Pediatric Patient With Transplacental-Acquired HBV Infection

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Ask the Experts about Liver Disease

From Medscape Gastroenterology

http://www.medscape.com/viewarticle/521190?src=mp

Pediatric Patient With Transplacental-Acquired HBV Infection

Question

Would you recommend treating a pediatric patient with

transplacental-acquired hepatitis B (HBV) infection, with positive serology

and hepatitis B virus DNA (HBV DNA) titer but normal liver enzymes? If so,

at what age, and what is your recommended treatment approach and duration?

Response from F. Balistreri, MD

Dorothy M. M. Kersten Professor of Pediatrics, University of Cincinnati

College of Medicine, Cincinnati, Ohio; Medical Director, Liver

Transplantation Program, Cincinnati Children’s Hospital Medical Center,

Cincinnati, Ohio

The probability of chronic HBV infection is inversely proportional to the

age at acquisition; chronic infection develops in 90% of those infected as

newborns and in less than 10% of children infected after 6 years of age.[1]

Thus, the risk for chronic disease in this patient is high. Infection in

early life leads to an " immune-tolerant " phase, characterized by

persistently high HBV DNA levels and the presence of hepatitis B e antigen

(HBeAg) in serum, which indicates ongoing viral replication. Tolerance to

the virus prevents immune-mediated damage to the infected liver cells,

preventing their elimination. Thus, alanine aminotransferase (ALT) levels

are usually normal during this phase and there is minimal histologic

evidence of liver disease.[2] The rate of spontaneous seroconversion is low

(less than 2% per year in children younger than 3 years of age); this

contrasts with seroconversion rates of 70% to 80% in children infected after

the perinatal period.[3,4]

The mild inflammatory response to HBV, suggested by normal ALT levels and

mild histologic changes, does not necessarily indicate that all is well.

Immune tolerance favors viral replication and cellular integration of HBV,

which is a potential precursor of hepatocarcinogenesis. Thus, chronic HBV

infection in perinatally infected patients is associated with a high risk of

developing cirrhosis and hepatocellular carcinoma (HCC).[5,6] This concern

is behind the efforts to develop an effective pharmacologic treatment for

chronic HBV infection in childhood: The goals are to halt viral replication

and prevent cirrhosis and HCC. The 2 medications approved in the United

States for children older than 2 years are interferon-alfa (administered

subcutaneously 3 times per week) and the nucleoside analogue lamivudine.

Each drug is associated with significant side effects. Most pediatric

hepatologists would suggest that interferon-alfa treatment should be offered

only to children with abnormal ALT levels and low HBV-DNA levels (ie,

evidence of immune activity).[7] Interferon-alfa-induced HBeAg clearance

rates of 20% to 40% have been noted in subjects with biochemical and/or

histologic evidence of active disease and low HBV-DNA levels.[8]

Interferon-alfa is less effective in patients who have acquired the

infection in infancy -- subjects such as this immune-tolerant patient who

has mild histologic changes, normal ALT levels, and high HBV-DNA levels.

Lamivudine-induced HBeAg clearance rates are similar to those achieved with

interferon-alfa; HBV-DNA level will decease, but may rebound with cessation

of therapy.[9] The advantage here is that oral forms, both tablet and

liquid, are available.

A future strategy may be to combine the immune-stimulating effect of

interferon-alfa (perhaps the weekly administered pegylated form) with the

antiviral action of lamivudine in " immunotolerant " children. Bottom line:

For patients such as the one presented here (in the absence of enrollment in

a treatment trial), I would attempt to treat with lamivudine after 2 years

of age, with careful monitoring for response and side effects.

Posted 01/25/2006

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References

Chang MH, Sung JL, Lee CY, et al. Factors affecting clearance of hepatitis B

e antigen in hepatitis B surface antigen carrier children. J Pediatr.

1989;115:385-390. Abstract

Lok ASF, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B

surface antigen-positive Chinese children. Hepatology. 1988;8:1130-1133.

Abstract

Hsu H, Chang M, Chen D, et al. Baseline seroepidemiology of hepatitis B

virus infection in children in Taipei, 1984: a study just before mass

hepatitis B vaccination program in Taiwan. J Med Virol. 1986; 18:301-307.

Abstract

Bortolotti F, Cadrobbi P, Crivellaro C, et al. Long-term outcome of chronic

type B hepatitis in patients who acquire hepatitis B virus infection in

childhood. Gastroenterology. 1990;99:805-810. Abstract

Bortolotti F, Calzia R, Cadrobbi P, et al. Liver cirrhosis associated with

chronic hepatitis B virus infection in childhood. J Pediatr.

1986;108:224-227. Abstract

Chen CH, Chen YY, Chen GH, et al. Hepatitis B virus transmission and

hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with

hepatocellular carcinoma. J Hepatol. 2004; 40:653-659. Abstract

Jara P, Bortolotti F. Interferon-alpha treatment of chronic hepatitis B in

childhood: a consensus advice based on experience in European children. J

Pediatr Gastroenterol Nutr. 1999;29:163-170. Abstract

Sokal EM, Conjeevaram HS, EA, et al. Interferon alfa therapy for

chronic hepatitis B in children: a multinational randomized controlled

trial. Gastroenterology. 1998;114:988-995. Abstract

Jonas MM, DA, Mizerski J, et al. Clinical trial of lamivudine in

children with chronic hepatitis B. N Engl J Med. 2002;346:1706-1713.

Abstract

Disclosure: F. Balistreri, MD, has disclosed no relevant financial

relationships.

Medscape Gastroenterology. 2006;8(1) ©2006 Medscape

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