How To Fight Treacherous Hepatitis B

Those infected with hepatitis B often don't know it, because they can go without symptoms for years. Looking at adults in the U.S. group most likely to be infected with hepatitis B - Asians and Pacific Islanders - the Stanford researchers created a mathematical model that found the most effective strategy is to screen this group to identify those who are chronically infected.

Those who are infected require lifelong management, including screening for liver cancer and possible treatment with antiviral medication.

Hepatitis B is 100 times more infectious than AIDS and about 10 times more prevalent worldwide, striking Asia particularly hard. One out of every 250 people in the United States has chronic hepatitis B infection, but studies estimate that among foreign-born Asians, the rate is one in 10.

"I don't want to tell any more 30-year-olds that they are going to die and there is nothing I can do," said Samuel So, the Lui Hac Minh Professor and a professor of surgery, one of the study authors.

Chronic hepatitis B infection often has no symptoms until it causes liver cancer or, after years of attack by the patient's immune system, causes so much scarring of the liver that it fails. And the infection often strikes young, otherwise healthy adults. About 60 to 80 percent of liver cancer worldwide is caused by chronic hepatitis B infection, according to World Health Organization estimates.

So founded the Asian Liver Center at Stanford more than a decade ago to educate, vaccinate and screen thousands of people vulnerable to hepatitis B infection in the San Francisco Bay Area, nationwide and in the Philippines and China.

Although current U.S. policy calls for newborns to be vaccinated against hepatitis B, So wanted to identify the best ways to protect those who missed their childhood vaccinations, especially the many foreign-born Americans from areas where hepatitis B is endemic, such as Africa, Eastern Europe and Asia.

So teamed up with Margaret Brandeau, PhD, a Stanford professor of management science and engineering, and a graduate student in her department, David Hutton, to develop a model to explore the costs and benefits of vaccination and screening.

"He knows so much about hepatitis B and we know a lot about mathematical modeling and cost-effectiveness analysis," said Hutton, who is the lead author of the publication. "When you put the two together, it seemed like a really great fit."

This analysis built on results published earlier this year by So and Stanford medical student Steven Lin. They screened more than 3,000 Asian-Americans at community-based events and clinics in the San Francisco Bay Area, and found that two out of three Asian Americans who are chronically infected with hepatitis B were not even aware of it. So said that demonstrated for the first time the importance of routine hepatitis B screening, and he wanted to find the most cost-effective way to do that.

"Initially we were just going to look at vaccination, and we almost stumbled upon this idea of screening and treatment," said Hutton. A quick blood test can determine if a person is infected, and is the only way to identify patients early for treatment.

The interesting thing, the authors said, is that identifying those who are chronically infected - rather than vaccinating all adults - turned out to have the most benefit.

"In retrospect, it makes sense that you want to identify the people who are chronically infected by screening," said Brandeau, the senior author of the study. Adults' immune systems are well-developed, so they run much less risk of acquiring chronic hepatitis B than do newborns and children. "But we didn't know that going in, and that was a real benefit of using a model," she said.

Their model also found, once a chronically infected individual is identified, there was a large benefit from vaccinating family members and others who have close contact to prevent the spread of the infection.

The model's estimate for the scenario of screening, treating those infected, and vaccinating close contacts was $39,903 per year of quality-adjusted life gained. "Quality-adjusted life" is a way of quantifying the benefit of a medical intervention by measuring added years lived, adjusted by the quality of those years. To put that number in perspective, So said, the cost-effectiveness of screening for hepatitis B is similar to the cost-effectiveness of HIV screening in the American adult population, which the U.S. Centers for Disease Control and Prevention has recently recommended.

"All of the evidence is falling into place," So said. "We have big ambitions to form a global hepatitis B initiative to eradicate hepatitis B from the face of the Earth." This study shows that to make that work, it is critical to screen adults from endemic areas to find those who are chronically infected and give them appropriate medical management so they won't die from it.

With So's leadership, the Asian Liver Center has advocated and helped to introduce legislation in California and in Congress that would support hepatitis B screening and immunization, and increase research that would improve detection and treatment options. So also consults for the CDC on policy advisories.

His ambitions fit right in with what Brandeau and Hutton want to do. Their next modeling project is with So, looking at the cost-effectiveness of the various catch-up vaccination strategies to protect the approximately 400 million children in China from hepatitis B.

In his biggest effort yet, So is also launching a campaign in a distant corner of China this fall, partnering with public health professionals and the government to vaccinate half a million children against the virus. China has the greatest burden of chronic hepatitis B and liver cancer in the world, So said. He was in Qinghai, a province neighboring Tibet, in early September to watch the first group of school children get vaccinated.

"It's a no-brainer," So said. "If we could vaccinate everyone, in 10 years we could have no new infections - it's just so simple."

Brandeau and Hutton hope to show the effectiveness of such a strategy with their mathematical skills. "I really want to create models that can influence policy, using operations research, systems analysis, and mathematics for the public good," said Brandeau. "We have the same goals."

Their findings will be published in the Oct. 2 issue of Annals of Internal Medicine.