Everything You Wanted to Know...
Everything You Wanted To Know About HBV, But Were Afraid To Ask!
- Dr. W. Thomas London,Senior Member at Fox Chase Cancer Center, Phila., PA
- Dr. Minh Nguyen, Director of Clinical Gastroenterology at Fox Chase Cancer Center
- Dr. Ken Rothstein, Associate Director, Albert Einstein Center for Liver Disease, Phila., PA
- (Not Pictured) Dr. Eddie Cheung, Clinical Professor, /Hepatology UC Davis School of Medicine, Davis, CA
Saturday, July 9, 2005
This session was designed to be highly interactive with a panel of hepatitis B experts available to answer any and all questions from the attendees. There was no fixed agenda and Steve Bingham moderated this very lively and informative 90 minute dialogue! [Please note, questions were answered by different panelists, therefore, each bullet point represents a different doctor’s response] As an HBV carrier, how would I know whether I need treatment?
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As an HBV carrier, how would I know whether I need treatment?
- It sounds like you’re wondering how you will “feel” before requiring treatment. Most people feel OK, but nevertheless may need treatment. Once you feel “bad”, the liver disease could be quite serious. This is why you need to be regularly screened by your doctor.
- A treatment decision is based on inflammation (i.e. how high is the ALT?), viral DNA levels, physical exam, and perhaps a liver biopsy to see if there is any liver damage.
How often should I be seen by my liver doctor?
- Ideally you should see your doctor every 6 months, but there is no magic number. Some doctors want to see their patients every 2 months, but this is not realistic for everyone. Some doctors say once a year is fine. But in general, every 6 months is a reasonable recommendation.
Many patients experience “liver pain” on the right side – what causes this pain?
- There are many reasons a person might feel right sided pain, and think it’s the liver. Pain can be caused by stomach problems, ulcers, heartburn, constipation - all of these symptoms occur in the right upper quadrant, where the liver is. People with chronic liver disease might be more sensitive to this type of pain.
- 75% of patients periodically have pain or discomfort in the right or left side of abdomen. The use of mild analgesics - Tylenol or NSAID – might help with this pain.
What do you treat with, if at all, during the “immune tolerant phase”, when there is high viral load and little clinical evidence of disease?
- It is very controversial; take a “wait and see” approach since the data is unclear and there is always a concern about viral resistance.
- Agrees, but treatment is becoming more liberal – don’t always wait until the ALT is 100; can treat if ALT is lower and viral load is a bit lower because there are more drugs, and better drugs; can be more liberal about when to start therapy. The key is immune response potential, which is best measured by ALT. The danger of treating high viral load with an oral drug is that resistance is likely to develop. Therefore, treating with two drugs like lamivudine or entecavir and adefovir may make sense because the resistance to one drug will be offset by sensitivity to the other drug.
- This is a complicated decision. You can’t always rely on or look at the ALT; may need a liver biopsy for a better evaluation of the situation (for example, immune tolerant people with evidence of fibrosis may need to be treated even if they have low ALT). Interferon needs an immune response to work and there is the issue of viral resistance to oral anti-viral drugs, but with new medications, there are now and will be more alternatives.
If a 7 year old child has ALT 109 and a liver biopsy shows Stage II fibrosis, is this a point where there is obvious damage to the liver and is it time to treat?
- Stage II fibrosis means that you are halfway to cirrhosis and the elevated ALT reflects inflammation. This is significant in a child – there is a strong indication to treat and try to turn the disease into an inactive state. Interferons might be more effective in this case than the oral agents, but there is some toxicity and inconvenience. Interferon slows down progression of disease – this is a goal, to slow down the disease until better drugs come along to cure it. Would consider off-label PEG interferon since it’s been well tolerated in children with HCV. Whichever treatment is used, would try to be aggressive.
- Would probably start with interferon since it has a limited duration (usually 48 weeks) and there’s no risk of viral resistance. Not sure what the long-term effects the oral drugs would have on a developing child. Since some kids might have to take treatment for years, the drugs could affect renal function, and have other unknown developmental side effects. Agrees that the results for PEG interferon look good.
