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W. Thomas London, MD: "Why is Hepatitis B important?"

Dr. W. Thomas London was a keynote speaker at the B Informed Educational Forum Program held in New York on September 23, 2004. For more than three decades, W. Thomas London M.D. has been a national leader in the effort to unleash the secrets of the hepatitis B virus, which has infected one in 20 Americans and chronically infects 1.25 million. Dr. London specializes in researching how hepatitis B impacts the liver, and how this viral infection promotes liver cancer. Over the course of his varied professional life, he has written about hepatitis B from the perspective of an epidemiologist, a clinician and a virologist.

Dr. London is a senior member, focusing on viral hepatitis in the Division of Population Science at the Fox Chase Cancer Center in Philadelphia. This division identifies groups of people with high cancer risks, such as those with hepatitis B, to develop community-based strategies to help people reduce their cancer risks and detect cancer early. The division also studies how environmental agents and genetic factors interact to predispose people to cancer.

Until recently, Dr. London was also an adjunct professor of epidemiology at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine and associate editor of Cancer Epidemiology Biomarkers and Prevention. He is widely published in peer-reviewed publications.

Dr. London received the Distinguished Scientist Award in 1998 from the Hepatitis B Foundation in Doylestown, PA, and the Distinguished Interdisciplinary Research Award in 1999 from the American Cancer Society, Southeast Region. He sits on the Board of Directors of the Hepatitis B Foundation and is a member of the National Institutes of Health Reviewers Reserve.

1. Why is Hepatitis B important?

What I want to do in this short talk is to tell you why hepatitis B is still important. And the reason I say still important is because we’re all kind of flooded with information about hepatitis C and HIV. Although hepatitis B was kind of the headline story maybe fifteen or twenty years ago, as hepatitis C has risen in not just prominence, but in probably a broader spectrum of the American population is infected with hepatitis C than with hepatitis B. As you’ll see, there are particular groups of people in the United States who seem to be more likely to be infected with hepatitis B, whereas hepatitis C has a big behavioral element and behavioral element crosses all parts of the population.

2. What is the global impact of HBV infection?

So the first thing I’d like to get across is what is the global problem? The global problem is that there are at least 350 million people in the world chronically infected with hepatitis B virus and that’s somewhere around six percent of the world’s population. So we’re talking about a major illness. It’s been estimated by the World Health Organization that about one million people out of these 350 million people will die each year of either of HCC as a kind of cellular carcinoma or liver cancer or chronic liver disease. And of these 350 million, if we didn’t add any new carriers to the population, any new chronically infected people, which we’re doing every day, sixty million would eventually die. Just to put sixty million in perspective, that’s more than died in all of World War II. So, we’re talking big numbers and a lot of tragedy.

3. What is the global incidence of liver cancer?

In the year 2000, there were about 550,000 new cases of liver cancer and because the treatment for liver cancer especially in the great bulk of the world, is so poor - almost all the people who get liver cancer die from liver cancer. So you can see that the mortality figure and the incidence or new cases are almost the same. Even though there have been strides made in Western countries primarily with the use of liver transplantation - to improve the outcome of people who are discovered with early liver cancer for the great bulk of the people in the world, there is no adequate treatment for liver cancer.

4. What is the origin, pattern, and development of liver cancer?

So if we say that liver cancer causes about 550,000 deaths per year that’s the fifth largest number of cases of cancer in the world among men. It’s the third biggest cause of cancer death among men in the world. And for women, it’s number eight in incidence and number six in mortality. And about eighty percent of these cases are caused by hepatitis B, fifteen percent by chronic infection with hepatitis C, and five percent by other causes.

5. What is the difference between acute and chronic infection?

I'm not going to spend a lot of time on the difference between acute and chronic infections because the other speaker will deal with that. But I just wanted to give you a sense of the difference. Acute infections are short term. They last no more than six months by definition. It’s not that they don’t sometimes last longer, but by definition they don’t last more than six months after onset and it’s terminated because there’s an adequate immune response to the virus. And the important thing is that there does not appear to be any increased risk of liver cancer for people who have an acute infection and get over it. But chronic infections last for years and they do carry the increased risk of chronic hepatitis, cirrhosis, liver cancer, and death.

6. What is the relation between age and chronic infection?

It depends on the age at which you get infected in terms of the probability that you are going to have a chronic infection. If you’re infected at birth or in the first few years of life, then you have an extremely high risk of developing a chronic infection. One of the reasons that in China there are very large numbers of hepatitis B carriers is that mothers are infected. They infect their babies at birth or shortly after birth. And ninety percent of those babies go on to be chronically infected usually for their lifetime. And that decreases as you get older. So from one to five years, thirty percent of children who are infected develop chronic infection. But after five years, that falls to five or six percent.

