• Hepatitis B
• Treatment
• Prevention

The Hepatitis B virus

This is a virus that multiplies in the liver and can cause liver damage.

• One third of the world’s population have past or present infection with the Hepatitis B virus.
  • There are 350 million with chronic Hepatitis B infection in the world.
  • There are probably over 90,000 people in New Zealand with chronic infection.
    • Only 30,000 have been identified - the rest do not know they have the infection.
    • The National screening program attempted to find these people with chronic infection and was only partially successful.
  • The rate of carriage of Hepatitis B is 6-8% for Maori, Pacific Islander and Asian populations but less than 1% for Europeans.
    • There are very high rates of chronic infection in some Pacific Island groups (e.g 13% in Tongans).
      
• Hepatitis B virus is spread through blood and other body fluids (including saliva). The infection can be caught by:
  • Most commonly the infection is acquired at birth or in early childhood.
    • Mother to child passage (at childbirth).
    • Close contact of children in early childhood.
  • Less common and relevant to adult infection are sexual contact, sharing of needles, tattooing equipment, sharing personal items (razors, toothbrushes), needle-stick injuries (health care workers).

Outcomes of the infection

• There are a wide range of outcomes of the infection depending to a large extent on the age at which the infection is acquired.
  • Overall most people who are exposed to Hepatitis B will become immune.
    • This means the virus has been cleared.
    • There are no problems with health in the longer term.
  • Infection acquired as an adult.
    • This is more likely to lead to a “hepatitis” illness with jaundice.
    • The majority of people with adult infection become immune.
  • Infection as a newborn (at delivery) or in the first 5 years of life.
    • High chance of developing chronic (long-term) infection.
    • Most infections are “silent” - not picked up at the time because there were few symptoms.
    • Men have a higher chance of developing chronic infection.
      
• If chronic (persistent/ ongoing) infection develops there are two main outcomes.
  • Inactive infection.
    • This can be called a “carrier” state.
    • The virus is relatively dormant.
    • Liver tests stay normal throughout life.
    • There are minimal risks of liver disease over a lifetime.
  • Active infection.
    • There is "active" turnover and multiplication of the virus.
    • There is inflammation in the liver and the potential for liver damage.
    • The body’s immune system is trying to kill the virus (without success).
    • In the process the immune system is causing liver cells to die.
    • This usually means having the Hepatitis B 'e' antigen.
    • Some people over time develop a mutant form of the virus that does not express the 'e' antigen.
  • For a young adult (less than 30 years) with active disease there is a reasonable chance that the immune system with be able to get on top of the infection.
    • This is called seroconversion because a protective antibody is formed.
    • Unfortunately it is more common that the infection continues to be active and there is slow but progressive damage to the liver.
      
• The long-term risk is the development of cirrhosis (scarring of the liver) and the risk of developing liver cancer.
  • The risk is 20% over 20 years for active infection.  In NZ there are about 10 liver transplants performed per year for hepatitis B.  In NZ there are over 200 liver related deaths per year from hepatitis B.

Diagnosis

• The presence of the virus in the liver is determined by the Hepatitis B surface antigen test.
  
• Active "turnover" (replication) of the virus is detected by;
  • Having the Hepatitis B e antigen.
  • Or by having high levels of virus DNA in the blood.
    
• The degree of the inflammation in the liver.
  • Can be determined to some extent by the liver blood tests (liver enzymes ALT and AST) but a liver biopsy is the most accurate assessment.

Goals of therapy in chronic hepatitis B

• The main goals of treatment:
  • Completely getting rid of the virus from the body is rarely possible therefore converting the infection to an "inactive" state is the main goal.
  • This is measured by loss of e antigen or the  absence of Hepatitis B DNA in the blood.
  • Liver enzyme tests should return to normal - this suggests that liver inflammation had subsided.
  • Improvement in symptoms is actually not a main goal as the infection often causes no symptoms until there is advanced liver disease.
  • Prevention of progression of liver disease and prevention of liver cancer.  This is hard to prove for any particular treatment but it seems that any treatment that leads to normal liver tests for a significant period of time reduces the risk of serious complications.

