Management of adverse reactions to chronic hepatitis C treatment

Abstract

Most patients with chronic hepatitis C virus (HCV) infections are asymptomatic or display few symptoms, but some experience adverse reactions to therapy. The severity of these adverse effects depends mainly on drug dosage, frequency of administration, and route of administration. Severe reactions to treatment are experienced in 10%–15% of cases. 1 The practical significance of the adverse effects of drugs is that they lower the quality of life of patients, which results in fewer adherences to anti-HCV therapy and a lower virological response. Systemic side effects occur in 30%–50% of cases and include flu-like symptoms, fatigue, headache, thyroid dysfunction (hypothyroidism or hyperthyroidism), anorexia, digestive disorders, central nervous system disorders including depression, hematological disorders because of bone marrow dysfunction, and anemia. In most cases, the symptoms only cause slight discomfort or are easy to manage with symptomatic treatments, dose adjustments, or adjustment of the duration of therapy. About 10%–15% of patients discontinue treatment with interferon plus ribavirin because of adverse effects. The rate of discontinuation of treatment increases as the duration of treatment increases and is elevated when interferon plus ribavirin treatment is used. 1 The principal adverse effects of interferon are pseudoflu symptoms, fatigue, anorexia, weight loss, diarrhea, alopecia, insomnia, depression, anemia, neutropenia, thrombocytopenia, retinopathy, thyroiditis, and Hashimoto thyroiditis. Adverse effects of ribavirin. The most frequent side effect of ribavirin is hemolytic anemia, which occurs in up to one-third of patients. Ribavirin causes hemolysis because ribavirin triphosphate is concentrated by erythrocytes. 2 The second most frequent side effect is pruritus, which rarely results in discontinuation of treatment. H 1 antihistamines should be administered when pruritis occurs. During treatment with ribavirin, bilirubin and uric acid levels increase in about 10%–25% of patients. These side effects disappear 4–7 weeks after discontinuation of therapy. Other side effects of ribavirin are teratogenicity, cough, dyspnea, and rash. 1 The adverse effects of pegylated interferon alfa plus ribavirin are the same as those of standard interferon alfa plus ribavirin. Pseudo-flu symptoms are more frequent when pegylated interferon alfa is administered in high doses, probably because the dose of interferon is greater. As with pegylated interferon alfa monotherapy, pegylated interferon alfa plus ribavirin results in a higher incidence of localized erythema, which is generally light and does not require discontinuation of treatment. The occurrence of anemia, an adverse effect of ribavirin, is similar when ribavirin is given in combination with pegylated interferon alfa or regular interferon alfa. The dose of ribavirin is reduced in 20%–25% of patients because of anemia, in 20% of patients because of neutropenia, and in less than 5% of patients because of thrombocytopenia, but discontinuation of ribavirin treatment is rare.