National Hepatitis C Resource Manual 2nd Edition

Treatments: Pegylated Interferon and Ribavirin

Page last updated: May 2008

In Australia, records show that 2,847 people with chronic hepatitis C infection were prescribed pegylated interferon and ribavirin combination therapy or pegylated interferon alone in 2006.


Interferons are proteins produced by the human body in response to any viral infection. The interferons used in the treatment of hepatitis C are synthetically manufactured and taken in higher doses than those which occur naturally in the body. Interferon therapy can boost a person’s immune response and inhibit viral growth. The sustained viral response (SVR) with interferon alone is between 15% and 20%. Modifying the interferon molecule by attaching polyethylene glycol extends the duration of the therapeutic effect of the drug so that dosing only needs to occur once a week instead of three times weekly. This form of interferon is known as pegylated interferon. Interferon is injected under the skin (subcutaneously) using a very fine needle.


Ribavirin is a drug taken orally that alters the body’s immune response to viruses. In the treatment of hepatitis C, it has been shown to be very effective in combination with interferon rather than as a treatment on its own.

Combination therapy

Combination therapy is the standard form of treatment for hepatitis C. It consists of pegylated interferon and ribavirin. Treatment consists of a 24 or 48 week course of pegylated interferon injections, self-administered once a week, plus ribavirin capsules taken twice daily.

How effective is combination therapy?

A person’s response to treatment is related to several factors:
  • genotype – people with genotypes 2 and 3 have been shown to have a higher response rate and in general need a shorter course of treatment than people with genotypes 1 and 4; Top of page
  • degree of liver scarring (fibrosis) – people with advanced liver disease respond less well to therapy and may require longer treatment courses;
  • amount of virus present in blood (viral load) – the lower the amount of virus, the more likely it is that therapy will clear the virus;
  • age – younger people are more likely to respond to treatment; and
  • sex – women are more likely than men to respond to treatment.
Expected outcomes for treatment with pegylated interferon and ribavirin are:

Genotypes 1 and 4: 48 week course of treatment 40–45% SVR
Genotypes 2 and 3: 24 week course of treatment80–90% SVR

Long-term follow-up studies (over 7–8 years) of people with a sustained response show that almost all continue to be HCV RNA negative by PCR.

If ribavirin cannot be taken, pegylated interferon can be used as monotherapy and it provides the following outcomes for people with long term infection:
Genotype 1 11–14% SVR
Genotype 2 and 3 36–49% SVR
(No data is available for genotype 4.)

How long should combination therapy continue?

Combination therapy can be demanding and it is important to monitor the overall health of the person undergoing treatment. Clinically, if a person with genotype 1 or 4 still has detectable levels of virus in their blood after 24 weeks of their 48 weeks of treatment, they only have a 2% chance of achieving a sustained viral response and their treatment should be stopped.

What are the side effects of combination therapy?

Combination therapy can cause a range of side effects, which vary in intensity from person to person. Side effects can also be dose-related; higher doses are often accompanied by more severe side effects. During the first few weeks of therapy many people develop a ‘flu-like’ illness (particularly pronounced after the first injection), together with fatigue, malaise, muscle aches and low-grade fever. This tends to subside as treatment continues.

Adverse effects of interferon and ribavirin

Interferon and ribavirin each have specific side effects. Top of page


  • malaise, nausea, fever, weight loss, diarrhoea, temporary hair loss
  • exacerbation of diabetes
  • loss of concentration, sleep disturbance, paraesthesiae (loss of sensation), exacerbation of epilepsy, visual loss (rare), deafness (rare)
  • depression, irritability, psychosis
  • low white blood cell count, thrombocytopenia Induction of autoimmunity
  • autoimmune thyroid disease, haemolytic anaemia, thrombocytopenic purpura (bleeding disorder), psoriasis, worsening of psoriasis, worsening of autoimmune hepatitis
  • arrhythmia, congestive failure


  • haemolytic anaemia
Respiratory tract
  • cough, dyspnoea, pharyngitis, sinusitis
Embryonic development
  • possible birth defect

New therapies for hepatitis C

Top of page The current gold standard for treatment of hepatitis C infection is combination therapy. However, several recent studies show that by more closely monitoring the viral load while on therapy, predictions can be made about the likelihood of a long-term response or SVR. For example, at present a viral load measurement at week 12 of therapy for persons with genotype 1 infection that is at least two logs10 lower than the baseline measurement predicts the person is likely to respond. In the future we are likely to see predictions made about long term response based on viral load measurements as early as week 4. The diagnosis of acute hepatitis C infection has also been highlighted because new studies show that using early monotherapy with pegylated interferon for 24 weeks prevents the infection becoming chronic in nearly all cases.

