Rapid Virological Response at Week 4 Is the Best Predictor of Treatment Outcome in Patients with Chronic Hepatitis C

It is well established that HCV genotype and baseline HCV RNA are good predictors of sustained virological response (SVR) in patients in clinical trials of pegylated interferon alfa plus ribavirin. However, limited knowledge is available on predictors of SVR in the general population managed in routine clinical practice.

At the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), researchers presented data from an analysis of predictors of sustained response in a "real world" setting.

The study included 408 consecutive patients treated with pegylated interferon alfa-2b (PegIntron) plus ribavirin (221 treatment-na-ves; 125 prior non-responders, and 62 prior relapsers.

Patients with HCV genotypes 1 or 4 were treated for 48 weeks and those with genotypes 2 or 3 were treated for 24 weeks using 1.5 mcg/kg/week pegylated interferon alfa-2b plus 800-1200 mg/day weight-based ribavirin.

Serum HCV RNA was measured at baseline, week 4, week 12, the end of treatment, and 6 months after the end of treatment using the quantitative Versant HCV 3.0 Assay (bDNA). Samples below the limit of quantification were tested with the Versant HCV RNA Qualitative Assay (TMA). SVR was defined as undetectable serum HCV RNA by TMA at the end of a 6-month post-treatment follow-up period. Early viral kinetics were analyzed at weeks 1-4 in a subgroup of 78 patients.

The characteristics included in the logistic regression analysis were baseline HCV viral load (< vs > 400 x 103 IU/mL), HCV genotype (1, 2, 3, 4, 5), sex, age (< vs > 45 years), liver histology grade (A0-A1 < vs > A2-A3), fibrosis stage (F0-F2 < vs > F3-F4) assessed by Metavir score, serum ALT, pre-treatment status, rapid virological response at week 4 (RVR-4)(TMA undetectable) and rapid virological response at week 12 (RVR-12) (> 2 log drop in viral load).

Results

• Overall SVR rate was 46%:
• 53% in treatment-naive patients;
• 25% in non-responders;
• 65% in relapsers.
• In the overall population, factors significantly associated with SVR were: RVR-4: odds ratio (OR) 26.4 (P<0.0001);
• Age: OR 2.6 (p=0.005);
• Fibrosis: OR 2.1 (p=0.04).
• Lack of RVR-12 was significantly associated with non-response (OR 51.2; p<0.0001).
• In treatment-naive patients, factors significantly associated with SVR were:
• RVR-4: OR 16.2 (p=0.001);
• Age: OR 3.2 (p=0.001);
• Fibrosis: OR 3.9 (p=0.001).
• In non-responders, only lack of RVR-12 (OR 16.9; p=0.007) was significantly associated with non-response.
• The slopes of early viral kinetics were significantly different in SVR and non-SVR patients (p<0.0001), but were not different in treatment-naive and treatment-experienced patients who achieved SVR.

Conclusion

Based on these findings, the researchers concluded that RVR at week 4 of therapy was the strongest independent factor for prediction of SVR. Lack of early virological response at week 12 was the strongest predictor of lack of SVR.

"Therefore," they noted, "monitoring of therapy should include both detection of serum HCV RNA at week 4 with a sensitive assay (TMA) to predict SVR and quantification of HCV RNA at week 12 to predict non-SVR."

INSERM U773- CRB3 Université paris VII, Hopital Beaujon, Clichy, France; Service d'Hépatologie, Hopital Beaujon, Clichy, France.

11/13/07

Reference
M Martinot-Peignoux, S Maylin, R Moucari, and others. Rapide Virological Response at Week 4 is the Best Predictor of Treatment Outcome in Patients with Chronic Hepatitis C: A Multivariate Analysis. 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007). Boston, MA. November 2-6, 2007. Abstract. Abstract 303.