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Samuel So, MD, FACS: "Eliminating the Voodoo from Hepatitis B"

Samuel So, M.D., FACS, the featured Keynote Speaker at the 3rd Annual B Informed Patient Conference: A Gathering of Friends (July 2002), presents "Eliminating the Voodoo from Hepatitis B". This presentation provides useful, easy-to-understand answers to common questions surrounding hepatitis B management and treatment.

The annual B Informed Patient Conference, sponsored by the Hepatitis B Foundation and the Hepatitis B Information and Support List, draws attendees from around the world and is the only conference geared specifically toward hepatitis B patients and families.

Dr. So is the Director of the Asian Liver Center and Liver Cancer Program at Stanford University, Stanford California, and is also the leader of the well-known Jade Ribbon Campaign, a national hepatitis B awareness effort. Additionally, Dr. So is a professor in the Department of Surgery at the Stanford University School of Medicine.

1. I have been affected by Hepatitis B. How can I become an advocate and help others with this disease?

You are not alone. I feel in this environment, with 1.3 to 1.5 million people in this country with hepatitis B, we actually have more people with hepatitis B than HIV. And just look at how successful HIV advocacy has been. You could actually be the beginning of a very strong advocacy group. We need you; we need you to speak out, talk to your congressmen, your legislators. Let's educate them about this problem, because they are totally oblivious to it. I spent time with my congressmen a few weeks ago, because he had no idea about this problem. But once you educate them, they are very interested in addressing this problem.

2. Why is the hepatitis B virus called the silent killer?

I got involved because I realized this was such a big problem - but, I asked myself, why should I as a surgeon become an advocate? Aren't there tons of liver specialists? Yes, but the problem is there is no money. I call hepatitis B and liver cancer the Silent Killer in Asians and Asian Americans - 1 in 10 are infected, and in some coastal areas of China, even 2 or 3 out of 10 are infected. Very often, they don't even know they are infected. The problem is that a lot of the doctors aren't aware of the prevalence, and they are not up to date on the latest treatments. They feel that there is nothing you can do about it, so they don't give patients the right information on how to take care of themselves. This is a disease that kills a million people a year. It ranks as the #10 or #11 cause of death in the world. It kills a million - which, my calculations, means that it kills 1 person every 30 seconds. But how many times do you hear people talk about hep B? No one writes about it, no one talks about it. That's why I want to energize you and help you figure out what you can do in your local community - write to your local newspaper and get someone to do a story about hepatitis B.

3. Why isn’t hepatitis B recognized as a problem by the US government in the way that hepatitis C is?

The problem is that in this country as a whole, the incidence is low. If you look at CDC data, the incidence is only 1 out of 1000. In Asian Americans it is about 1 out of 10. It is a problem for those in high-risk environments, such as those who undergo kidney dialysis, or doctors and dentists. A lot of people thought the vaccine would stop the problem, but unfortunately, there are millions of people who did not have access to the vaccine, or who were infected before it was available. This is why I want you all to become more active as advocates.

4. Why is Hepatitis B such a problem with Asians?

For those of you who have chronic hepatitis B, you basically are part of this group, which is a humongous problem in the world. Just imagine, there are 400 million people in the world with hepatitis B, compared to 40 million with HIV. So, the reason it is particularly a problem is because 75% of them, about 300 million, live in Asia. This is a big problem for Asians and Asian Americans, because most Asian Americans are recent immigrants. Most Asians became infected perinatally, from mother to child. So, next time you go to a Chinese restaurant, and sit with 12 people, chances are one or two of them have hepatitis B, and don't even know it, because their doctors never tested them. Why is this so dangerous? Because, as you know, if you are not monitored or screened for cancer, 1 in 4 will eventually die from liver cancer or liver failure. This is even higher in men than women - a large study in Taiwan found that the lifetime risk of hepatitis B for men was 50%.

5. Can the vaccine protect someone who has close contact with a chronically infected person?

You have to make sure that you develop the antibodies after vaccination, because there is about 5% of the population that is unable to make antibodies in response to the vaccine. Once you are vaccinated and you know that you have the antibodies, you are fine.

6. Should adolescents and adults be vaccinated against hepatitis B?

Absolutely - we have started a campus campaign for the college kids. If you look at a lot of the states, they did not implement hepatitis B vaccination until recently. Still, among high school seniors in California, which is a progressive state, probably 30% of them are unvaccinated, because they missed the cut off for vaccination.

7. Do you recommend universal vaccination and screening of high-risk groups?

I recommend universal vaccination, but especially in the high-risk community, like the Asian community, you should be screened first. I get emails about overseas adoption, but they never test the children, and they wind up with liver cancer at the age of 20. They feel protected when they are really not.

8. Why is the term 'carrier' misleading?

Carrier is a terrible term, and it ends up hurting a lot of people, because it gives them a false sense of security. You would never call someone with HIV or hepatitis C a carrier. We all want to get rid of this term. Basically, if you are a carrier, you have chronic hepatitis B. You could have normal ALTs (liver enzyme levels), and you might look healthy - years ago, people would refer to this as being a "carrier", but these are the same patients that get referred to us for liver failure or liver cancer, if they are not screened.

9. Why is it inaccurate to refer to a person with chronic hepatitis B (HBV) as a 'healthy carrier'?

There is a lot of misconception even among the physician community - many think that carrier is more benign - this is a big "voodoo" - they think because your ALT's are normal that you are a "healthy carrier" - this makes you let your guard down in terms of screening for cancer. So, once you have hepatitis B, you run the risk of getting liver cancer, and that is the population that needs to be screened.

