Hepatitis Treatment

A glossary of terms is provided to help you understand the words used here and by your doctor.

DISCLAIMER: Many factors influence the decision to treat an individual patient. Individuals should always discuss diagnosis and treatment options with their healthcare provider. We complied this information from a number of sources including government publications, peer reviewed medical journals, pharmaceutical documents, and expert opinions. We provide this information to help you to be informed about hepatitis treatment. We do not endorse any specific product. If you have questions or concerns about the information provided here- please contact HepTREC or your healthcare provider.

Last update 8-5-05

Hepatitis A Treatment

If you think you’ve been exposed to hepatitis A, contact a doctor or your local health department. You could help prevent the spread of hepatitis to other people.

Hepatitis A infection usually clears up on its own. It may take a few weeks. There is no specific treatment for hepatitis A. Some doctors may prescribe medications or actions that will help reduce the symptoms of the infection. Get lots of rest, drink water, and avoid alcohol or other chemicals that could harm the liver.

If you have chronic hepatitis B or C and are exposed to hepatitis A, call your doctor. The illness could be more serious in people with liver disease.

The best way to treat hepatitis A is to prevent it; consult a healthcare provider about vaccination against hepatitis A!

For more information about hepatitis A:
Visit the CDC website at http://www.cdc.gov/ncidod/diseases/hepatitis/a/

Hepatitis B Treatment

Today, there are a number of treatment options for Hepatitis B. These treatments were developed and improved in the past 10-15 years, so if in the past your doctor told you that there are no treatments for hepatitis B, ask again!

If you were infected recently (within the last 6 months) you may want to see if you get rid of the virus on your own before starting treatment.

Before treatment is started, it is important to make sure there is indeed a current hepatitis B infection. It sounds silly, but tests for Hepatitis B are often misinterpreted- even by doctors. Some blood tests will be positive if a person was vaccinated against Hepatitis B or was infected with Hepatitis B and recovered. Make sure the test for hepatitis B surface antigen (HBSg) is positive before you consider taking hepatitis B treatment.

Not all cases of hepatitis B need to be treated and treatment usually doesn’t need to be started right away. Your doctor may want to do a liver biopsy before deciding about treatment. The biopsy will allow the doctor to see if liver scarring or fibrosis is present.

There are pluses and minuses for each treatment so take some time to learn about the treatments and discuss the details with a doctor experienced in treating Hepatitis B.

The treatments help reduce the amount of virus in the body - which reduces damage to the liver. The less damage to the liver, the better the liver can function. Preventing more damage and improving the health of the liver is the goal of the current hepatitis B treatments.

There are a few treatment options: interferon and anti-viral medications.

Interferon is a protein that the body produces in very small amounts to help fight off infections. Interferon is also manufactured and available as a medication to treat health conditions including Hepatitis B and Hepatitis C. Interferon for Hepatitis B is currently prescribed in two forms : Interferon-alpha and pegylated interferon. Interferon-alpha is currently sold under the names of Intron A, Infergen, and Roferon. Interferon-alpha is injected under the skin daily or a few times a week. Pegylated interferon is currently sold with the names Pegasys and PegIntron. It is injected once a week. Pegasys was recently approved by the FDA for hepatitis B treatment.

There are side effects to interferon treatment, but there appears to be no risk of viral mutations. Side effects usually include flu-like symptoms (fatigue, headache, bodyaches), depression, and headaches. Many of these side effects can be managed by drinking more water, getting more exercise, sleep, and eating a balanced diet. Medications can also help relieve the side effects. If you have side effects, you should talk with your doctor about ways to eliminate or manage them.

Lamivudine (sometimes called 3TC) is a pill or oral solution that is taken everyday for about 1 year, though sometimes longer. It is currently sold under the names of Epivir-HBV, Heptodin, and Zeffix. Lamivudine directly attacks the virus makes it hard for it to replicate. This medication has been used at higher doses for years to treat HIV.

