Long‐term retreatment in chronic hepatitis C patients who were non‐responders to an initial course of interferon‐α2b

Abstract

Nineteen patients with chronic hepatitis C who were virological non-responders (seven responder/relapse and 12 no response) to an initial 24-week course of interferon-alpha 2b (IFN-alpha 2b) at a dose of 3 million units (MU) thrice weekly were retreated for an additional 48 weeks at the same dosing schedule and followed-up for another 24 weeks post-therapy. At the end of follow-up (week 72), six (32%) of the 19 patients were hepatitis C virus (HCV) RNA negative and were virological complete responders to retreatment. The viral genotypes in these six patients included two each with 1b and 3a, one with 2b, and another with 2a/2b; five of the six virological responder patients had cirrhosis. Significant predictors for successful retreatment included lower baseline HCV RNA concentrations prior to the first course of therapy, 2 log10 reductions in serum HCV RNA during the initial treatment and classification into the virological 'responder/relapse' category after the first course of IFN (P < 0.01 for all observations). When the above factors were used to construct a predictive model to determine response to retreatment, it was found that the absence of a 2 log10 drop in HCV RNA concentrations during the first course of IFN therapy was the most reliable indicator of non-response to retreatment (likelihood ratio = 10, P = 0.0014). In addition, the presence of HCV RNA at week 12 of retreatment was 100% predictive of virological non-response to the 48-week course of therapy. Our findings indicate that an additional 48-week course of IFN-alpha 2b therapy at 3 MU thrice weekly will achieve a virological complete response in 60% of patients who had a 2 log10 drop in HCV RNA during their first course of treatment, and measurement of week-12 HCV RNA during retreatment to identify non-responders is beneficial to patients as well as being cost-effective. Thus, a second course of IFN remains a viable option in a subgroup of non-responder patients, regardless of genotype or the presence of compensated cirrhosis.

Improved Version 2.0 Qualitative and Quantitative AMPLICOR Reverse Transcription-PCR Tests for Hepatitis C Virus RNA: Calibration to International Units, Enhanced Genotype Reactivity, and Performance Characteristics

“…The decrease in viral load early after treatment initiation appears to have more prognostic value than baseline viral load (11,13,25,35,36). Thus, measuring the early viral load response may prove useful for guiding changes in therapeutic regimens in individual patients (3,25,33,38) and for comparing the efficacy of new treatment regimens. During interferontreatment, viral load often drops rapidly to low levels (25,38).…”

“…Both qualitative and quantitative tests for hepatitis C virus (HCV) RNA have contributed to our understanding of the natural history of HCV infection. Quantitative tests are used to measure viral burden for patient identification and stratification (1,4,5,9,20,25) and to provide real-time information for modifying treatment (3,25,33,38). Qualitative tests are used to diagnose infection (6,20,22,30) and may serve as a test of cure, where it may suffice to demonstrate that the viral RNA load falls below a critical threshold associated with long-term clinical benefit (14).…”

Performance Characteristics of a Quantitative, Homogeneous TaqMan RT-PCR Test for HCV RNA

“…Nucleic acid amplification tests for HCV RNA have contributed to our understanding of the natural history of hepatitis C virus (HCV) infection and to the clinical management of chronic hepatitis C. Quantitative viral load tests are used for prognosis, [1][2][3][4][5][6][7][8][9] for evaluating new treat-ment regimens, 10 and for modifying treatment 11 or deciding whether to administer follow-up treatment. 12 A recent analysis of data from two multicenter studies indicates that pretreatment viral load, together with genotype, sex, age, and extent of fibrosis, can be used to decide whether patients should be treated with interferon plus ribavirin for 24 or 48 weeks. 13 Qualitative tests are used to diagnose infection 5,14 -16 and to detect a sustained response to antiviral therapy, 5,14 which is associated with long-term clinical benefit.…”

Meta‐analysis: combination therapy with interferon‐α 2a/2b and ribavirin for patients with chronic hepatitis C previously non‐responsive to interferon

“…Forty‐six articles were considered for evaluation. Of these, 11 were excluded because they were not controlled studies, 19–29 10 because they used other types of IFN, 30–39 seven due to a ribavirin dosage below 800 mg/day, 40–46 two because they used less than 6 months of combination therapy, 47 , 48 and two because of the inclusion of false non‐responders 49 ,. 50 Another two studies were not included as the control group was given amantadine as well as IFN 51 ,.…”