• Hepatitis C
• Diagnosis
• Long-term risks
• Treatment
• Liver biopsy

Hepatitis C

Worldwide 300 million people are infected with Hepatitis C.

In NZ population 0.45% of the population is positive for Hepatitis C antibodies

• The infection affects ethnic groups in NZ in equal proportions (in contrast to Hepatitis B). Hepatitis C is usually acquired without any symptoms (no hepatitis illness). A "carrier state" does not exist (in contrast to Hepatitis B)
  
• >75% have a history of intravenous drug use.
  • This may be only 1-2 episodes of use at a teenage party.
• 5%  have a history of blood transfusion prior to 1992 (before routine testing of blood was commenced).
• 5-10% have other risk factors.
  • Unsterile tattooing.
  • There are high rates in prison inmates (presumably related to i.v drug use).
  • Migrants from countries with high rates due to re-using unsterilised needles - e.g Egypt.
• 5-10% have no identifiable risk factors.

Lifestyle Issues

1. If you are considering treatment you will need to prepare for the possible impact on your lifestyle and relationships.
   
2. You could also require time off work to deal with side effects and/or need to arrange a flexible work schedule with your employer.
3. Personal relationships may come under pressure from mood altering side effects and disruptions to routine. A big part of preparing for treatment is preparing those who will support you so they can help you through this time.

Treatment (covered in separate section)

What if the treatment fails?

• It is likely that the liver inflammation will return at some stage if the virus is not completely cleared.
  
• Further treatment may be possible.
  • This depends on whether there was some initial response to treatment and on what sort of treatment was given. In general if treatment was given 5 years ago - then the newer types of treatment may be worth trying.
    
• Treatment has advanced rapidly over the last 10-15 years and it is likely that new treatments will become available.
  
• There does seem to be some benefit from treatment even if the virus has not been cleared. The risk of liver cancer appears to be decreased.

What about alternative treatments?

• There is much interest in alternative treatments such as homeopathy, herbal medicine, dietary changes, and various therapies to decrease stress. Overall the results are disappointing.
  
• It is important to be open and frank with your GP or specialist so that appropriate decisions are made.
  
• Some people with hepatitis C have very mild disease and do not need to consider medical treatment. In this situation a more holistic approach may be acceptable.
  
• The best “alternative” treatment is to:
  • Stop alcohol.
  • Lose weight.
  • Have a balanced diet (low fat, fresh fruit and vegetables).
  • However there is minimal evidence to support any other sort of dietary restriction and no evidence for any herbal treatment.
    
• Fatty liver is has a negative influence on the outcome of Hepatitis C.  Therefore weight loss, a low fat diet and regular exercise and minimal or nil alcohol intake are all helpful measures in a more holistic approach probably because of a reduction in the degree of fatty liver.


• What about a liver biopsy?
  • Liver function tests measure specific enzymes in your blood. Unfortunately, these tests do not accurately reflect the extent of inflammatory change and/or damage to the liver that can result from HCV infection.
  • Liver damage may be present even when these tests are normal.
  • There is little correlation between the severity of the symptoms and the extent of liver damage.
  • Therefore the only way to determine whether there is any damage to the liver is to physically examine a small section under a microscope (liver biopsy) although a new scanning technique called a Fibroscan may be helpful and decrease the need for liver biopsy.
  • Treatment can proceed without a biopsy - and indeed is unchanged reagrdless of the degree of fibrosis, but there may be some uncertainty about te severity of te underlying disease
    

  Useful links

1. New Zealand Hepatitis C support group www.hepc.org.nz
2. Hepatitis C Council of NSW (factsheets and FAQ are excellent) www.hepatitisc.org.au
3. American Liver Foundation< www.liverfoundation.org

How is the infection diagnosed?

• Most people have no symptoms although tiredness is common
  • Tests may be taken because of concerns about having a risk factor for infection.
  • Alternatively liver enzyme tests may have been done as part of routine blood tests and then subsequent tests reveal Hepatitis C.
    
• A few people present with the long-term complication of cirrhosis or liver cancer. They have had the virus for 30 years but have had no symptoms until serious problems have developed.


• Tests for the virus.
  • The Hepatitis C antibody test is a screening test.
    • The presence of Hepatitis C antibody does not suggest any immunity – it suggests the presence of the virus.
    • There are false positive results.
  • The confirmatory test is the Hepatitis C PCR.
    • This is a direct test for virus in the blood and is very accurate.
    • There are also false negatives for the antibody test.
    • If you have a risk factor then the PCR test is required to be sure that you do not have the virus.
  • More detailed tests of the virus are required before starting treatment.
    • There are subtypes (genotypes) – the results of this test will directly affect the duration of treatment.
    • In New Zealand the most common genotypes are 1a, 1b and 3.
    • There are also tests of the viral load – i.e how much virus is in the blood. 
      


• The Hepatitis C PCR test should be repeated during treatment to give some guide as to how effective the treatment has been to date.
  • It is usual now to have a viral load test at 3 months to assess how well the treatment is progressing.
  • An early test at 4 weeks is also helpful in predicting treatment response
    
  • If there is no response then it is better to stop at 3 months now as the success rate after completing all of the treatment will be very low (< 2%).

What is the risk of cirrhosis or liver cancer?

• The overall risk of developing cirrhosis is 1% per year.


• The risk is significant after 20 years of infection.
  • The date of infection may not be known but can be estimated if due to intravenous drug use.
  • The risk is higher is the virus is acquired later in life (for example from a blood transfusion at the age of 50 years).