There are few side effects from this medication, but the virus can mutate and become resistant to the medication and possibly harder to control. Sometimes hepatitis gets worse when treatment is stopped. It is important to be very compliant with the treatment. Treatment with a combination of interferon and lamivudine is being studied.

Adefovir dipivoxil (HEPSERA) is a pill that is taken once a day for a year or more. Like lamivudine, it interferes with the viruses ability to replicate. Adefovir appears to produce fewer mutant viruses than lamivudine, though long-term studies are still under way. Like lamivudine, hepatitis can get worse when treatment is stopped. Some people who developed mutants on lamivudine are prescribed Adefovir.

It is very important to be compliant and take the medication as prescribed. This will help you reduce the amount of virus in the body and reduce the likelihood of mutant formation.

Entecavir is another antiviral medication that is available as a pill or oral solution. It was very recently approved by the FDA and is currently sold under the name Baraclude. The medication is taken every day for a year or more. Like the other antiviral medications, it is possible for hepatitis to get worse after treatment is stopped.

Talk with your doctor about length of treatment and medication doses. While there are standard recommendations, each patient’s circumstance is different.

The Future of Hepatitis B Treatment

References for hepatitis treatments mentioned above:

• Treatment Alternatives for Chronic Hepatitis B Virus Infection: A Cost-Effectiveness Analysis Annals of Internal Medicine 2005 142: 821-831.
• Hepatitis_b_guidelines.pdf
• A Randomized, Controlled Trial of Combination Therapy for Chronic Hepatitis B: Comparing Pegylated Interferon - 2b and Lamivudine with Lamivudine Alone. Annals of Internal Medicine (volume 142, pages 240-250
• www.fda.gov/bbs/topics/ANSWERS/2005/ANS01348.html

Hepatitis C Treatment

Hepatitis C treatment has improved substantially during the past few years. The treatments today are easier to manage and more effective than just a few years ago. If your doctor told you in the past that there are no treatments for hepatitis C, ask again!

Before treatment is started it is important to make sure there is indeed a current hepatitis C infection. Some people do recover from hepatitis C infection on their own, so make sure that both the antibody screening test is positive and virus is detected before treatment is started.

Who should receive treatment

If you were recently infected with hepatitis C, your doctor may want to wait to see if you fight off the virus on your own before starting treatment.

Not all people need to be treated for hepatitis C and some health conditions like heart disease or psychiatric conditions may be affected by the treatment. Doctors will consider a number of things before prescribing treatment such as:

• Fibrosis or nodule formation in their liver biopsy. Patients with these conditions usually progress to cirrhosis. Elevated liver enzymes (ALT and AST)
• Other health conditions
• Detectable hepatitis C virus (remember that any amount of detectable virus means a person is infected)
• Ability to follow the treatment plan

Some people and doctors consider waiting until the hepatitis “gets worse” before starting treatment. It is important to note that the more fibrosis in the liver, the less effective the treatment. So, waiting until there is significant fibrosis in the liver reduces the chances of a positive response to the therapy.

Interferon and ribavirin:

Interferon has been used for years to treat hepatitis. The treatments have improved over the years. Initially, interferon-alpha was taken by itself and injected 3 times per week. Interferon taken alone is called interferon monotherapy. Interferon monotherapy was improved by the addition of ribavirin. Ribavirin improved the effectiveness of the interferon therapy.

The next improvement to therapy was the introduction of pegylated interferon. Pegylation is the addition of a molecule to the interferon to extend it’s survival in the body. Pegylated interferon is injected once a week and the level of interferon in the blood fluctuates less. Use of pegylated interferon alone is monotherapy. Pegylated interferon is also used in combination with ribavirin. The effectiveness of pegylated interferon is improved with the addition of ribavirin.

Trade names for interferon include Intron A, Infergen, and Roferon. Two pegylated interferons are approved for hepatitis C treatment. PegIntron is pegylated Intron A. Pegasys is pegylated Roferon.

