Ontario Hepatitis Treatment

Indications for treatment

Any patient infected with hepatitis C should be considered for treatment. Thus hepatitis C itself is the indication for treatment. Thereafter, there may be reasons not to treat. These include;

• Patient wishes: Patients may be scared of side effects. There may be personal reasons for not wanting to have to deal with the side effects at a particular time (e.g., going away to school, or new job, etc).
• Contraindications present ( see below)
• Patient considers the response rate inadequate and wishes to wait for newer treatments with better response rates to come along.

If there are no contraindications to treatment but the patient does not wish to take treatment for any reason it is recommended that an assessment be made of the amount of fibrosis present. For patients in whom the disease is of recent onset and in whom none of the factors that are known to accelerate disease progression area present significant fibrosis is unlikely, so a biopsy is probably not necessary. However, for patients infected for longer periods (e.g., over 10 years) a biopsy might be required to assess fibrosis. If the fibrosis is at stage 2 or higher treatment is strongly recommended.

Contraindications to treatment

Pregnancy

• This is a major absolute contraindication
• Ribavirin has been shown to be teratogenic in experimental animals. However, no case of ribavirin-induced fetal abnormality has yet been described in humans.

The remaining contraindications are relative contraindications. Treating these patients is more difficult than usual and is best left to expert centers.

Advanced liver disease (cirrhosis with some degree of liver failure)

• Treatment of these patients can make the liver disease worse
• Patients with advanced cirrhosis are prone to life-threatening infections on interferon treatment.

Depression with suicidal ideation

• Interferon can cause depression. Untreated, unstable depression is an absolute contraindication, but this condition is modifiable with treatment.
• Some patients who were injection drug users many years ago may have attempted suicide during the period of injection drug use. This has less significance that a recent attempt at suicide.

Active autoimmune disease

• Interferon can trigger autoimmune diseases, and can make active disease worse. This is because it is an immune stimulant.

Severe anemia

• Ribavirin causes anemia as a predictable side effect. Thus in patients who start off with low hemoglobin the risk of symptomatic declines in hemoglobin is high. However, there are ways of supporting these patients (e.g, with transfusion). This requires expert care.

Active injection drug use in an unsupervised setting

• Active drug use is not a contraindication to treatment. However, if the patient is unable to comply with treatment because of current social circumstances (e.g., homeless), or has a high likelihood of re-infection treatment will be unlikely to be effective.

Renal failure

• Ribavirin is excreted by the kidney and is not dialyzable. There it will accumulate in these patients and exacerbate the anemia. Both interferons are also excreted by the kidney to varying extents, but the dose can be adjusted for renal failure.

Coronary artery disease

• These patients are at risk for cardiac ischemia in the presence of ribavirin-induced anemia. The same is true for vascular disease elsewhere (e.g., peripheral vascular disease, transient ischemic attacks, etc.

Neutropenia

• Interferon is a bone marrow suppressant and will therefore reduce the production of neutrophils. The product monographs indicate that patients in whom the neutrophils count is less than 1.0 x109/mL should not be started on interferon. However, expert opinion is that these patients can be treated. This requires some experience so as not to withdraw treatment too early.

Thrombocytopenia

• Interferon will also reduce the platelet count. The product monograph suggest that patients with a platelet count below 75 x109/mL should not be treated. However, expert opinion is that patients with lower platelet counts as low as 30 x109/mL can be treated.

Major depression

• Untreated depression is an absolute contraindication to treatment. However, patients with depression well controlled on therapy can be treated. Patients with a history of depression who are not currently depressed and not currently on treatment can also be treated. They may require antidepressants while on treatment, but it is not always necessary to start anti-depressants prophylactically.

Major psychosis

• Uncontrolled major psychosis such as schizophrenia are absolute contraindications to treatment. However, patients with schizophrenia who are well controlled on or off medication can be treated.

Problems with anger management

• Patients who cannot control anger should not be treated. Interferon can induce irritability, and episodes of violence have been recorded in those who have difficulty with anger management. Sometimes antidepressants can be used to control anger, but this should be undertaken in conjunction with a psychiatrist.

Solid organ transplantation (other than liver)

• Interferon is an immune stimulant that will enhance rejection is solid organ transplantation, except liver transplantation. Patients with long standing bone marrow transplantation can be treated without fear of enhancing graft-vs host disease.