Mutant’ HBV cases cast doubt on e-antigen policy
Four patients infected by HbeAg-negative surgeons
Researchers in the United Kingdom have documented hepatitis B virus transmission to patients from four surgeons who did not have the widely accepted "e antigen" (HBeAg) marker for infectivity, further complicating the issue of managing infected providers.1
In both the United Kingdom and the United States, recommendations on restricting the practice of HBV-positive health care workers who perform invasive procedures are based on the presence or absence of HBeAg, which is associated with a high titer of circulating HBV in the blood and therefore greater infectivity. HBeAg has been a strikingly accurate marker for infectivity in such cases, as virtually every documented transmission prior to the UK report has been ascribed to a health care worker who carried the e antigen.2
Double gloving not consistently practiced
The UK report documents transmission from four HBV-infected surgeons to four patients, all of whom recovered without developing fulminant hepatitis. The cases of transmission occurred without any reported exposure incidents or obvious breaches in infection control. However, double gloving thought by some epidemiologists to be an important measure of protection for both surgeons and patients was not consistently practiced by any of the physicians in question.
Regardless, the report underscores that policies relying on HBeAg as a definitive marker for infectivity may not prevent all cases of transmission to patients. Beyond that, the policy implications are less clear, for the cases involve an HBV "precore mutant" strain that is not easily identified and can mask the infectivity of the worker, explains J.E. Banatvala, MD, professor of clinical virology at St. Thomas Hospital in London and chairman of the UK’s Advisory Group on Hepatitis.
"This particular precore mutant means that the virus can no longer make e antigen, but it still retains its infectivity," he tells Hospital Infection Control. "You might say, why don’t you look for the mutant? The problem is that the mutant is inherently unstable, i.e., it’s not there tomorrow but it is there next week."
The UK clinicians noted that it is not known how many carriers of HBV have the precore mutation strain. Even if they could be reliably identified, another problem is that not all carriers of the mutant strain will necessarily be as infectious as the surgeons proved in the UK cases, says Craig Shapiro, MD, medical epidemiologist in the hepatitis branch of the U.S. Centers for Disease Control and Prevention.
"You can be infectious when you have the strain even though you are not e-antigen positive, but it doesn’t necessarily imply that you are [always] infectious if you have the strain," he says. "Also, to determine whether you have that strain it almost requires research laboratory techniques. It is not the standard diagnostic test that you give from any clinical laboratory like you can for the e antigen."
No U.S. changes expected
In light of such uncertainties, the CDC plans no immediate changes in U.S. policy, which essentially advises surgeons to know their HBV status, and if positive, to determine if they have HBeAg. If they are carriers of the e antigen, they are to go before state and local expert review panels regarding their continuing practice. The CDC recommends HBV immunization, but has no regulatory authority to require it. The policy used in the UK is considerably tougher, which is one reason the cases were identified, Banatvala says.
Since 1993, UK surgeons and other health care workers at risk for HBV infection have been required to be vaccinated, and their subsequent immune response to the vaccine must be documented. Surgeons who do not show a sufficient antibody titer against hepatitis B surface antigen are further investigated, and those in whom HBeAg is detected are not allowed to perform procedures involving a risk of exposure. Carriers in whom serum HBeAg is not detectable may perform such procedures unless they are associated with the transmission of HBV. Of the four cases reported, three were identified after the introduction of the current guidelines in the UK and the fourth was originally investigated in 1988, according to the UK study.
"As you begin to implement guidelines, get people vaccinated, and your surveillance gets better, crawling out of the woodwork are the unusual cases," Banatvala says. "What are the options available to us? One is to do nothing. Please bear in mind that most countries are not doing anything at all, even implementing the vaccination policy."
Extreme measures could create waiting lists
A second option would be to ban all HBV carriers regardless of antigen status from practicing exposure-prone procedures, but such an extreme measure could prohibitively reduce the number of practicing surgeons and could result in patient waiting lists for certain procedures, he says.
"One thing we are very concerned about is having people suffer complications and die on a waiting list," he says. "So you have to equate that with the very rare risk of transmission of a mutant."
An option that will be explored immediately is attempting to measure HBV infectivity in HBeAg-negative surgeons with molecular diagnostic techniques like polymerase chain reaction to assess viral load in the blood. It is also possible to reduce infectivity and sometimes the HBV carrier state through interferon treatments, he says.
The findings also underscore the value of obtaining an adequate clinical history from patients with acute HBV. The UK investigators suggest that a history of surgery in the six months before the onset of infection in the apparent absence of other risk factors should lead to a review of the HBV status of members of the implicated surgical team. If a member of the team is found to be HBV-positive, a negative result of a test for serum HBeAg is no longer sufficient to rule out a surgical team member as the source of the patient’s infection, they conclude.
1. The incident investigation teams and others. Transmission of hepatitis B to patients from four infected surgeons without hepatitis B e antigen. N Engl J Med 1997; 336:178-184.
2. Centers for Disease Control and Prevention. Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. MMWR 1991; 40:1-9.