Interferon: Interferon is a substance naturally produced by the body to defend itself from infections, including the hepatitis C virus, and tumours.  The interferons used in treatment are synthetically manufactured and taken in much higher doses than would occur naturally in the body.  They work to boost the body’s normal defences against hepatitis C.  Interferon was the first proven treatment for hepatitis C, requiring three subcutaneous (under the skin) injections per week, and effective for only a small number of people.

Pegylated interferon: The addition of a large polyethylene glycol (PEG) molecule to interferon produces a molecule that lasts a lot longer in the body, meaning that only one injection per week is required.  This change has resulted in considerably fewer peaks and troughs in drug levels in the blood, greater tolerability and improved effectiveness in fighting the hepatitis C virus.

Ribavirin: Ribavirin is an antiviral drug which, when given in combination with interferon (including pegylated interferon), reduces the virus’ ability to reproduce.  The dosage of ribavirin is based on a person’s weight and is taken orally twice daily.  Some people may require a dosage adjustment during treatment.

CAUTION:  Ribavirin should not be used while pregnant, or planning on becoming pregnant, or by men whose female partners are pregnant or planning to become pregnant. It has been shown to cause serious birth defects and other problems in animal studies.  It is not known whether ribavirin passes into human breast milk. However, ribavirin does pass into the breast milk of animals and can cause problems in for them and their offspring.

Treatment Criteria: Subsidised pegylated interferon and ribavirin treatment is available to people who satisfy all of the following PBS S100 criteria:

• Blood tests: documented chronic hepatitis C infection (repeatedly anti-HCV positive and HCV RNA [PCR] positive);
• Age: must be 18 years or older;
• Contraception: female patients of child-bearing age are not pregnant, not breast-feeding and both patient and their partner are using effective forms of contraception (one for each partner).  Male patients and their partners are using effective forms of contraception (one for each partner).  Female partners of male patients are not pregnant. NB Ribavirin is a category X drug (causes birth defects) and must not be given to pregnant women.  Pregnancy in female patients or in the partners of male patients must be avoided during treatment and during the 6 month period after cessation of treatment.
• Treatment history: received no prior interferon or pegylated interferon treatment for hepatitis C.

Australian Government, Department of Health and Ageing

Schedule of Pharmaceutical Benefits for Approved Pharmacists and Medical Practitioners-Operative from 1 January 2007, p. 497

Liver biopsy

While a liver biopsy is no longer mandatory under the S100 criteria there are occasions when one may be required.  These occasions could include:

• Genotype 1 with high viral load
• Genotype 3 with suspected cirrhosis
• Co-infection with HIV or hepatitis B
• Suspected cirrhosis in longer term infection, regardless of genotype

What is a liver biopsy?

A liver biopsy is the removal of a tiny sliver of the liver using a fine needle.  This is then examined under a microscope for signs of disease.  It is a way to determine the condition of the liver.  Hepatitis C is a diffuse disease (the damage tends to be spread or distributed evenly throughout the liver) making the liver biopsy a very accurate means of assessing damage to the liver.

How is it done?

Informed consent must be given prior to a liver biopsy which is performed as a day case procedure.  Patients are required to fast (not eat or drink) before the procedure.  To guard against excessive bleeding, blood is taken to check platelet levels and clotting profile (preferably within a week of the liver biopsy). 

An ultrasound is usually performed beforehand so that the biopsy spot can be marked.  A local anaesthetic is injected into an area between the ribs on the right hand side.  The patient is asked to breathe in a particular way so that the doctor can locate the liver and its depth.  A small nick is then made in the skin to allow entry of the biopsy needle, which is quite fine – about 1.4mm in diameter.  The needle is inserted and a specimen of liver about 1 centimetre in length is taken.  A dressing is placed over the biopsy wound.

After the biopsy

Bed rest, either lying flat or on the right hand side, is required for 4 hours to prevent bleeding.  Pulse, blood pressure and the biopsy dressing are checked regularly.  Close observation is maintained for a further 2 hours, although the patient is allowed to get up and move around, and a light meal is usually provided during this period.  Some people may feel pain in the shoulder (referred pain) or discomfort in the abdominal region.  Medication for pain relief and nausea are provided where necessary. 

As is the case with many day procedures, the patient is not permitted to drive so must be collected and driven home AND must have someone stay with them overnight in case of any complications (see below).

Anyone who has undergone a liver biopsy is instructed to not do any heavy lifting or play contact or collision sports for a period of time following the liver biopsy.  Clinic staff will provide this information at the time of discharge.

Complications of liver biopsy

As with any invasive medical procedure, liver biopsy carries a degree of risk and, in rare cases, complications can occur (most commonly bleeding).  These risks should be discussed with patients prior to obtaining their informed consent to the biopsy.

It is vital that anyone experiencing severe pain, swelling in the abdomen, faintness or shortness of breath, or bleeding from the biopsy wound contact their doctor or the hospital immediately.

Treatment duration

Treatment duration is based on genotype and liver health.

• Genotypes 2 and 3 without cirrhosis or bridging fibrosis receive 24 weeks of treatment.
• Genotypes 2 and 3 with cirrhosis or bridging fibrosis receive 48 weeks of treatment.
• Genotypes 1, 4, 5 and 6 receive 48 weeks of treatment.

For people undertaking the 48 week course of treatment and having genotype 1, 4, 5 or 6 there is a requirement that certain objectives be achieved by week 12.  These are as follows:

• The hepatitis C virus is undetectable in the blood (negative PCR), OR
• The viral load has decreased by at least a 2 log drop.

Treatment regime

Combination therapy of pegylated interferon and ribavirin requires one subcutaneous (under the skin) injection per week and twice daily tablets of ribavirin for the duration of the treatment.  It is important that a routine be established and adhered to so that the drug levels in the body are maintained at a therapeutic level and the treatment has the greatest opportunity of effectiveness.  Therefore, planning is important in deciding which day of the week the pegylated interferon injection will be taken and the timing (morning and night) of the ribavirin dosing.

Side Effects

As with any medication, pegylated interferon and ribavirin treatment may have unwanted side effects.  All of the possible side effects of pegylated interferon and ribavirin are not experienced by everyone undertaking treatment and the degree to which they are experienced is variable.   It has also been noted that the severity of some side effects of pegylated interferon are reduced when compared to unpegylated interferon.  Some of the more common side effects include.