Treatment for Hep C
Combination Therapy
While research is ongoing, Western medicine currently provides a limited choice in terms of pharmaceutical treatment for people with hepatitis C. The standard treatment currently available is usually referred to as combination therapy, as it utilises a combination of two different kinds of drugs.
WHAT IS COMBINATION THERAPY?
In combination therapy, the drugs pegylated interferon and ribavirin are used together to help boost the body's own immune response to the hepatitis C virus. Interferon was approved for clinical trials in Australia in 1992 and became available under the Commonwealth subsidised Pharmaceutical Benefits Scheme in 1994. In November 2003, pegylated interferon - a slow release form of interferon also used in combination with ribavirin - was approved for listing with the PBS.
Pegylated interferon in combination with ribavirin has been shown to be significantly more effective than standard interferon and is now the preferred treatment for people with hepatitis C worldwide. Significant improvements in outcomes from treatment have meant that the possibility of achieving a sustained virological response (SVR) occurs in 45% to 90% of people with hepatitis C, depending on genotype. Pegylated interferon monotherapy is now considered if there is a known severe reaction to ribavirin.
Pharmaceutical treatment for hepatitis C will generally take either six or twelve months, depending on which genotype of the virus is being treated. The pegylated interferon is given under the skin, usually in the stomach area, once a week and ribavirin tablets are taken twice daily by mouth.
HOW DOES IT WORK?
Interferon is produced naturally in the body as part of the immune system's defence against infection. Synthetically manufactured forms of interferon are administered in large doses with the aims of boosting the immune response to hepatitis C, reducing the replication of the virus in the body and slowing down or stopping the disease process.
Ribavirin is a drug that alters the body's immune response to viruses although exactly how it works is unclear. It has been shown to work best on the hepatitis C virus in combination with interferon, and is not effective against hepatitis C infection as a treatment on its own.
WHAT IS THE RESPONSE RATE?
It is currently believed that a person's response to combination therapy is related to the following factors:
- Genotype (strain): Genotype 2 and 3 have been shown to have a response rate of around 80%, whereas genotypes 1 and 4 have a response rate of around 45%.
- Extent of liver damage: More advanced fibrosis (scarring of the liver) is associated with a lower response rate.
- Body mass index: A condition called 'fatty liver', usually associated with being overweight, can decrease the effectiveness of treatment.
- The level of virus in the blood (viral load): People who have low levels of virus in their blood before starting treatment are more likely to successfully clear the virus from their body.
Research has also demonstrated that people who drink alcohol during treatment have a reduced chance of successfully clearing the virus. It is recommended therefore that people abstain from drinking alcohol during treatment or at least restrict their alcohol intake to seven standard drinks per week or less (a standard drink contains 10g of alcohol).
The aim of treatment is to achieve a sustained virological response or SVR (that is, the virus is no longer detectable in the blood six months after finishing treatment). The eradictation of the virus leads to an improvement in symptoms and a reduction of potential long-term complications such as cirrhosis and liver cancer.
WHY DOES GENOTYPE MATTER?
If a person is considering treatment, it is important to find out which genotype he or she has, as this influences decisions about length of treatment and expectations of the person's response to treatment. Research indicates that the response rate to treatment is influenced by genotype. People with genotype 2 and 3 have the same response rates after either six or 12 months of treatment so six months is sufficient for most people with these genotypes, although those with significant liver scarring or those with high viral load may benefit from 12 months of treatment. Some investigators have tried to shorten treatment regimens for people with genotype 2 and 3; however, a recent large study had shown that 24 weeks treatment still provides the highest SVR rates.
Patients with genotype 1 achieve higher SVR rates following 12 months treatment rather than those treated for six months. Fewer people with genotypes 4, 5 and 6 have been studied in clinical trials and thus less in known about the best treatment regimens for them.
Genotypes can be determined using a PCR test (see the section on testing). If a person is about to undergo treatment or take part in a clinical trial, genotype testing is covered under Medicare. Testing requires a blood sample and can be done through a general practitioner or liver clinic. It takes about two weeks to get the results of a genotype test.
At this stage, there is little evidence of any correlation between genotype and severity of disease. Some studies have linked genotype 1b with severe liver disease. It is worth noting, however, that the people in these studies generally had hepatitis C for a long time and acquired the virus through blood transfusion during surgery for another ailment.
WHAT ARE THE SIDE EFFECTS OF TREATMENT?
Combination treatment can cause a range of side effects, which may vary in intensity for each person. Side effects can include: fatigue, fever, chills, muscle aches and headaches, irritability, mood swings and depression. Some people experience loss of appetite, insomnia, nausea, vomiting, diarrhoea, skin rash, hair thinning, eyesight problems and weight loss. Other side effects such as thyroid disorders may occur but are less common.
Ribavirin is tetragenic, which means that it is toxic to a developing foetus. Consequently, combination treatment is not made available to women who are pregnant and/or breastfeeding or thinking about becoming pregnant, or to men whose partner is pregnant or thinking of becoming pregnant. People undergoing treatment must agree to use two forms of contraception during, and for up to six months after treatment.
Ribavirin can also temporarily lower a person's red blood cell count (anaemia). This may cause tiredness, shortness of breath and a decrease in energy levels, and an adjustment of ribavirin doses may be required in some cases. Pegylated interferon may temporarily lower a person's white blood cell count, which can reduce the body's ability to deal effectively with infections and it may also cause low platelets which can impair the body's ability to clot blood. For these reasons, people undergoing treatment have regular blood tests to monitor possible side effects and adjust doses of both drugs, if necessary.
Source - Impact booklet, produced by Hepatitis C Victoria, June 2008