The Role of Epidemiology in Predicting Response to Antiviral Therapy

Currently, the most effective initial therapy for treatment of patients with chronic hepatitis C virus (HCV) infection is a combination of interferon a-2b plus ribavirin. This combination regimen produces sustained virologic responses in 33% or 41% of treatment-naïve patients when given for 24 or 48 weeks, respectively.

In general, genotype 1-infected patients require 48 weeks of therapy, whereas genotype non-1 patients require only 24 weeks of interferon/ribavirn. A number of other viral and host factors have recently been identified and may help predict response to and duration of therapy, allowing combination therapy to be tailored more effectively. In addition to HCV genotype non-1, other factors that predict a good response to interferon/ribavirin include age = 40 years, female gender, viral load = 2 million copies/mL, and no or portal fibrosis. The most powerful of these factors appears to be the HCV genotype. Age at infection, gender, and the degree of fibrosis have also been shown to portend a poorer prognosis in terms of disease progression in chronic HCV infection.

Data derived from post-hoc analysis indicate that patients with <3 favourable response factors seem to benefit from continuation of combination therapy for 48 weeks. Also, patients with genotype 1 infection and low viral load have a significantly higher response rate when they receive 48 weeks of therapy compared with 24 weeks. These factors should be taken into account when considering the duration of therapy with interferon/ribavirin. The value of these tailored regimens of interferon/ribavirin should be studied prospectively.

African-American patients with chronic HCV infection have lower response rates than Whites to interferon monotherapy and are predominantly infected with genotype 1. However, the response rates to combination therapy, when adjusted for genotype, are similar for African-American and White patients (22% vs 23%, respectively). These observations suggest that the impaired responsiveness of African-American patients to interferon monotherapy can be partially overcome by treatment with interferon/ribavirin combination therapy.

Case Study

A 45-year-old male African-American accountant was diagnosed at an annual physical examination with a symptomatic HCV infection. His liver enzyme levels were elevated (alanine transaminase [ALT] 88 IU/L); CBC was normal; and HCV RNA was 1.2 million copies/mL, genotype 1. A biopsy revealed moderate inflammation and stage 2 fibrosis. The patient reported that he does not drink alcohol.

Treatment with interferon/ribavirin was initiated. Within 12 weeks, ALT was normal, and at week 24, HCV RNA was undetectable. Therapy was continued for an additional 24 weeks. At the end of treatment, the patient’s ALT was again normal and HCV RNA was still undetectable. At 3 months posttherapy, ALT was 78 IU/I, and HCV RNA was 1.4 million copies/mL.

John G. McHutchison, MD

Suggested Readings

McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998;339:1485-1492.

McHutchison JG, Poynard T; Gordon SC, et al for the International Hepatitis Interventional Therapy Group. The impact of race on response to antiviral therapy in patients with chronic hepatitis C: [abstract], Hepatology. 1999;30:302A.

Poynard T. Marcellin P, Lee SS, et al. Randomised trial of interferon-alpha 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon-alpha 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancer 1998;352:1426-1432.

Poynard T, McHutchison JG, Goodman z, Ling MH, Albrecht J. is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first-line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group. Hepatology. 2000;31:211-218.

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