Man With Hepatitis C Infection: Making Treatment Decisions

By ANDRÉ N. SOFAIR, MD, MPH | April 1, 2006

Yale University

Dr Sofair is assistant professor of medicine at Yale University School of Medicine, New Haven, Conn, and a principal investigator in the Connecticut Emerging Infections Program, a collaborative effort of the Connecticut Department of Public Health and the Centers for Disease Control and Prevention.

THE CONSULTANT'S CHOICE The wise choice here is A. Ribavirin(Drug information on ribavirin) frequently causes hemolytic anemia. In up to 10% of patients, the situation is serious enough to necessitate a reduction in dosage.¹⁶ However, a reduction in ribavirin dosage is associated with a decreased virologic response²⁹; thus, it is appropriate to reduce the dosage or discontinue the drug altogether only when necessary. A reduction in ribavirin dosage to 600 mg/d is advised when hemoglobin levels decrease 2 g/dL or more over a 4-week period in patients with cardiac disease, or when the level drops to less than 10 g/dL in all others.³⁰ Erythropoietin(Drug information on erythropoietin) can limit ribavirin-associated anemia and enable some patients to continue with the standard dosage.³¹ Permanent discontinuation of ribavirin may be necessary in patients with cardiovascular disease whose hemoglobin level is persistently below 12 g/dL or in anyone whose hemoglobin level is consistently below 8.5 g/dL. Flu-like symptoms are very common in patients receiving interferon therapy. They usually abate as therapy continues, and their presence does not justify a reduction in dosage or discontinuation of the medication. Our patient remained on his initial treatment regimen, and his hemoglobin level remained stable (without intervenion) for the duration of therapy. A viral load measurement taken after 24 weeks revealed undetectable levels of HCV. The patient successfully completed 48 weeks of treatment, and a viral load measurement taken 6 months post-treatment also showed undetectable levels. In those who demonstrate a sustained virologic response, as our patient did, infection recurs in fewer than 10% of patients during the subsequent 5 to 10 years. Histologic injury also appears to improve over time.^32,33

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CLINICAL PEARLS

Unless contraindicated, treatment with interferon and ribavirin is recommended for patients with HCV infection in whom liver biopsy reveals at least grade 2 inflammation and stage 1 fibrosis. Although patients with subclinical cirrhosis may benefit from treatment, those with decompensated cirrhosis should not be treated.
Genotype is the most important predictor of response to therapy. Patients infected with genotype 1 (the most common type in the United States) have a sustained response rate approximately one half that of patients infected with other genotypes.
Genotype also affects the length of therapy. Patients infected with genotype 2 or 3 can be treated successfully in 24 weeks. In those with genotype 1 infection, extending the duration of therapy from 24 to 48 weeks doubles sustained response.
Psychiatric side effects, including irritability, emotional lability, depression, and even suicidal ideation, occur in at least 20% of patients treated with interferon. Consider a pretreatment psychiatric consultation for any patient with a history of psychiatric illness or substance abuse, a family history of psychiatric disease, or other risk factors for depression (such as multiple comorbidities or use of medications that predispose to depression). Regular screening for depression is mandatory throughout treatment.
Pegylated interferon offers better bioavailability, a longer half-life, and better response rates than conventional interferon.
Ribavirin often causes hemolysis, with decreases in hemoglobin levels of 2 g/dL to 4 g/dL. Erythropoietin can limit ribavirin-associated anemia and make it possible for some anemic patients to continue with the standard dosage. Permanent discontinuation of ribavirin therapy may be necessary in patients with cardiovascular disease whose hemoglobin level is persistently below 12 g/dL or in anyone whose hemoglobin level is consistently below 8.5 g/dL.
Ribavirin can cause fetal abnormalities and should not be used by either men or women who cannot use reliable birth control during treatment and for at least 6 months thereafter.

From June 10-12, 2002, the National Institutes of Health will convene a consensus development conference to update its 1997 recommendations on the management of hepatitis C. A draft of these recommendations will be posted at http://consensus.nih.gov on June 12.

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Man With Hepatitis C Infection: Making Treatment Decisions

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