Office of Research & Development
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Navy Veteran Natale Stella (left), seen here with Dr. Lauren Beste, has lived with hepatitis B for two decades but has never experienced any symptoms. (Photo by Chris Pacheco)
November 6, 2019
By Mike Richman
VA Research Communications
To what extent does military exposure, including time in combat, put someone at risk for acquiring hepatitis B? The virus causes a liver infection that, if not treated properly, can lead to serious health consequences, such as cirrhosis—a deterioration of the liver—liver cancer, or even death.
Potential military contributors to hepatitis B have not been thoroughly explored, especially those related to combat exposure, blood transfusions, or travel to regions where the hepatitis B virus occurs at a high rate. Now, a new study finds Veteran prevalence of hepatitis B to be greatest among those with traditional risk factors, such as drug-use or high-risk sexual practices, but also suggests that combat exposure can be a risk factor on its own. Hepatitis B can be acquired, for example, by being wounded or making contact with infected blood when a fellow service member is wounded.
"You can suppress it, but you can almost never get rid of it once you're chronically infected."
Dr. Lauren Beste, an internist at the VA Puget Sound Health Care System in Seattle and a senior official in VA’s HIV, Hepatitis, and Related Conditions Program Office, led the research. She believes the study, which appeared online in the journal Clinical Gastroenterology and Hepatology in August 2019, is the first to gauge the prevalence of hepatitis B in relation to combat.
Her study included 1,146 Veterans who received VA care from 1998 to 2000. Estimates of hepatitis B among VA users before the 21st century were based on laboratory results and administrative data from the less than 30% of patients tested for the virus in the course of standard medical care.
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Beste and her team found that evidence of hep B exposure was highest among Veterans with traditional risk factors, such as drug use or high-risk sexual practices. Of these people, 60% reported a history of combat exposure. After adjustment for demographic and traditional risk factors, the researchers determined that service in a combat zone and being wounded in combat were independently associated with exposure to hepatitis B.
The study team concluded that more research is needed to determine whether Veterans who were in combat prior to the era of universal vaccination should be screened for exposure to hepatitis B. The military began vaccinating all service members for the disease after 2000. Vets who have served in the 21st century are presumed to be vaccinated and thus protected from the virus.
“The hepatitis B virus has effective treatments and can be identified with a simple blood test, but military service is not one of the risk factors that is traditionally used to prompt screening,” says Beste, who is also an assistant professor at the University of Washington. “There are many important reasons to study whether military exposures are linked to hepatitis B. One is to make sure we offer screening to Veterans who could be at risk. Another is to give Veterans a chance to apply for VA compensation if their hepatitis B is related to military service.”
It’s important to note that the study does not show cause and effect, only an association between combat and hepatitis B. The researchers can’t prove definitively that any case of hep B came about because of a combat wound or contact with infected blood in a combat setting.
"This kind of study cannot prove a causal relationship," Beste says. "We can only prove that combat and hepatitis B exposure are somehow linked. In lay terms, somebody with blood evidence of hepatitis B exposure is saying, `No, I didn't inject drugs. No, I didn't engage in risky sex. No, I didn't have an occupational needlestick injury. But I was in a combat situation.' The association between combat and hepatitis B relies on the accuracy of responses from people to the questions about risk factors. That said, combat seems to be an independent risk factor based on the data we have available. Furthermore, as a physician, my job is to identify who needs to be screened for hepatitis B, regardless of the way the hepatitis B exposure may have occurred. From a practical standpoint, Veterans with combat history do appear to have an increased risk for hepatitis B exposure."
The hepatitis B virus is transmitted when people come in contact with the blood or bodily fluids of someone else who has the virus. This most often happens through sexual contact or the sharing of needles, syringes, or other drug-injection equipment; or from mother to baby at birth.
Hepatitis B can be either acute, generally meaning the virus will leave a person’s body within the first six months, or chronic, in which case it never goes away even if treated. “It’s important to identify the people at risk in order to treat them and hopefully prevent the long-term consequences of the disease,” Beste says.
The three most common types of viral hepatitis are A, B, and C. Of the three, hepatitis C is most prevalent in the Veteran population and has received much more media coverage and attention in the research community. VA has treated some 120,000 Veterans infected with hepatitis C; more than 100,000 have been cured.
“These high cure rates are largely the result of important new breakthroughs in medications to treat hepatitis C,” Beste explains. “In particular, VA has received much media exposure for its large-scale hepatitis C treatment program. It’s important to remember that outside of the United States and other developed nations, hepatitis B is much more common than hepatitis C and far surpasses hepatitis C as a cause of liver cancer and liver-related deaths. The hepatitis B infection is a global health care problem [see sidebar], especially in developing areas.”
Unlike hepatitis C, hep B is not curable. In that sense, it’s like the human immunodeficiency virus (HIV), a sexually transmitted infection that can cause AIDS, in that “you can suppress it, but you can almost never get rid of it once you’re chronically infected,” Beste says. “In most cases of hepatitis C, you can take pills, and it’ll be totally gone from your body.”
