Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4.
BACKGROUND
The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited.


OBJECTIVE
To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4.


METHODS
Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 +/- 9 years, and mean weight 74 +/- 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 x 10(6) copies/ml (8.4 x 10(5) iu/ml) and median was 2.15 x 10(6) copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000-1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis.


RESULTS
End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA > or =2 x 10(6) SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 x 10(6) (p= 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively.


CONCLUSIONS
Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.
Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
Fuad
F
Hasan
Haifa
H
Asker
Jameela
J
Al-Khaldi
Iqbal
I
Siddique
Misfer
M
Al-Ajmi
Salim
S
Owaid
Rosh
R
Varghese
Basil
B
Al-Nakib
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011336:Probability; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b