Pegylated Interferon Alpha-2b Plus Ribavirin in
Patients with Genotype 4 Chronic Hepatitis C: The
Role of Rapid and Early Virologic Response
Sanaa M. Kamal,
Samer S. El Kamary,
Michelle D. Shardell,
Imad N. Ahmed,
Sarah Abdel Hakem,
and Mohamed Abdelaziz
In patients chronically infected with hepatitis C virus (HCV) genotype 4, the optimum duration of
therapy and the predictors of sustained virologic response (SVR) have not been adequately deter-
mined. In this study, 358 patients with chronic hepatitis C genotype 4 were randomly assigned to
pegylated interferon (PEG-IFN) alpha-2b (1.5
g/kg/week) plus oral ribavirin (10.6 mg/kg/day) for
a ﬁxed duration of 48 weeks (control group, n ؍ 50) or for a variable duration (n ؍ 318). In the
variable-duration group, patients with undetectable HCV RNA at week 4 were treated for 24 weeks
(group A, n ؍ 69), patients with undetectable HCV RNA at week 12 were treated for 36 weeks (group
B, n ؍ 79), and the rest of the patients were treated for 48 weeks (group C, n ؍ 160). The primary
endpoint was SVR (undetectable HCV RNA 24 weeks after treatment cessation). Groups A-C and the
control group had SVR rates of 86%, 76%, 56%, and 58%, respectively. After the study was controlled
for predictors, a low baseline histologic grade and stage were associated with SVR (P < 0.029) in all
groups. In addition, among patients in group C, older age (P ؍ 0.04), a higher baseline body mass
index (P ؍ 0.013), and low baseline HCV RNA (P < 0.001) were also associated with SVR attain-
ment. The incidence of adverse events and the rate of discontinuation were higher in patients in the
variable-duration and ﬁxed-duration groups treated for 48 weeks. Conclusion: In patients with
chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12, treatment with
PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks, respectively, is sufﬁcient.
epatitis C virus (HCV) genotype 4 is the most
frequent cause of chronic hepatitis C in the
Middle East, North Africa, and sub-Saharan Af-
In countries such as Egypt, more than 90% of cases
of chronic hepatitis C are caused by HCV genotype 4.
Furthermore, recent epidemiological reports indicate that
HCV genotype 4 is beginning to spread from its native
African and Middle Eastern origins into countries of
Southern Europe such as France, Italy, and Spain and in
some foci in the United States, particularly among intra-
venous drug users.
Genotype 4 is the least studied of the HCV variants
and until recently has been considered difﬁcult to treat
because conventional interferon monotherapy has re-
sulted in disappointing virologic responses.
ever, recent reports show that a combination therapy
with pegylated interferon (PEG-IFN) alpha and riba-
virin markedly improves treatment outcomes, resulting
in a sustained virologic response (SVR) in 44%-69% of
However, determining the optimal treatment
duration is crucial for the minimization of unnecessary
or prolonged therapy and for the maximization of the
cost effectiveness of therapy. In addition, little is
known about predictors of response within popula-
tions infected with genotype 4; therefore, a tailored
approach to treatment, which has proved successful in
other HCV genotypes, remains elusive because of a
lack of reliable data.
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspar-
tate aminotransferase; BMI, body mass index; CI, conﬁdence interval; EOT, end-
of-treatment; EVR, early virologic response; HCV, hepatitis C virus; NPV, negative
predictive value; OR, odds ratio; PEG-IFN, pegylated interferon; PPV, positive
predictive value; RBV, ribavirin; RVR, rapid virologic response; SD, standard
deviation; SVR, sustained virologic response.
Department of Gastroenterology and Hepatology, Ain Shams Univer
sity, Cairo, Egypt;
Department of Epidemiology and Preventive Medicine, Uni
versity of Maryland School of Medicine, Baltimore, MD; and
Research Institute, DIAGSERA, Cairo, Egypt.
Received May 29, 2007; accepted July 9, 2007.
Supported by Schering-Plough (Kenilworth, NJ), Trans-European mobility scheme for
university studies (TEMPUS) (grant IMG 04-E.G-1096), and the International Society of
Infectious Diseases (United States; grant 9641).
The protocol registration was NCT00277862.
Drs. Kamal and Ahmed are currently afﬁliated with Beth Israel Deaconess Med-
ical Center, Boston, MA.
Address reprint requests to: Sanaa M. Kamal, Beth Israel Deaconess Medical Center,
110 Franas Street, Suite 2F, Boston, MA 02215. E-mail: firstname.lastname@example.org.
Copyright © 2007 by the American Association for the Study of Liver Diseases.
Published online in Wiley InterScience (www.interscience.wiley.com).
Potential conﬂict of interest: Drs. Sayed, Abdelaziz, Mansour, Moniem, Ibrahiem,
Hakem, Hashem, Kamal, and Muhammadi received grants from Schering-Plough.