Trade names for ribavirin include Rebetol and Copegus. Generic ribavirin is also available.

Length of treatment

The recommended length and dose of treatment varies by genotype of the virus, treatment history, weight, and in some cases amount of damage to the liver.

In general, recommended length of treatment for genotype 2 and 3 is 24 weeks. The general recommended length of treatment for genotype 1 and 4 is 48 weeks. If a patient was treated with interferon and ribavirin in the past and relapsed, doctors will sometimes retreat the patient and continue for a longer period of time. It is important to stay on treatment for the recommended time period and not stop if the virus is undetectable! Compliance with recommended therapy is the best chance for success.

Dose of medication varies by the product used and sometimes the weight of the patient and treatment history. Some may want to reduce the dose of their medication if side effects appear. It is important to discuss and try side effects prevention or management rather than reduce the treatment dose. Getting a second opinion about side effects management or joining a support group can often help.

How well does the treatment work

Response to therapy is measured by reduction in the level of hepatitis C virus in the blood. Patients respond differently therapy. It is hard to predict how any one individual will respond to the therapy at the start, but your doctor will follow your response by checking your viral load periodically through treatment.

Most patients will experience a reduction in viral load. A couple of factors influence how well the treatment works. These factors include the virus genotype (patients with genotypes 2 and 3 generally respond better than those with genotypes 1 and 4), how well a patients complies with the treatment, and the extent of fibrosis or scarring in the liver.

Treatment response is typically measured at 12 weeks, 24 weeks, at the end of therapy, and at 6 months after treatment.

• Early Viral Response (EVR): This is the response measured at 12 and/or 24 weeks. Most people who will go on to clear the virus will see a significant drop in the level of virus in the blood at this point. Doctors and insurance companies typically expect to see at least a 2-log drop in viral load (this means for example, from 2 million iu/ml to 20,000iu/ml). Sometimes the virus has dropped enough to be undetectable. It is possible for people who do not see this drop to go on and clear the virus, but it is not common. Some insurance companies are cutting off payment for treatment if the 2 log drop is not achieved. Do all you can to take all the medication all the time to increase your chance of an EVR! Talk with your doctor about ways to reduce side effects without reducing the dose of medication. Make sure you have all your pharmacy and lab issues addressed before starting treatment. You don’t want to miss doses because you don’t have the medication on hand! If you do not see an EVR, talk with your doctor about the continuation of treatment.
• End of Treatment Response (ETR): This is the response measure at the end of treatment. Ideally, the virus will be undetectable at this point. If it is not, your doctor may recommend continuing treatment for an additional period of time. You should discuss pros and cons with your doctor. Remember that even if you still have some detectable virus, the treatment will have helped your liver fight off the virus and that your liver is likely is healthier than before.
• Sustained Viral Response (SVR): This is the response measured 6 months after completion of treatment. If the virus is undetectable at this point, it is called sustained viral response. Most, about 95%, of people who achieve SVR stay that way. Some doctors say the SVR patient is “cured”. Other people do not use that term, for they fear the virus may still be there but at very low levels that can’t be measured. At this point we know that those who achieve SVR, do not appear to have any additional damage to the liver!
• Relapse: The virus becomes undetectable during treatment but comes back once treatment stops. Some believe that the virus may remain in some liver cells during treatment and when treatment is stopped, the virus starts to replicate again. Patients who relapse should discuss other treatment protocols (including increasing dosage or length of treatment) with their doctor.
• Nonresponse: Virus is detectable during and after treatment. Patient who do not respond to the therapy should talk with their doctor about altering treatment protocols. Some patients who do not respond have had difficulty taking all their medication due to side effects or life events. These patients may respond if all the medication on time for the entire time. Others just do not respond to treatment even if they are very compliant. These patients should discuss options with their doctor. Some doctors will suggest waiting for new treatments, others may suggest changing the treatment protocol, others still may recommend that the patient continue to take interferon at a low dose for a long period of time. This “maintenance therapy is believed to help prevent liver damage.