7. What is the global pattern of chronic infection?

You can divide the world up into places where there are a very high percentage of the populations who are chronically infected with the virus. And this is again World Health and CDC definitions, but if you have more than eight percent of the population who are chronically infected, they are considered a high prevalence area. If it’s two to seven percent, that’s considered an intermediate area and if it’s less than two percent, that’s low.

8. What is the geographic distribution of chronic infection?

If you’re in a high area, your lifetime risk of getting infected is higher than sixty percent. And for most of those areas, it’s up to eighty or ninety percent. If you’re in an intermediate area, then your lifetime risk of infection is somewhere between twenty and sixty percent. And if you’re in a low risk area, your risk is less than twenty percent. So in the high risk area people get infected as young children. In the intermediate area, you have some people getting infected as young children and some getting infected at older ages. And in the low risk area, almost all of the infections are adults and usually because of one risk behavior or another. So, these are the areas of the world where you find the high, intermediate, and low risks and you can see that the red areas cover large parts of East Asia, Southeast Asia, Sub-Saharan Africa. The band in South America are South American Indians. It’s not the European populations that are infected and so it’s actually the Amazon Basin where the Indian populations have twenty percent or higher prevalence of hepatitis B. And the same is true for Northern Canada, Alaska, and Greenland; those are by and large either Indian or Inuit populations. And the intermediate populations in yellow, a lot of Eastern Europe and the Soviet Union still have pretty high prevalence of chronic carriers.

9. What is the incidence of liver cancer in males?

If you look at where you find liver cancer, you can sort of overlap the maps between the places where there were a lot of hepatitis B carriers and where there’s a high incidence of liver cancer. So, China, Sub-Saharan Africa, and some parts of the Soviet Union as well.

10. What is the global prevalence of chronic hepatitis C?

Although the map for chronic hepatitis C infections looks a little bit like the map for hepatitis B actually the red areas, the highest areas of hepatitis C don’t conform to the liver cancer map. The area in Africa with the highest hepatitis C infection rate is Egypt and that’s because when people are treated for schistosomiasis in Egypt which is sort of the most common disease they used injections that had contaminated needles and they spread hepatitis C all through the population.

11. What is the incidence of chronic HBV in the US?

Okay, let’s come to America. We have somewhere between 1.25 and 1.3 million chronically infected people. Half of all the carriers in the United States belong to either the Asian and Pacific Islander population or they’re African immigrants recent African immigrants, not the African American population that’s been here for generations. The overall prevalence of hepatitis B carriers in the general United States population is three per thousand or three tenths of a percent. But in the Asian and Pacific Islander population and among African immigrants, the prevalence is anywhere between five and fifteen percent. So, there’s a real skewing of who is most likely to be chronically infected.

12. What are the US risk groups?

Among people in the United States, who are the ones who are most likely to develop a new infection? A lot of these are behavioral. So people, both men and women who have multiple sex partners, men and women who have a sexually transmitted disease, men who have sex with men (which is CDC talk for gay men) sex contacts of infected persons - heterosexual or homosexual - people who use drugs by injection (illicit drugs) the household contacts of chronically infected people, infants born to infected mothers, infants and children born into the high-risk populations the Asian and Pacific Islanders and African immigrants, and then at considerably lower risk healthcare workers, public safety workers. Last on the list, we have hemodialysis patients. There was a time in the early 70’s where hepatitis B was absolutely rampant among hemodialysis patients but with the good hygiene, careful use of the dialysis machinery, and primarily use of vaccination of people with chronic renal disease, that’s really almost been eliminated.

13. What are the current and future challenges?

So, what are the challenges? Well, there’s still a lack of understanding of the risks of chronic infection by both the public and sadly by healthcare providers. A lot of doctors really are still not very clear on how you get hepatitis B, how you treat it, how you manage it. It’s still an area that requires more education. Then, research is needed to find a cure of chronic hepatitis B virus infection. You’ll hear more about the treatment of hepatitis B, but the fact remains that in 2004, we still don’t have a therapy that is curative. We can manage people quite well, but it’s difficult to cure them. And so, what I've tried to lay out is that this is a very large problem and for those of us in the field, we see that there are not enough research funds to address the remaining problems. Funding has either plateaued or actually declined (the federal funding). The likelihood is in the next several years as the budget crunch really hits, not just this kind of research but all medical research, funding is going to decline for many diseases. The National Institutes of Health is going to be making choices, making priorities, which diseases are favored and which diseases are not. The ones that are not favored are going to see their funding diminished greatly. And so this is a critical time where we think it’s really vital to make the case that hepatitis B is still not just a very important problem but a major cause of morbidity and mortality in the world at large and a significant problem in the United States.