- In a young patient with a strong, motivated family and evidence of liver damage by biopsy, normal ALT and high viral load, interferon makes sense, especially because of the finite length of treatment. Knocking down the viral load will help physically and mentally.
What happens when a person has stage II fibrosis, has “e-Antigen seroconverted” (the eAg+ converted to eAg-), ALT is normal, and DNA is almost undetectable?
- There is no evidence for treatment with the available drugs right now. There are other factors that can impact fibrosis, such as smoking, increased age, alcohol, diabetes, being overweight, etc. However, this person is still at risk for liver cancer and needs to be screened closely – with ultrasound and AFP blood test at least every 6 months.
At what stage of fibrosis do you NOT recommend treatment with interferon?
- Age, medical conditions, inflammation, viral load, ALT are all taken into consideration.
- If someone comes in with low platelets, you hesitate to treat. If their bilirubin is high (which can indicate decompensated liver disease), would also not start on interferon.
Would you use PEG interferon in kids, even though it is not approved yet?
- Yes, it is used all the time in children with hepatitis C. Research seems to say that it is very well tolerated in kids.
If regular interferon is not successful, would you put an adult patient on PEG interferon?
- I would probably just go to the oral drugs.
If you are treated with interferon and it does not work, have you lost ground by being on it?
- There have been attempts to study this. Studies imply that a patient’s lifetime risk of HCC and cirrhosis is still lower with long-term interferon, even if it does not work.
Are side effects worse with PEG interferon vs. regular interferon?
- Patients say the side effects are the same as regular interferon, but they tolerate the PEG more easily because there is only one weekly shot (instead of 3 shots a week). Because PEG interferon lasts longer in the body, any side effects can be more severe, such as depression. With PEG, there is also a 10-15% increased incidence of pulmonary problems, such as pneumonitis. You need to have a good relationship with your doctors and be sure to tell them all of your symptoms to avoid problems.
Should I consider PEG interferon with a history of chronic HBV for 10 years, normal liver enzymes, e-antigen positive, normal liver biopsy 10 years ago, and DNA that is slowly increasing after being on Adefovir for two years (viral load was in the billions before treatment – went down to 182,000 - and now it is rising and up to 2 million)?
- Need to remember that people who respond best to interferon have signs of liver inflammation, which is confirmed by an elevated ALT – without signs of inflammation, there is a decreased chance of responding to interferon. In this case, it appears that resistance to oral drugs has occurred, and combined with a normal ALT, this patient is probably not a good candidate for interferon.
- Might consider switching to another oral agent before thinking of going to interferon. It looks like the virus is becoming resistant to oral treatment, so it might be time to switch drugs. There has never been a study about switching from oral drugs to PEG, so it is hard to have a clear answer. Since the oral meds became available, very few patients have chosen interferon because of the injections and side effects. The only studies compare PEG-interferon with lamivudine, but there are no studies of interferon treatment for people who fail oral antivirals.
- The key thing to remember is that your first treatment is probably your best shot at a cure.
A recent study compared regular interferon and PEG interferon, and it suggested that if you increased the dose of PEG interferon for heavier people, it might be more effective?
- Very controversial. Does seem to make sense, however, and some studies show that heavier patients do not respond as well to treatment as other patients. PEG interferon dosage is calculated on a person’s weight; whereas, regular interferon dosage is not dependent on weight. Certainly need more studies to answer this question.
With PEG interferon, if there are no side effects in the beginning, will they show up later?
- Most patients experience symptoms in the beginning, but some people do experience symptoms later during treatment.
I responded to PEG interferon and am now HBsAg- and HBsAb+. My doctor says that I’m “cured” and that he never wants to see me again. Does this make sense?
- Your doctor should continue to see you at least once a year since viral DNA and HBsAg can return. You are also still at greater risk for liver cancer than someone who has never been infected with HBV, so you should be screened for liver cancer every year.
- Although we do not know what the natural history will be in patients who lose the virus and develop surface antibodies, it is important to keep checking. Again, liver cancer is still a risk and should be screened for regularly.