What is the expected level of response? Medical treatments have improved greatly in the past few years, and the percentage of patients who are Sustained Viral Responders has also increased. The data below is compiled from a number of sources. It is not possible to predict how any one patient will respond until treatment has started. There are factors that influence success of treatment (see influences section below).

• When interferon-alpha is used alone, about 15% of patients will achieve SVR.
• When pegylated interferon is used alone about 30% of patients will achieve SVR.
• Combination therapy (interferon-alpha and ribavirin) raises the SVR percentage to about 40%.
• Combination therapy (pegylated interferon and ribavirin) increases the SVR percentage to over 50%.
• More than 95% of patients who achieve SVR have no evidence of the virus 5 years after treatment.

What influences treatment success ? Some things improve the chance of responding to therapy:

Genotype of virus. Genotypes 2 and 3 may require only 6 months of treatment and the likelihood of achieving SVR are about 80%!!

Baseline Viral Load. Starting treatment with a viral load of 800,000 iu/ml or higher is less favorable.

Race. For reasons that are not understood, African Americans do not respond to treatment as well.

Obesity. Obese patients do not respond as well to treatment as those who are not obese.

Cirrhosis. Patients who have cirrhosis or advanced fibrosis do not respond as well to treatment.

It is impossible to change most of these factors. You can’t change your viral genotype or race, for instance. But ,if you are very overweight, you might lose weight before starting treatment to improve your chances of responding.

The liver can benefit from treatment even if the virus is not eliminated. Sometimes doctors stop treatment if they don’t see the virus go away. Consider discussing the benefits of continued treatment with your doctor.

Treatment side effects

Many patients experience side effects from the two medications used to treat hepatitis C. The side effects can range from slight discomfort, to inconvenience, or disability. Most of the side effects can be prevented or managed, so don’t let fear of side effects interfere with treatment decisions.

Interferon side effects

Some side effects from interferon show up soon after treatment is started (early side effects) other appear later in the course of treatment or stay with the patient during treatment (persisting side effects).

Early Side Effects

• Flu-like (Inflammatory) symptoms
• Fever
• Chills
• Body Aches
• Headache
• Nausea
• Treatment – Anti-Inflammatory Medications
• Ibuprofen
• Naproxyn sodium (12-hour anti-inflammatory)

TIP:When you begin taking interferon take the anti-inflammatory medications for the flu-like symptoms BEFORE flu-like symptoms appear. It will be more helpful in reducing symptoms. Think of a snowball rolling down a hill – it’s much easier to stop at the top of the hill than halfway down.

• Fluids – Dehydration can make flu-like symptoms worse. Adequate hydration can help reduce side effects.
• Drink enough water to keep your urine a very pale yellow
• Stop drinking a couple of hours before bedtime to reduce the need for nighttime bathroom visits
• Caffeine is a diuretic (pulls fluids from the body), so avoid or limit caffeine while on interferon therapy

TIP: Morning headaches can be relieved by drinking a large glass of juice or water.

Persisting Side Effects

The side effects that appear later in interferon use can be difficult to deal with. They usually begin a couple of weeks or several months into treatment. The side effects are usually not severe enough to stop therapy and these side effects can be relieved with use of other medications. Talk with a doctor about the side effects and try not to reduce or stop therapy.

• Neutropenia (suppression of neutrophils, a type of white blood cell)
• Neutrophils fight infection
• Dealing with neutropenia – a medication called Neupogen can help reduce neutropenia.
• Treatment is considered when neutrophil count falls below 750,000 per ml (some may wait until count goes below 500,000)
• Neupogen is usually taken once per week
• Most effective when used a day or two before interferon injection
• Some physicians may choose to reduce the dose of interferon to stop suppression of neutrophils. However, this can reduce the effectiveness of interferon therapy, so patients should discuss the use of Neupogen with their doctors.

