- Category: HBV Vaccines
- Published on Tuesday, 04 September 2012 00:00
- Written by Liz Highleyman
An unexpectedly high proportion of gay/bisexual men and injection drug users develop chronic hepatitis B rather than clearing the infection, Amsterdam researchers reported in the September 2012 Journal of Hepatology. Other recent studies found that more than one-quarter of children born to mothers with hepatitis B showed evidence of "occult" HBV infection despite vaccination at birth, and that some individuals vaccinated as children may still show evidence of infection as adults.
HBV, a blood-borne virus, may be spread through shared drug injection or medical equipment, from mother-to-child during pregnancy or delivery, and through sexual transmission. Chronic hepatitis B remains a leading cause of liver cirrhosis and liver cancer worldwide, but widespread use of an effective vaccine has dramatically lowered the rate of new infections over the past 3 decades.
Gay Men and Injection Drug Users
Most people who become infected with HBV can clear the virus spontaneously, without treatment, and it is generally estimated that only about 5% to 10% will develop chronic infection. Among people infected as infants, the proportions are reversed, with most becoming chronically infected.
In a study described in the September 2012 Journal of Hepatology, Robin van Houdt from the Amsterdam Public Health Service and colleagues looked at rates of spontaneous viral clearance and chronic HBV infection among men who have sex with men (MSM) and injection drug users (IDUs), groups that tend to experience frequent HBV exposure. While being infected once confers immunity against reinfection, they speculated that repeated exposure might lead to a different rate of viral clearance compared with that of the general adult population.
The researchers retrospectively analyzed blood serum samples from 1862 MSM and 1268 IDUs participating in the Amsterdam Cohort Studies between 1984 and 2002. Samples were retrospectively tested for hepatitis B core antibodies (anti-HBc), hepatitis B surface antigen (HBsAg), and HBV DNA. As of 2003, all cohort participants were vaccinated, making further testing irrelevant.
- 147 study participants seroconverted, or became positive for anti-HBc -- indicating HBV infection -- during the follow-up period.
- The median age at the time of the acute HBV infection was 31 years.
- Among those with acute infection, 23% of MSM and 28% of IDUs developed chronic infection -- considerably higher than the adult general population rate of 5% to 10%.
- In both cohorts, being younger was an independent risk factor for developing chronic HBV infection (OR 0.9).
- Among IDUs, HIV/hepatitis C virus (HCV) coinfection was also associated with developing chronic HBV infection (OR 32.1).
"Compared with the general population, MSM and [IDUs] had an unanticipated high rate of developing chronic HBV infections," the study authors concluded.
"HIV/HCV coinfection proved to be an important risk factor for developing chronic HBV infections in [IDUs]," they continued. "The reason for the high rate of MSM becoming chronically infected remains unclear."
Infants Born to Mothers with HBV
In another study reported in the same issue, Sajad Shahmoradi from Tehran University of Medical Sciences in Iran and colleagues assessed the prevalence of occult HBV infection in a group of children who developed HBV infection despite immuno-prophylaxis after birth.
To prevent mother-to-child HBV transmission, babies born to women with hepatitis B should be given their first HBV vaccine dose plus injected hepatitis B antibodies (HBIG) within 12 hours after birth.
Occult or "hidden" HBV infection refers to detectable HBV DNA in blood or the liver in the absence of detectable HBsAg. Its clinical significance is unclear, but some studies suggest it raises the risk of cirrhosis and liver cancer.
The researchers tested blood serum from 75 HBsAg negative children born to HBsAg positive mothers; all received prophylactic vaccination and HBIG soon after birth. The investigators initially measured HBV DNA using real-time polymerase chain reaction (PCR); they also did further testing using a sensitive standard PCR with primers for all HBV genes and performed direct gene sequencing.
- Overall, 55 children (73%) tested positive for hepatitis B surface antibodies (anti-HBs), an expected outcome of vaccination.
- HBV DNA was detected in 21 of the 75 children (28%), at levels ranging from 77 to 9240 copies/mL.
- All children with detectable HBV DNA tested positive for hepatitis B surface antibodies.
- 5 children (24%) tested positive for hepatitis B core antibodies (indicating prior HBV exposure), but none were positive for only anti-HBc.
- 13 of the children (62%) with occult HBV had at least 1 mutation in viral gene regions known to be involved in immune recognition, including 10 with the G145R escape mutant; 8 samples (38%) did not show any mutations.
"HBV occult infection seems to be relatively frequent in immunized children born to HBsAg positive mothers," the researchers wrote. "HBsAg negativity is not sufficient to completely exclude HBV DNA presence."
"These findings emphasize the importance of considering occult HBV infection" in areas where HBV is not endemic in the population and has low-to-intermediate prevalence, they added.
Vaccine Escape Over Time
In the third study, described in the August 2012 issue of Gastroenterology, Ming-Wei Lai from the Chang Gung Memorial Hospital in Taoyuan, Taiwan and colleagues looked at HBV serology and genotypic characteristic over long periods after infant vaccination.
"Despite the success of a universal vaccination program against hepatitis B virus in Taiwan, a small but substantial proportion of individuals remain infected by mutant viruses that escape the vaccine," they noted as background.
The researchers measured HBsAg, hepatitis B core antibodies, and hepatitis B surface antibodies in 1214 serum samples collected throughout Taiwan from individuals age 6 months to 88 years. HBV DNA was detected using PCR and gene sequencing was done on samples that tested positive for HBsAg or anti-HBc.
- Overall, HBsAg and hepatitis B core antibody seroprevalence were significantly lower among individuals born after the start of the nationwide vaccination program in 1984.
- However, HBV core antibody and isolated surface antibody prevalence rose with age:
o 10-14 years of age: 0.4% and 43.7%, respectively;
o 14-18 years of age: 1.9% and 55.4%, respectively;
o 18-21 years of age: 8.1% and 59.6%, respectively.
- In addition, there was a large increase in the percentage of people testing positive for HBV DNA at 18-21 years of age compared with younger ages:
o From 0.2% to 3.0% for all eligible patients;
o From 0.3% to 5.7% for patients who received at least 3 vaccine doses.
- 5 of 8 fully vaccinated individuals who tested positive for HBV DNA had virus with mutations in the S (surface) gene.
Based on these findings, the study authors concluded, "Universal vaccination effectively controls HBV infection in children and adolescents.
However, they added, "after adolescence, there is a significant increase in the seroprevalence of anti-HBs, anti-HBc, and HBV DNA, indicating that new preventative strategies are needed for adults." Further, they advised that monitoring HBV prevalence using sensitive HBV DNA assays beyond adolescence is "mandatory" in the vaccine era.
R van Houdt, SM Bruisten, AG Speksnijder, and M Prins. Unexpectedly high proportion of drug users and men having sex with men who develop chronic hepatitis B infection. Journal of Hepatology 57(3):529-533. September 2012.
S Shahmoradi, Y Yahyapour, M Mahmoodi, et al. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. Journal of Hepatology 57(3):515-521. September 2012.
MW Lai, TY Lin, KC Tsao, et al. Increased seroprevalence of HBV DNA with mutations in the s gene among individuals greater than 18 years old after complete vaccination. Gastroenterology 143(2):400-407. August 2012.