Abstract
Hepatitis B virus (HBV) infection is a challenging public health problem in China and worldwide. Mother-to-child transmission is one of the main transmission routes of HBV in highly endemic regions. However, the mechanisms of HBV perinatal transmission in children have not been clearly defined. The aim of this study was to demonstrate the association between single-nucleotide polymorphisms (SNPs) in IFN-γ signaling pathway and HBV infection or breakthrough infection in children. Two hundred and seventy-four HBV-infected children defined as test positive for hepatitis B surface antigen (HBsAg) and 353 controls defined as negative for HBsAg in China were recruited from October 2013 to May 2015. SNPs in IFN-γ signaling pathway including IFNG, IFNGR1, IFNGR2, and IL12B were genotyped. Rs2234711 in IFNGR1 was significantly associated with HBV infection in children (OR = 0.641, 95% CI: 0.450–0.913). In addition, rs2234711 was also significantly associated with HBV breakthrough infection in children born to HBsAg-positive mothers (OR = 0.452, 95% CI: 0.205–0.998). Our study confirmed that genetic variants in IFN-γ signaling pathway have significant associations with HBV infection, especially with HBV breakthrough in children. This study provides insight into HBV infection in children and could be used to help design effective strategies for reducing immunoprophylaxis failure.
Highlights
Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease, accounting for high morbidity and mortality of liver-associated disease worldwide [1]
A total of 172 children born to hepatitis B surface antigen (HBsAg)-positive mothers had been administrated with hepatitis B immunoglobulin (HBIG) within 24 h after birth and HB vaccine according to the program in our study
We further studied the association between the 5 single-nucleotide polymorphisms (SNPs) and HBV breakthrough infection in children who were born to HBsAg-positive mothers and had been vaccinated with HBIG and HB vaccine according to the standard procedure
Summary
Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease, accounting for high morbidity and mortality of liver-associated disease worldwide [1]. Approximately 2 billion people have serological evidence of HBV infection, leading to development of chronic infection in an estimated 257 million people and 887000 deaths in 2015 [2]. E initial age of HBV exposure is strongly associated with the possibility of developing chronic HBV infection (CHB). When infants are infected with HBV within 1 year after birth, 80–90% of them develop persistent infection. Before 6 years of age, 30–50% of infected children develop chronic HBV infection. For older children and adults infected with HBV, a lower rate (5–10%) of chronicity is observed [3]. A quarter of patients with CHB will progressively develop cirrhosis, liver failure, and/or hepatocellular carcinoma [4]
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