• Psychiatric Side Effects
• Depression – interferon therapy can cause true depression as well as these depression-related symptoms like
• Insomnia
• Short-tempered/irritability
• Fatigue
• Crying episodes
• Loss of appetite

• Treatment of depression-- Antidepressants
  Doctors and nurses may suggest taking an antidepressant if symptoms appear. Some even suggest that you take antidepressants BEFORE interferon therapy is started since it takes a few weeks for antidepressants to become effective. Sometimes depression gets worse as treatment continues. Increasing the dose of antidepressants can help. Consulting a psychologist can also help.
• If serious depression occurs, intervention of a psychiatrist is helpful. The doctors can work together so that hepatitis therapy can continue.
• Although rare, more serious psychiatric conditions occur, such as severe, suicidal depression. In this case immediate psychiatric intervention is needed, and interferon should be stopped.

• Other side effects

A few other side effects may occur. While unpleasant, they usually are not dangerous and gradually return to normal after therapy stops. They include:

• thinning hair,
• change in hair texture
• weight loss

Ribavirin side effects

• May cause birth defects
• Women who may become pregnant must use reliable birth control.
• Pregnant women may not take ribavirin.
• Women should not become pregnant for six months following the end of ribavirin therapy.
• If a woman is pregnant and her male partner uses ribavirin she should make sure he uses a condom with every act of intercourse – ribavirin is found in seminal fluid.
• Anemia
• Can be treated with medication called erythropoietin. Names for erythropoietin are Epogen and Procrit.
• Most patients see some improvement after two doses, but it takes several weeks before the full effect is felt.
• Some physicians may reduce the amount of ribavirin; this can reduce the effectiveness of treatment so consider use of erythropoietin.
• Nausea
• Take ribavirin with food to reduce this side effect
• Rashes
• Physicians may suggest skin creams or antihistamine
• A dermatologist can be consulted
• Allergy – ribavirin treatment must be stopped.  

Please discuss all side effect concerns with a doctor.

Nonresponders and Relapsers

For those who have taken treatment for hepatitis C and have not achieved an SVR, there are new approaches to therapy. There are no “breakthrough” treatments available, but many doctors are trying techniques to improve response. This could be retreating again for a longer period of time for people who relapse. For some people who are nonresponders, a different type of interferon called consensus interferon is sometimes used with ribavirin. This interferon is not available pegylated, so patients who take this interferon (also called Infergen) must have an interferon injection every single day. Studies are underway to see how well this treatment works, focusing on the patients who are the most difficult to treat. These are usually people with genotype 1, have a high viral load, and many times are African American. Many of these patients have cirrhosis or advanced fibrosis. If you are a nonresponder to pegylated interferon and ribavirin, talk to your doctor about whether you might benefit from Infergen. If you or your doctor want references for this treatment please contact HepTREC at info@heptrec.org.

Maintenance Therapy

Nonresponders with cirrhosis might benefit from maintenance treatment. This consists of pegylated interferon at a lower dose than usual (half or one-third) without ribavirin. Doctors think that interferon can help “cool down” inflammation in the liver and might prevent liver failure and liver cancer. This approach is currently being studied in three large nationwide trials. Talk to your doctor if you are a nonresponder, or have cirrhosis. In some cases people with advanced cirrhosis who are not able to take full-dose pegylated interferon and ribavirin might be able to take lower dose peginterferon. If your doctor is not familiar with this treatment, check into the studies. If you or your doctor want references for this treatment please contact HepTREC at info@heptrec.org.

Future Treatments for Hepatitis C

Many organizations are working to develop better treatments for hepatitis C. Most work toward supplementing or modifying existing treatments; some are testing drugs that were developed for other conditions to be used against HCV.

You can monitor clinical trial activity for HCV at www.centerwatch.com and the HCV Advocate web page

http://www.hcvadvocate.org/community/trials.asp

References for hepatitis C treatment  

http://consensus.nih.gov/cons/116/116cdc_intro.htm  

http://www.fda.gov/fdac/features/1999/299_hepc.html