Treatment

• Lamivudine (Zeffix)

  • The most commonly prescribed treatment is lamivudine (Zeffix).
    • It works by inhibiting an enzyme in the virus essential for replication (HBV reverse transcriptase).
  • Lamivudine is very effective at inhibiting replication (formation of new viruses).
    • Hepatitis B virus is usually undetectable in the blood after 4 weeks of treatment.
    • However there is a low rate of seroconversion - that is the formation of effective antibody against the infection.
    • Only 10% of people will have antibody (to the “e” antigen) after 1 year of treatment.
    • About 30% will have antibody after 3 years of treatment.
    • If antibody forms it usually possible to stop treatment without relapse of infection.
  • For most people treatment needs to be long-term to continue to suppress the virus.
  • The main problem with long-term treatment is lamivudine resistance.
    • When this occurs there is breakthrough and new viruses are made again.
    • The rate of replication (formation of new viruses) usually increases when lamivudine resistance occurs.
    • The chance getting a resistant virus is about 10% after 1 year, up to 50% after 3 years and maybe 70% at 5 years.
    • Resistance is detected by a rise in levels of the virus in the blood (HBV DNA) and by a rise in liver enzymes (ALT, AST).
    • This means that these tests should be performed on a regular basis (every 3 months).
    • The main approach to resistance is to add another anti-viral drug - currently this is adefovir (see below).
      

• Interferon.

  • Interferon is another option. It works by enhancing the body’s immune response.
    • Seroconversion is usually preceded by “flare” in hepatitis.
    • The rate of seroconversion is approx. 30-40%.
    • It works better if there are higher levels of activity in the liver (judged by liver enzymes and liver biopsy).
  • This has been given as 10 million units three times per week by subcutaneous injection (similar to a diabetic giving insulin) for 4-6 months.
  • Recent studies have shown that pegylated interferon is better tolerated and more effective.
    • This is a once per week injection.
    • Pegylated interferon is not funded for Hepatitis B in NZ at this stage.
    • To date this has not been taken up (in large numbers) around the world - i.e there is a preference for tablet treatment.
      

• Adefovir (Hepsera).

  • Adefovir has recently become available in NZ.
    • It is added to the treatment when there is lamivudine resistance.
    • Resistance needs to be proven by special tests looking for mutations of the virus.
    • Several studies suggest that the outcome is better if adefovir is started as early as possible (once resistance has occured).
    • The dose is one 10mg tablet daily.
    • The medication is generally well tolerated but can cause nausea, weakness, headache, diarrhoea.
    • Close follow-up is required with the first few months of treatment.
    • Adefovir will need to be continued for a long period of time.
    • Most experts do not advocate stopping the lamivudine, however at this time funding for both drugs is only possible if there is severe liver disease (cirrhosis).
    • If liver biopsy was not performed prior to starting lamividine this may be considered prior to starting adevofir.

• Entecavir is now available in NZ
  
  

•  It is a very powerful drug against hepatitis B and has less problems with resistance.  There is a problem with cross-over of resistance.  Previous treatment with lamivudine makes the drug less effctive
• Tenofovir and emtricitabine are drugs that are already approved for use against HIV and also appear to be powerful drugs against Hepatitis B.  Clinical trials are in progress.
  
• Combination treatments may become standard but more studies are required. 
  • Not all combinations will be useful.
  • For example lamividine and interferon is not better than interferon alone or lamivudine alone.
• Special situations that require treatment.
  • People who have "inactive infection" can =have the virus activated if they take treatment for cancer (chemotherapy) or medication that lowers the immune response (immunosuppressants).

Prevention of health problems from Hepatitis B

• Immunization in childhood is a very effective strategy for prevention and will eventually have a major impact on reducing the problems with Hepatitis B in New Zealand.
  
• Vaccination is recommended for people who may be at a higher risk of being in contact with the virus.
  • People who share a house with someone who has hepatitis B.
  • Sexual partners.
  • People on dialysis.
  • People who receive blood products for clotting problems.
  • People with any form of chronic liver disease.
  • Health care workers, emergency services, dentists etc.
    
• For a pregnant women with hepatitis B special care is required to prevent the virus being passed to the baby.
  • An injection of Hepatitis B immunoglobulin is given to the baby on the day it is born.
  
  
• The other major strategy for prevention has been a screening program to look for carriers of Hepatitis B.
  
• Identifying all the carriers in NZ would have many positive effects.
  • Family members can have tests and immunizations if necessary.
  • There is a heightened awareness and understanding of Hepatitis B in a family and hopefully all the children in the future will receive the vaccine.
  • A carrier once identified can have regular blood checks.
    • If there are elevated liver enzymes then specialist advice is required.
    • There may need to be treatment as outlined above.
  • Someone who has cirrhosis or advanced Hepatitis B will benefit from regular checks to pick up liver cancer at an early stage.
    • This is commonly done using a test called alpha fetoprotein – usually on a yearly basis.
    • Any elevation of this test should be checked with a liver ultrasound scan.

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