Does a rapid decline in the hematological and biochemical parameters induced by interferon and ribavirin combination therapy for the hepatitis C virus predict a sustained viral response?
OBJECTIVE
To analyze whether rapid myelosuppression and a decrease in alanine aminotransferase (ALT) induced by standard interferon (IFN) and ribavirin (RBV) combination therapy predict a sustained viral response (SVR) in hepatitis C virus patients.


METHODS
Data from 111 patients (mean age 48.1 years) with chronic hepatitis C virus were retrospectively analyzed. All patients were treated with the same initial doses of IFN and RBV combination therapy. The following laboratory values were measured at baseline, and then at weeks 2, 4, 8, 12 and 24 of treatment: hemoglobin, white blood cells (WBCs), neutrophils, platelets and ALT. A delta value was then calculated for each interval from baseline (baseline values minus two weeks, etc). The delta value of each variable was then compared between the responders and nonresponders using Wilcoxon's signed rank test.


RESULTS
Sixty patients (54%) achieved an SVR. There were no significant differences between the responder and nonresponder groups for baseline variables. The delta value of ALT was the only significant marker in the prediction of an SVR. The mean +/- SD delta values for the ALT at week 2 of treatment were 71+/-92 U/L and 44+/-85 U/L for the responders and nonresponders, respectively (P<0.0046). At week 4, the values were 101+/-96 U/L and 84+/-100 U/L for the responders and nonresponders, respectively (P<0.0154). The decline was then calculated for the ALT as a percentage decrease from baseline: at weeks 2 and 4, the decreases were 64% and 66%, respectively, for the responders, and 43% and 41%, respectively, for the nonresponders. At week 2, the delta values for WBC count were found to be significant in predicting failure to achieve an SVR, with mean +/- SD delta values of 0.85 x 10(9)/L+/-1.48 x 10(9)/L and 1.53 x 10(9)/L+/-2.16 x 10(9)/L for the responders and nonresponders, respectively (P<0.0173). The same trend emerged at two weeks for neutrophils: 0.72 x 10(9)/L+/-1.33 x 10(9)/L for the responders and 1.02 x 10(9)/L+/-1.20 x 10(9)/L for the nonresponders (P<0.0150). The delta values were insignificant for hemoglobin, lowest hemoglobin values and platelets.


CONCLUSIONS
The decline rates of ALT from baseline to week 2 and 4 of IFN and RBV combination therapy are good predictors of an SVR. A significant drop in WBC and neutrophil values is a predictor of failure to achieve an SVR. The hemoglobin, platelets and lowest hemoglobin values failed to predict an SVR.
Turbide
C
C
McGill University Health Centre, Montreal, Canada.
Soulellis
C
C
Deschênes
M
M
Hilzenrat
N
N
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage*; D001772:Blood Cell Count; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006454:Hemoglobins; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D006454:Hemoglobins; D012254:Ribavirin; D007372:Interferons; D000410:Alanine Transaminase