• Alcohol intake significantly increases the risk of cirrhosis.


• If there is cirrhosis the risk of serious life-threatening complications is 5% per year and the risk of developing liver cancer is 3% per year.

General advice

• The risk of passing on the infection is very low.


• It is important to stop or least markedly decrease alcohol intake.


• Vaccinate against Hep A and B.


• Treatment cannot be started if still using intravenous drugs.
  • You must be stable on a methadone program for at least 6 months.
  What is the risk of sexual transmission of Hepatitis C?
  
  The likelihood that somebody with the virus could have passed it on to a sexual partner is worrying for many people. Should you tell past sexual partners of your Hepatitis C status? How should you discuss the topic with your current sexual partner? These are all are difficult issues to deal with.
  
  Hepatitis C is thought to be a blood borne virus that can only be passed on if the infected blood of one person gets into the bloodstream of another.
  
  Sexual transmission of hepatitis C is very uncommon. 
  

Current treatment for Hepatitis C

• Previous results from treatment were poor but there have been significant advances.
  • Treatment should only be started if life in general is stable and there are people to support you during treatment.
  • Treatment involves the need for regular weekly injections and 4-5 tablets per day.
  • It requires regular follow-up and careful following of instructions.


• Combination treatment is now the standard.
  • This is interferon combined with ribavirin (a tablet - an oral nucleoside analogue).
  • The duration of treatment is 6 – 12 months (depending on genotype / subtype of virus).
  • There are sustained response rates of 40 -70% (depending on the genotype).
  • Results are better for genotype 2 & 3.
    • About 50% in NZ are genotype 1.
    • People with this genotype require 12 months of combination treatment.


• Pegylated interferon.
  • This is given only once per week.
  • It is now available for all genotypes.
  • The switch from regular interferon to pegylated interferon has improved the success rates for all virus subtypes.

Side effects

• Interferon/ribavirin combination treatment may cause some side effects ranging from mild to very severe.
  • Side effects can vary considerably from person to person.
  • One person may experience several side effects intensely while another has few or only mild reactions.
    
• Common side effects include;
  • Flu-like symptoms such as lethargy, headache, muscle aches, joint aches and fever/chills.
  • Loss of appetite, nausea, mouth ulcers.
  • Increased irritability mood swings, insomnia, fatigue, depression.
    • These symptoms can be significantly improved with anti-depressant medication.
    • The treatment lowers serotonin levels in the brain causing depression i.e a chemical change directly related to the medication.
    • This can be restored to normal by a drug such as Citalopram.
  • Hair loss.
    
• Lowering of blood counts, especially white blood cells and platelets is more common with pegylated interferon. Usually treatment can be continued but may require a lower dose.


• Exacerbation of "auto-immune" disorders.
  • Thyroid abnormalities are generally not serious and are reversible once treatment is stopped.
  • Psoriasis may be worsened.
    
• Ribavirin.
  • Animal studies have shown that ribavirin can cause birth defects.
    • Men and women undertaking combination therapy are required to practise effective birth control during treatment and for six months afterwards.
  • Ribavirin has also been associated with anaemia (low red blood cell count).
    • This is carefully monitored during treatment and doses are adjusted to suit.
    • It is a particluar problem for those with underlying heart or lung disease.

• A liver biopsy is a simple outpatient procedure (usually with a ultrasound scan to help determine the area to biopsy).
  • There are some risks of a liver biopsy.
  • Some discomfort at the time of the biopsy is common.
  • About 1% of patients experience significant bleeding which may cause abdominal pain and lowered blood pressure. Hospital admission is required sometimes (perhaps 1:250).
  • There have been deaths as the result of a liver biopsy. The exact risk is hard to determine because this is so uncommon.  A fair assessment of risk would be 1 in 3000.
  • Therefore liver biopsies are not recommended lightly. The risk of bleeding is partly assessed by clotting tests but the risk cannot be completely eliminated.



• Liver biopsy in hepatitis C.

  • Not every person with HCV infection may require - or indeed, want - a liver biopsy.
  • The decision as to whether you have one will be a joint decision involving your specialist and yourself.


• A liver biopsy can be considered if the liver enzymes are normal because it is still possible to have significant liver disease.
  • The biopsy will give an assessment of inflammation and scarring.
  • Inflammation is reversible but scarring is not.
  • Those with mild inflammation after 20 years may never develop serious liver disease. In this situation no treatment or deferred treatment is a reasonable option.
  • Those people with moderate to severe inflammation have a higher risk of developing scarring over time.
    • This may help with planning of treatment.
    • The knowledge that there is significant liver disease may help motivation if there are problems with side-effects from the treatment or if repeat treatment is being considered.
  • Fibrosis is the thickening and scarring of the connective tissue as a result of inflammation.
    • Excessive scarring can result in cirrhosis.
    • Cirrhosis is the irreversible hardening or scarring of fibrous scar tissue in the liver.
    • Cirrhosis affects the 'architecture' of the liver. This scar tissue compromises the blood flow through the liver and the function of liver cells.
    • People with cirrhosis tend to respond less favourably to interferon treatment.
  • More than a mild degree of scarring is a strong argument for starting treatment now rather than waiting.
  • There is now a new technique for diagnosing fibrosis or cirrhosis without a liver biopsy.  This is called a Fibroscan. It is hoped that some people will be able to avoid having a biopsy with this test