10. What are the available treatments for hepatitis B and what are they used for?

There are two types of drugs - one we call the immune modulator (interferon) and one is the antiviral, which actually suppresses the virus from multiplying. So if you don't have a lot of virus (less than a few hundred thousand), then you don't want to use the antivirals. If your ALT is 80 and your viral count is a few million, then the rationale for treatment is to prevent further damage to your liver so that you hopefully do not develop cirrhosis, and also hopefully that it will decrease the incidence of liver cancer (although this has not yet been proven in hepatitis B, but it has in hepatitis C).

11. Who needs a liver biopsy and who doesn't?

There is an old school of liver specialists who believe in biopsying everything. And there is a new school who feels that we have enough data now, so why do we need to biopsy, because it is not going to change our treatment? I subscribe to the new school - unless you are going to enroll in a clinical trial, where you are required to have a biopsy.

12. What are the guidelines for evaluating treatment among chronic carriers with elevated ALTs (liver enzyme levels)?

If you come to my office, and your ALT is 80 (normal is 40) then I would proceed to check your hepatitis B virus DNA level. If your ALT is normal I won't even check the DNA level, because this test costs a few hundred dollars. If your DNA is a few million, then this is most likely a sign of active liver damage - if your viral count is high and your ALT is twice above normal, then you can gather that the elevated ALT is being caused by the virus.

13. Should the e-antigen be used to determine the success/end point of treatment?

If you actually look at a lot of the Asian patients who have been infected a long time, they are already seroconverted to e-antibody positive and e-antigen negative, and their DNA level could still be very high. When I was on the FDA committee for the lamivudine approval hearing, I raised this point. For those with long-term chronic infection, using the e-antibody seroconversion may not be the best way to determine the endpoint of treatment, because a lot of people will already have this conversion, and they are still at high risk for liver cancer. For those with a recent infection, the seroconversion as endpoint works better. I think that in general, using the e-antigen conversion to assess the endpoint of treatment should be re-examined.

14. How do you determine which treatment should be used, and for how long?

When I try to look at it objectively, the first thing you have to do is weigh the side effects - interferon has more side effects, and lamivudine and adefovir are very patient-friendly. There are three prognostic markers for treatment with interferon: viral load (those with a lower load usually respond better), ALTs (those with higher levels usually respond better), and duration of the infection (those with shorter duration have a better response, usually). Most Asian patients do not meet these prognostic indicators for treatment with Interferon. Once again, I look at hepatitis from an infectious disease point of view - it is a chronic infection, and might need chronic suppression (long-term) just like HIV or diabetes.

15. Do you recommend treating patients with a high-viral load and normal ALTs (liver enzyme levels)?

We will probably end up recommending treatment for people with high viral loads and so-called normal ALTs, because the normal ALT level is not accurately reflecting what is happening to the liver. Also, what do you call normal? Normal is probably 16-18 - to me even the upper limits of what some people call normal (such as a level of 40) is abnormal, because normal should really be about 20 or less. Because looking at ALT levels alone is not enough, we will probably wind up like HIV - looking at the viral load.

16. How often should someone with chronic hepatitis B be screened for cancer?

Ever since Taiwan adopted universal vaccination, they saw a significant decrease in childhood (children less than 15) liver cancer. Most people develop liver cancer about 20 years after they have been infected. If you were infected at 20 or 25 from a blood transfusion, I would suggest that you should start getting screened in your 40's - this is not the normal recommendation. Once you develop cirrhosis, you need to be screened regularly (twice a year).

17. What tests are used to screen for HCC (hepatocellular carcinoma)?

Twice a year AFP tests, and twice a year imaging studies as well.

18. Can someone with normal ALTs (liver enzyme levels) develop liver cancer?

Yes, because the cancer is caused by the virus causing genetic changes, which is quite different than talking about the physical damage to your liver. Right now, we can't predict who with chronic hepatitis B will develop liver cancer and who won't, and this is why we need more screening programs.

19. What tests are recommended for people with chronic hepatitis B?

If you don't have cirrhosis, just chronic hepatitis B, we recommend from the age of 30 (we choose 30 because if you look at the liver cancer rates for this country, the liver cancer rates start go up at 30, especially for those with chronic hepatitis B from childhood), twice a year AFP level and once a year ultrasound. If you rely only on the AFP, you will miss half the liver cancer. AFP will only pick up about 60% of the cancer - you need the imaging study to pick up the lesions - it is just like breast cancer - early detection gives you a better chance of surgical removal of the tumor and a better chance of long-term outcome.

20. Why is ultrasound used?

Ultrasound is done purely to screen for cancer. It is not the best test, but it is the cheapest one, and it is non-invasive. Once you have cirrhosis, ultrasound is not the best test to use to screen for cancer.

21. How do the ALT (liver enzyme levels) and AFP (alpha-fetoprotein) tests differ?

Just remember: ALT monitors evidence of active damage; AFP is the screen for liver cancer, and many doctors don't do this test in the normal liver panel. It is so tragic when the AFP is never checked, because the ALT level does not tell you whether there is cancer.

22. What liver cancer screening should be done in people with normal ALTs (liver enzyme levels)?

I would say if you have chronic hepatitis B or C, from a public health standpoint, we advocate screening beginning with the age of 30 for those who have the virus from childhood.

23. What is the prophylaxis treatment to prevent hepatitis B (HBV) recurrence after transplant?

As long as they use the right combination of protocols to prevent recurrence. The way we do it is right at the time of transplant, we give them a big dose of hepatitis B immune globulin (HBIG), and we keep up the dose for about 7 days, and we also give some lamivudine. In the population that does not have a high viral load, just using immune globulin will cause a very low recurrence rate. But HBIG is expensive. But if you just use lamivudine without HBIG, the recurrence rate is much higher, so you have to use the HBIG. You are looking for a certain level of HBIG in the blood, and very often with patients, after one or two years, you can drop the dose to maybe once every 6 weeks.