Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response.
BACKGROUND
The viral load and subtype of hepatitis C virus (HCV) are predictors of the efficacy of interferon (IFN) therapy. The kinetics of HCV during IFN therapy have been described recently, suggesting that HCV infection is highly dynamic. These observations have raised the issue as to whether early monitoring of the viral load can help guide IFN therapy.


METHODS
We measured HCV-RNA levels at 0, 24 and 48 h after the start of IFN-alpha treatment (10 MU daily for 2 weeks and then three times weekly for 22 weeks) or IFN-beta treatment (6 MU daily for 6 weeks). Then we analyzed the relationship between HCV kinetics and therapeutic response using stepwise multivariate logistic regression analysis.


RESULTS
The exponential decay slope of the viral load during the first 24 h, not the first 48 h or the next 24 h, was a predictor of viral eradication at 6 months after completion of the treatment (sustained response; P = 0.0023). This decay slope was not affected by the HCV serotype or the type of IFN used. Initial viral load and HCV serotype were also predictors, as reported previously (P < 0.0001 and P = 0.0347, respectively). We also proposed a model using a prognostic index that predicted a sustained response with more than 80% sensitivity, specificity and efficacy in an independent and external group of patients.


CONCLUSIONS
This study demonstrated that the exponential decay slope of the viral load during the first 24 h was an important predictor of the response to IFN therapy as well as the initial viral load and HCV serotype. The model may also be useful for the clinical management of IFN therapy.
Nakamuta
M
M
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nakamuta@intmed3.med.kyushu-u.ac.jp
Fukutomi
T
T
Shimohashi
N
N
Kinukawa
N
N
Uchimura
K
K
Tada
S
S
Motomura
K
K
Enjoji
M
M
Kato
M
M
Iwamoto
H
H
Tanabe
Y
Y
Imari
Y
Y
Sakamoto
S
S
Sakai
H
H
Nawata
H
H
D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D012680:Sensitivity and Specificity; D013997:Time Factors; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D016899:Interferon-beta