A number of people, particularly those infected with genotype 1, do not respond to combination therapy and others poorly tolerate the treatment because of adverse side effects. This emphasises the need for other therapies which are better tolerated and give an enhanced response rate. Several pharmaceutical companies have developed so-called first generation small molecule inhibitors directed against some of the virus-specific enzymes involved in virus multiplication, such as the protease and polymerase. Preliminary results show that they can inhibit hepatitis C virus replication but as monotherapy, resistance soon develops. Clinical trials are underway examining these agents in various combinations, including with pegylated interferon and ribavirin, to determine if they can improve response rates.


Note that vaccination against hepatitis A and B is recommended for people with hepatitis C, or with hepatitis C/HIV co-infection, who are not immune to hepatitis A or hepatitis B. See Chapter 3: Reducing Hepatitis C Transmission in the Community.

Hepatitis C treatment for people with hepatitis C and HIV co-infection

  • Co-infection with HIV leads to a more aggressive form of liver disease in hepatitis C infected patients. Response to treatment is also reduced in persons with a HIV co-infection compared to those with hepatitis C infection only.
  • People with low CD4 counts are those in greatest need of hepatitis C therapy. The aims of therapy in advanced HIV should be to delay progression of liver disease rather than to achieve eradication of both viruses.
  • The potential interaction between the drugs used to treat HIV infection and the drugs used to treat hepatitis C can lead to hepatotoxicity and this should be monitored closely
  • The timing and sequence of treatment for hepatitis C and HIV co-infection remains a complex issue and specialist advice from an infectious diseases physician is required.

Quality of life issues during treatment

For some people, the physical and psychological side effects of combination therapy can be overwhelming. Given that treatment can last for up to twelve months, some people find it hard to continue to work and many people experience difficulties in their personal and professional lives. Health care workers need to be aware of the social and psychological pressures that can result from a course of combination therapy and, where appropriate and available, refer people to treatment support groups. Top of page

In some people, treatment can have a considerable impact on their mental health, causing mood swings, anxiety and depression or exacerbating existing conditions. Mental health status should be closely monitored throughout treatment.

To help people minimise the negative side effects that can be associated with treatment, appropriate support mechanisms should be an essential feature in the clinical setting. Additionally, hepatitis councils offer confidential telephone information lines (national telephone number 1300 437 222) and support groups that people on treatment may find useful. See Chapter 5: Living with Hepatitis C; and Contacts Section in Resources.

Access to treatment for Aboriginal and Torres Strait Islander people

It appears from the limited data available that Aboriginal and Torres Strait Islander people are accessing and successfully completing treatment at a much lower rate than non-Aboriginal people. This is due to a number of factors:
  • a limited number of prescribers in Aboriginal Health Services;
  • lack of support;
  • lack of knowledge about hepatitis C; and
  • remote and rural locations make access to treatment difficult.

Access to treatment for people in rural or remote areas

Access to treatment for hepatitis C is currently restricted to specialist services linked to major regional hospitals. Many people live too far away from a regional-based treatment centre to have easy access to treatments under Section 100 of the Pharmaceutical Benefits Scheme (a government subsidised treatment schedule). Shared Care and Enhanced Primary Care (EPC) initiatives are gradually expanding through rural Australia, allowing more people with hepatitis C to access treatment and have their care managed in a partnership arrangement between specialists, GPs and other health care services. The expansion of these programs nationwide will ensure greater access to specialised care and treatment services. However, under current regulations, initial prescriptions for treatment can only be issued by a specialist centre. Top of page

Access to treatment for people who inject drugs

People who inject drugs, including those who are using drug substitution therapy, have been able to access hepatitis C treatment under Section 100 of the Pharmaceutical Benefits Scheme since 1999. All people seeking treatment should be assessed using the Section 100 PBS criteria. Many health care workers have not been trained or supported to work with people who inject drugs. As a result, prejudices and past experience may lead health care workers to treat people who inject drugs less favourably. The ability to comply with treatment, the cost of treatment, support while on treatment, and access to treatment are issues identified by all people with hepatitis C. Drug and alcohol services are increasingly addressing hepatitis C-related issues with their clients by offering education, testing, counselling and referral to hepatitis C treatment services. See Chapter 7: Preventing Discrimination and Reducing Stigma and Isolation.