Infantile Hepatitis B in Immunized Children: Risk for Fulminant Hepatitis and Long-Term Outcomes

Abstract

BackgroundInfantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B.MethodsThe clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median = 4.4 years, range 0.6–18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed.ResultsAmong the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age <7 months) and negative maternal hepatitis B e antigen (HBeAg) were associated with FH (p = 0.03 and p = 0.01, respectively). An infantile fulminant hepatitis B risk score using maternal/infant HBeAg positivity and onset age was proposed. Among the FH cases, the rate of mortality, HBsAg clearance, and chronic HBV infection were 47.6%, 38.1%, and 14.3%, respectively. Among the NFH cases, 35% developed chronic infection. Of the 9 chronically infected children received long-term follow-up, 8 had HBeAg seroconversion before 4 years of age. One case of FH developed hepatocellular carcinoma 14 years later.ConclusionsMaternal HBsAg + /HBeAg- and early onset age were risk factors for FH in immunized infants. A significant portion of patients with FH or NFH evolve to chronic HBV infection, with HBeAg seroconversion in young childhood. Close surveillance for hepatocellular carcinoma is warranted in patients surviving infantile hepatitis B.

Hepatitis B virus infection in children and adolescents

“…Age of acquisition is the key determinant of chronic infection, which occurs in 90% of infected neonates and infants but in <5% when infection is acquired in adulthood. [29][30][31][32][33] Infections are usually asymptomatic and anicteric in vertically infected children, 10,34 but acute infection may be associated with severe symptoms and fulminant hepatitis in both adults, 35 and children. 36 Chronic infection may lead to progressive liver disease and development of complications such as cirrhosis and HCC mainly in adulthood 37 and extrahepatic manifestations that can also present in infancy and early childhood.…”

Fulminant hepatitis B virus (HBV) infection in an infant following mother-to-child transmission of an e-minus HBV mutant: Time to relook at HBV prophylaxis in South African infants

“…[11] Though less common, HBeAg-negative women can also transmit HBV infection and this can have severe consequences for their infants. [12] The current HBV prophylaxis in SA falls woefully short of current international recommendations, namely that all infants should receive a birth dose of HBV vaccine (as recommended by the World Health Organization [13] ), pregnant women should be screened for hepatitis B surface antigen (HBsAg), and HBV VL should be performed on positive patients. Lastly, mothers with HBV VLs >200 000 IU/mL (American Association for the Study of the Liver and European Association for the Study of the Liver) or >6 log IU/mL (Asian Pacific Association for the Study of the Liver) should receive antiviral prophylaxis with lamivudine, telbivudine or tenofovir in the second and third trimesters of pregnancy.…”

“…In a study of infants infected with HBV through MTCT, HBeAg-negative status in mothers was more likely to be associated with fulminant hepatitis in their infants, while infants of HBeAg-positive mothers were more likely to have mild hepatitis followed by chronic infection. [12] When did transmission happen?…”

Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers

“…In concordance with prenatal screening strategies, most guidelines suggest post‐vaccination serological testing to assess an infant's immune response at age 6‐12 months or at 1‐2 months after the final vaccine dose . However, fulminant hepatitis, a rare but devastating complication of HBV infection or clinically obscure hepatitis, may occur in infancy before 6 months . In addition, indications for anti‐viral treatment may extend to infancy in the future perspective.…”

“…17 However, fulminant hepatitis, a rare but devastating complication of HBV infection or clinically obscure hepatitis, may occur in infancy before 6 months. 18 In addition, indications for anti-viral treatment may extend to infancy in the future perspective. Post-vaccination serologic testing in early infancy before 6 months may identify the at-risk infants that require clinical monitoring or intervention.…”