Hepatitis A is an important and growing cause of liver disease that has resulted in large outbreaks in the U.S. and has affected tens of thousands of people since 2014. “While hepatitis A does not cause chronic infection, it is extremely contagious and can cause severe acute illness up to and including liver failure and death,” Beste says. “The media excitement surrounding hepatitis C is well-deserved. But I hope for improved public awareness and research attention on A and B, both of which are vaccine-preventable.”
In the study, Beste and her colleagues used survey data and stored blood serum collected in a 2005 study on hepatitis C prevalence in Veterans.
In a 36-item questionnaire in the 2005 study, the Veterans self-reported on potential military and non-military risk factors, such as exposure to combat and to blood in combat; vaccination with pneumatic jet guns; drug use history; and sexual behavior. The participants also underwent blood tests that Beste and her team reanalyzed to determine the prevalence of hepatitis B infection, exposure, and immunity, before assessing the links between military risk factors and hepatitis B.
“We used the blood test results to tell whether someone’s been either exposed to hepatitis B or infected with hep B,” Beste says, “because a lot of people who are exposed don’t necessarily get a chronic infection. The blood tests can tell us if you’ve ever been exposed or are currently infected. By linking the risk factors and the blood test results, we were able to tell that combat is associated with hep B exposure, even after we accounted for more typical risk factors like drug use history and sexual history.”
Combat questions included:
Sexual behavior questions included:
Even though the interview was private and confidential, the researchers observed high rates of missing data on some of the questions related to sexual behavior. They thus combined high-risk sexual practices into a variable that was considered positive if one or more of the following exposures were reported: more than 20 sexual partners, unprotected sex with an injection drug user, unprotected sex for payment, or sex between men.
Significant information was also missing from the questions on military exposures, such as exposure to blood in combat and receipt of a blood transfusion. Since most people who were in combat likely reported it as such, the researchers chose to classify missing values as negative responses—indicating someone was not in combat—rather than removing the Veteran from the overall analysis.
“Our study represents an important step toward understanding hepatitis B risk factors and prevalence in Veterans and military service members,” the researchers write. “Overall rates of hepatitis B exposure are higher in VHA users compared to comparable age- and race-matched males in the U.S. Traditional risk factors account for the bulk of exposures. But the role of combat in the causal pathway for hepatis B exposure remains undetermined. Although a minority of individuals with adult hepatitis B exposure go on to develop chronic infection, 8.75 million living U.S. Veterans served in the pre-vaccination era. Hepatitis B screening among those with combat service prior to universal military vaccination could be justified, particularly if our findings are confirmed in future studies with more participants.”
Beste wasn’t surprised by the results but is unsure if VA will take action based on the findings, such as implementing routine hep B screening for older Veterans.
“Hepatitis B is a blood-borne disease that can be spread from mother to child, through sexual contact, or through blood contact, such as intravenous drug use and needlestick injuries,” she says. “Our finding that military combat was independently associated with hepatitis B exposure is not surprising, given the high degree of transmissibility of this virus.”
In addition to a larger sample size, she says a more detailed risk-factor questionnaire that focuses entirely on hepatitis B would be helpful in the future.
“Because we used survey data from a prior study that was designed to determine the prevalence of the hepatitis C virus, we lacked some elements that would have been helpful for hepatitis B,” she says. “Specifically, the questionnaire did not ask about birth country or parental birth country, both of which are pertinent to hep B.
“Also, many people chose not to answer questions that dealt with important hep B risk factors, such as sexual behavior or drug use,” she adds. “The questionnaire results were collected many years ago, but it’s hard to speculate on whether people would choose to answer those questions today. Times have changed about how the military responds to people who are involved with drugs. One might speculate that societal attitudes have also changed a lot toward sexual behavior. Maybe more people would be willing to answer those questions.”
About 30% of the global population has had exposure to hepatitis B, making it one of the most common viral infections in the world. Transmission from mother to infant is one of the most frequent ways the virus is acquired, especially in African and Asian countries.
“But that’s not necessarily true for people born in the United States for a variety of reasons,” says Dr. Lauren Beste, an internist at VA Puget Sound. “We vaccinate here and screen people during pregnancy to prevent mother-to-child transmission [see main story].”
Navy Veteran Natale Stella, one of Beste’s patients, is an exception to that U.S. trend. He believes he acquired the virus at birth from his mother, noting that his two older sisters also have hep B and contracted it the same way. His two younger sisters don’t carry the virus.
Stella has lived with hepatitis B for two decades but has never experienced any symptoms. He has been on several anti-viral medications, most recently tenofovir alafenamide (commercial name Vemlidy, among others). He sees Beste every six months for a checkup.
Stella served on two aircraft carriers during the Vietnam War. Even though he likely acquired the virus at birth, he has a military hook to his story.
“I’ve heard how mom got a hold of it during World War II,” says Stella, who is now 71. “She was given a blood transfusion after the Americans came into Italy. She was Italian. I don’t know why the Americans were doing it, but they did give her some blood. She wasn’t diagnosed until way later in life here in the United States. She was in her 60s at the time.”
Stella says his mother lived with the disease for about 20 years and was never treated for it before she died. He thinks she remained symptom-free.
--- Mike Richman
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