I was on lamivudine for 3 years and lost my e-antigen; I tried stopping after a year, but converted back to e-antigen+ (I never developed positive e-antibodies and my DNA increased). So I went back on lamivudine and am now still e-antigen+ with a normal ALT and undetectable viral load. Should I stop before I develop resistance?
- This is a tough call. Probably would not change right now – wait to see what happens.
- Make sure your DNA test is the most sensitive it can be. Stay on lamivudine, but if resistance develops, then try another oral antiviral drug.
What is the future for combination treatment – first using an antiviral to decrease viral load and then starting interferon?
- Combination is the future of treatment, but safety of the drugs right now is an issue, so we are left with sequential treatment. Right now combination of lamivudine and adefovir may be useful.
What about CT scans vs. ultrasounds and MRI for liver cancer (HCC) screening?
- CT scans and MRI are reserved for those who have cirrhosis. A European study showed that ultrasounds can miss 1/2 of all liver cancers and MRIs can miss 1/3 of cancers. In a non-cirrhotic liver, it is easier to see a lesion via ultrasounds (it is more difficult with a cirrhotic liver). There are cirrhotic livers, however, that look normal on ultrasound, but you can still miss a tumor. For example, you can have a “normal” ultrasound, CT scan, and MRI, but a liver biopsy can reveal cirrhosis. There is still controversy as to which imaging technique is better.
- If you use CT, you need intravenous (IV) contrast in order to see a new hypervascular lesion, or you might miss the tumor. We use a triple-phase CT, which is the best way to pick up a tumor. Having a normal ultrasound, CT scan, or MRI, does not rule-out cirrhosis (only a liver biopsy can accurately rule out cirrhosis). Once a patient has cirrhosis, ultrasound is not adequate for screening.
Should I be concerned about the higher radiation risk from a CT scan? Since it has 20 times more radiation than an X-ray, is a CT scan twice a year dangerous?
- Yes, you should be concerned. Although MRIs are more expensive, they are preferable because there is less radiation. But some patients do not want MRI because it can cause feelings of claustrophobia. Some doctors feel that CT scans are better for liver cancer screening.
What is the prognosis of liver cancer (or HCC) due to chronic HBV?
- Liver cancer, if found early, can be cured. Transplantation is preferable to resection. The success of transplanting cancer patients is just as good as those without cancer. Radio Frequency Ablation (RFA) slows down the liver cancer, but does not cure it. However, RFA can be useful while waiting for a liver transplant.
- We need to find better treatments so that people don’t end up with HCC. Outside the U.S., people cannot get a liver transplant due to lack of money, access and resources. The goal is to make HBV treatments accessible to the world so that patients don’t get liver cancer.
If you are treating a young patient who has never been on treatment, what antiviral would you use first?
- Every doctor will give you a different answer depending on their experience and preference.
- Would probably shy away from lamivudine. Might use a combination such as adefovir and lamivudine.
- Lamivudine resistance predisposes you to entecavir resistance, so by starting with it, you might be excluding yourself from two drugs. That is, if you develop resistance to lamivudine, your only option is adefovir since entecavir is not effective against lamivudine resistant virus. Currently, there are only 3 approved oral antivirals – lamivudine, adefovir and entecavir.
What is the goal of treatment, if you are already e-antigen negative?
- The goal is to achieve a lower viral load, normal liver enzymes, and a better histology on liver biopsy. The tough decision is to know when to stop treatment.
How do you talk to your doctor when you disagree and are well informed about management and treatment issues?
- Be polite! Ask questions such as, “Have you heard about this….”, or “Would you consider using a CT scan instead of an ultrasound for liver cancer screening?” Start with open-ended questions to encourage conversation rather than confrontation.
- Tell your doctor about this patient conference and all the information you learned at the HBF. Offer to share this new information and literature. Tell them you belong to an online support group where you learn a lot. If you have an unreasonable person, then there is not much you can do but find another doctor. But most will be reasonable if approached with courtesy and sincerity.
This summary is being made available as a courtesy only; therefore, please be sure to speak with your health care provider (or attorney if filing a disability claim) if you have any questions about the information in these notes.