Viral Kinetics Can Quickly Predict Sustained Virological Response in Hepatitis C Patients with Normal ALT Treated with PegIntron plus Ribavirin

Treatment is recommended for HCV patients with normal levels of alanine transaminase (ALT) only in an effort to achieve viral eradication. HCV viral kinetics during anti-HCV therapy is comprised of a 2-phase decline. The second (slow) delta phase is related to infected cell loss. The delta phase is predictive of sustained virological response (SVR) and may be estimated by reduction of viral load.

In patients with normal ALT, a good estimate of delta phase is required to determine as soon as possible the need to continue treatment.

The objective of the present French study, presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA (November 2-6, 2007), was to determine the earliest and optimal time when decline of HCV log viral load becomes the best estimate of delta phase in patients with normal ALT prospectively treated with pegylated interferon alfa-2b (PegIntron) plus ribavirin for 6 or 12 months.

The prediction of viral kinetics was expressed by the AUROC curves. Viral load was assessed at 1, 4, and 8 hours; days 1 to 4, 7, 14, 21, and 28; and months 2 and 3 during treatment.

Results

• 24 patients (17 with genotype 1) were included.

• The median ALT level was 26 +/- 6 IU/L. No patients had significant liver fibrosis.

• The median baseline HCV viral load was 284,500 IU/mL.

• 62% achieved SVR (53% for genotype 1 patients).

• Overall, reduction of viral load at day 21 was the earliest time estimating SVR (AUROC curve of log viral load: 0.848 +/- 0.086; P<0.0001).

• However, day 28 had the highest AUROC curve of log viral load for estimating SVR (0.981+/- 0.02; P<0.0001).

• Months 2 and 3 measurements did not have better AUROC curves of log viral load than that at day 28.

• In a sensitivity analysis restricted to genotype 1 patients, reduction of viral load at day 28 had a better predictive value for SVR than reduction at day 21 (AUROC curves of log viral load: 0.962 +/- 0.04 vs 0.759 +/- 0.13; P=0.02).

• No SVR was observed in genotype 1 patients with a decline of viral load <1 log from baseline to day 28.

• In terms of optimal cut-off in genotype 1 patients, a viral load decline of >2 log at day 28 was the best predictor of SVR (sensibility 95%, specificity 76%, PPV 85%, NPV 91%).

• 40% of the patients were below this cut-off and had < 10% probability of SVR.

• 60% of the patients were above this cut-off and had > 80% probability of SVR.

Conclusion

Based on these findings, the researchers concluded, "In HCV genotype 1 patients with normal ALT, reduction of VL at day 28 is the best estimate of the delta phase." Furthermore, they noted, "As viral eradication is the only aim, the use of this endpoint may avoid waiting 3 months to decide treatment discontinuation in genotype 1 patients with low probability of SVR."

Hepatology, Hôpital Huriez, Lille, France; Hepatology, Hôpital de Jolimont, Haine- Saint-Paul, Belgium; INSERM U795, Lille, France; Virology, Hôpital Calmette, Lille, France; Virology, CHU, Amiens, France.

11/20/07

Reference
P Deltenre, V Canva, A Louvet, and others. Viral Kinetics Can Quickly Predict Sustained Virological Response in HCV Patients with Normal ALT Treated with Pegylated IFN Aifa-2b and Ribavirin: A Prospective Study. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA. November 2-6, 2007. Abstract 312.