Early and accurate prediction of Peg-IFNs/ribavirin therapy outcome in the individual patient with chronic hepatitis C by modeling the dynamics of the infected cells.
A novel biomathematical model that analyzes the combined alanine transaminase (ALT) and viral-load kinetics during the first month of pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy was successfully applied in 90 of 97 (93%) chronic hepatitis C patients in order to compute the number of infected cells at the end of therapy (I(eot)). The I(eot) indices were lower in sustained virological responders than in relapsers (RELs) and nonresponders (NRs) (median values: 31 vs. 2,190 vs. 1,090,000; P < 0.001), and were independently associated with treatment outcomes (P = 0.003). A threshold of 250 I(eot) was shown to identify sustained virological response (SVR) with high positive predictive value (93%) and good diagnostic accuracy (81%). The time taken to attain 250 I(eot) ranged from 3 to 11 months in patients with hepatitis C virus (HCV) genotypes 2 or 3 and from 3 to 18 months in those with HCV genotypes 1 or 4. Overall, the duration of therapy would have been 49 months less than that suggested by the most recent algorithms based on a rapid virological response (RVR) at week 4.
Colombatto
P
P
UO Epatologia SSN, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Ciccorossi
P
P
Maina
A M
AM
Civitano
L
L
Oliveri
F
F
Coco
B
B
Romagnoli
V
V
Bonino
F
F
Brunetto
M R
MR
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008962:Models, Theoretical; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000302:isolation & purification; D012372:ROC Curve; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D004337:Drug Carriers; D007376:Interleukin-2; D012367:RNA, Viral; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase