Arctic, Australia, and New Zealand.
Children born in the United States to immigrant parents from endemic areas.
Infants born to HBsAg-positive mothers.
Children in the same household as someone who is HBsAg positive, including those children who received hepatitis B vaccine after birth who were not screened before vaccination.
Specific recommendations for monitoring children who have chronic HBV infection include the following:
Referral to a pediatric liver specialist is indicated for any child who has an elevated alanine aminotransferase (ALT) or alpha-fetoprotein level, who has a positive family history of HCC, or who is HBeAg negative but has an HBV DNA level of more than 2000 IU/mL.
The baseline evaluation should include a hepatic function panel with ALT level and complete blood count including white blood cell/platelet counts.
Definition of elevated ALT level is a level greater than the testing laboratory upper limits of normal or more than 40 IU/L, whichever is lower.
ALT and alpha-fetoprotein levels should be measured every 6 to 12 months.
HBeAg/Anti-HBe and HBV DNA levels should be measured every 12 months.
Especially for children with a family history positive for HCC or in whom ALT or alpha-fetoprotein level is elevated, ultrasound every 1 to 2 years may be indicated, according to many pediatric specialists.
Treatment of HBV infection in children is complicated by potential development of drug resistance and other risks. Antiviral drugs that are currently approved by the US Food and Drug Administration for use as initial therapy for chronic hepatitis B in children are adefovir for ages 12 years and older, entecavir for ages 16 years and older, interferon alfa-2b for children 12 months and older, and lamivudine for children 3 years and older.
"For children who are HBeAg-positive with elevated ALT levels and compensated liver disease, an observation period of 6 to 12 months should be considered to determine if spontaneous HBeAg seroconversion occurs," the guidelines authors conclude. "There are many unanswered questions that play into the decision to initiate treatment with antiviral therapy, not least of which are the potential efficacy, duration of therapy, and risk of drug resistance in view of the limited therapeutic options for children. Again, a successful partnership between the primary practitioner and pediatric liver specialist can enhance the success of screening, initial management, and monitoring of children with this lifelong infection."
The workshop leading to development of these guidelines was convened and funded by the Hepatitis B Foundation, which is supported primarily by federal, state, and private foundation grants and individual charitable donations, with small unrestricted educational grants from Bristol-Myers Squibb, Gilead Sciences, Idenix, Merck, and Novartis.
Some of the guidelines authors have disclosed various financial arrangements with Bristol-Myers Squibb, Gilead, Roche, Novartis, and/or Merck.
