THE CONSULTANT'S CHOICE The optimal choice here is C. Interferon alone produces sustained response rates of just 10% to 20%^20,21 and, therefore, is indicated as monotherapy only in patients with contraindications to ribavirin(Drug information on ribavirin). The duration—and efficacy—of combination therapy are determined by a patient’s HCV genotype, of which there are at least 6 distinct types. Genotypes 1, 2, and 3 are found most often in the United States; genotype 1 is the most common. Genotype 4 is largely confined to the Middle East and northern Africa, genotype 5 to South Africa, and genotype 6 to Asia.²² Genotype is the most important predictor of response to therapy. Patients infected with genotype 1 have a sustained response rate (persistently normal aminotransferase concentrations and absence of viral RNA at the end of therapy and for at least 6 months thereafter) approximately 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 with 24 weeks of therapy. In those with genotype 1 infection, the percentage who demonstrate sustained response can be doubled by extending the duration of therapy from 24 to 48 weeks. A 48-week course of therapy is therefore recommended for our patient, who is infected with genotype 1A. Some studies have shown that patients with higher pretreatment viral loads may respond better to longer treatment regimens. However, because viral load fluctuates over time and because assays of viral load are not standardized, this variable is not currently used to determine length of therapy.⁸ DRUGS AND DOSAGES Combination therapy with interferon and ribavirin remains the standard of care for patients with HCV infection. Ribavirin, an oral nucleoside analogue, is active against RNA and DNA viruses. Although it has little effect as monotherapy, it augments the efficacy of interferon. Pegylated interferon, which is created by attaching a molecule of polyethylene glycol to interferon, results in better bioavailability, a longer half-life, and better response rates than conventional interferon. Pegylated interferon was approved by the FDA as monotherapy for hepatitis C in January 2001 and as combination therapy with ribavirin in August 2001. Sustained virologic and histologic response to pegylated interferon monotherapy is superior to that seen with standard interferon and similar to that seen with standard interferon/ribavirin therapy.^23-25 However, since ribavirin also augments the effect of pegylated interferon, combination therapy with these 2 agents is the treatment of choice unless contraindicated. The average sustained response rate for conventional interferon/ ribavirin is 40%; for pegylated interferon/ribavirin, 60%. Patients infected with genotypes 2 and 3 have a sustained response rate with pegylated interferon/ribavirin as high as 88%; those infected with genotype 1 have a response rate of 48%.^26-28 Our patient can expect a sustained response rate of 30% to 50%, depending on the type of interferon used. The standard dosing regimen for conventional interferon is 3 million units subcutaneously 3 times per week; for pegylated interferon, 1.5 µg/kg subcutaneously once weekly. Ribavirin is taken orally; 1200 mg/d for patients who weigh at least 75 kg, and 1000 mg/d for those who weigh less than 75 kg. Our patient has begun therapy with conventional interferon (pegylated interferon was not available) and ribavirin. WHAT WOULD YOU DO NOW?
A. Check CBC count, LFTs, and TSH regularly.
B. Screen for depression regularly; also check CBC count, LFTs, TSH, and viral load on a regular basis.
C. After 24 weeks, screen for depression and check CBC count, LFTs, TSH, and viral load.
D. Screen for depression regularly; check CBC count, LFTs, and TSH on a regular basis; check viral load after 24 weeks.