Researchers find link between age, HBV resistance
By Stacy Hsu / Staff reporter
Age may be a factor in battling the hepatitis B virus (HBV), researchers from National Taiwan University’s College of Medicine said yesterday.
Why a majority of adults infected with the virus are able to fight off the virus, while most infected newborns and toddlers end up developing a chronic hepatitis B infection has long baffled doctors and scientists.
Graduate Institute of Clinical Medicine associate professor Wang Hurng-yi (王弘毅), one of the authors of the research, said nearly 95 percent of adult-acquired hepatitis B infections lead to spontaneous clearance, while more than 90 percent of infected newborns and about 30 percent of infected children aged between one and five years old are unable to fight off the virus and subsequently develop a chronic infection.
“These statistics suggest that a person’s immune clearance of hepatitis B — which has affected nearly 2 billion people worldwide — is heavily age-related. However, as the reason for this remains unknown, our research team has made it its mission to find an answer,” Wang told a press conference in Taipei.
As a baby’s postnatal gut microbiota is not established until a toddler is two or three years old, the researchers presumed that gut commensals might be mainly responsible for preparing the liver’s immune system to fight the hepatitis B virus.
To prove this hypothesis, the researchers injected the virus into mice that ranged from from six-to-12 weeks old. They discovered that adult mice were able to clear the hepatitis B virus within six weeks after the injection, while their young remained hepatitis B virus-positive even after 26 weeks.
“We laced the drinking water of mice aged between five weeks and 12 weeks old with an antibiotic to have them gut-sterilized, resulting in a noticeable reduction in the level of gut bacteria DNA in stools,” Wang said.
Although the amount of stool bacteria in mice given antibiotics returned to normal shortly after antibiotic treatment ended, they were unable to clear the hepatitis B virus after they matured, Wang said.
The researchers also found that mice with the toll-like 4 receptor (TLR4) mutation were able to fight off the hepatitis B virus regardless of their age, offering a potential new treatment for neonates infected with hepatitis B at birth.
Chen Ding-shinn (陳定信), a hepatitis specialist and former head of the university’s College of Medicine, said more than half of the hepatitis B carriers in Taiwan caught the virus from their infected mothers during delivery.
“The link discovered between TLR4 deficiency in mice and the ability to clear HBV could be a giant step forward in finding ways to break the cycle of mother-to-newborn infection,” Chen said.
The research was published in the online version of the US journal Proceedings of the National Academy of Sciences on Monday.