Duration of Peginterferon Therapy in Acute
Hepatitis C: A Randomized Trial
Sanaa M. Kamal,
Khairy N. Moustafa,
Azza Abdel Moneim,
Khalifa E. Khalifa,
Leila A. El Gohary,
Amr H. Ramy,
Mohamed A. Madwar, Jens Rasenack,
and Nezam H. Afdhal
Spontaneous resolution of acute hepatitis C virus infection cannot be predicted, and chronic
evolution of the disease occurs in a majority of cases. To assess the efﬁcacy and safety of
peginterferon alpha-2b administered for 8, 12, or 24 weeks in patients with acute hepatitis
C virus infection a total of 161 patients were identiﬁed with acute hepatitis C virus infection.
Of these, 30 patients refused treatment but were retained in the study as a nonrandomized
comparison group. Of the 131 patients who consented to treatment, 29 patients spontane-
ously resolved, leaving 102 patients randomly assigned to peginterferon alpha-2b (1.5
kg) for 8 weeks (group A; n ؍ 34), 12 weeks (group B; n ؍ 34), and 24 weeks (group C; n ؍
34). The primary end point was sustained virologic response. An intent-to-treat analysis was
used for efﬁcacy and safety end points. Sustained virologic response was achieved in 23/34
(67.6%), 28/34 (82.4%), and 31/34 (91.2%) of patients in groups A, B, and C, respectively;
all had undetectable hepatitis C virus RNA 48 weeks after the end of therapy. Treatment for
8 or 12 weeks was effective in genotypes 2, 3, and 4, whereas genotype 1 required 24 weeks
of therapy. The 8- and 12-week regimens were associated with fewer adverse events com-
pared with the 24-week regimen. In conclusion, peginterferon alpha-2b effectively induces
high sustained virologic response rates in patients with acute hepatitis C virus infection, thus
preventing development of chronic hepatitis C. Duration of treatment should be further
optimized based on genotype and rapid virologic response at week 4.
epatitis C virus (HCV) infects an estimated 170
to 200 million people worldwide, making this dis-
ease a clear and signiﬁcant public health issue.
Unfortunately for most people infected with HCV (70%-
85%), spontaneous resolution is uncommon. Almost 50%
to 60% of individuals with acute infection develop
chronic hepatitis that can lead to cirrhosis, hepatocellular
carcinoma, and a requirement for liver transplantation.
Treating individuals with acute HCV infection may
prevent development of chronic hepatitis. However, this
strategy may be limited by infrequent clinical diagnosis of
acute HCV infection.
Approximately 70% to 80% of
patients infected with acute HCV are asymptomatic, and
whereas 15% to 30% of patients develop symptomatic
acute hepatitis syndrome, this is generally mild.
clinical diagnoses of acute HCV infection are in individ-
uals who suspect they may have been exposed to the virus
as in healthcare workers who have received an accidental
needle-stick injury, injection-drug users or persons with
possible sexual transmission.
Several studies have shown that early treatment of
acute HCV infection with interferon monotherapy en-
hances the likelihood of virologic response, with viral
clearance rates ranging between 37% and 90%.
ever, these trials are difﬁcult to interpret given the diverse
enrollment criteria, the small number and heterogeneity
of participants, the lack of controls, the different types
and doses of interferon used, the differences in the deﬁni-
tion of response, and variation in duration of follow-up (4 to
48 weeks). Furthermore, acute HCV infection may resolve
spontaneously in 20% to 40% of patients.
Abbreviations: HCV: hepatitis C virus; SVR, sustained virologic response; ALT:
alanine aminotransferase; RVR: rapid virologic response.
Department of Gastroenterology and Liver Disease Center, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA;
Gastroenterology and Liver Diseases, Ain Shams University, Cairo, Egypt; and
Department of Gastroenterology and Liver Diseases, University of Freiburg,
Received January 4, 2006; accepted February 16, 2006.
NIH registration: trial ID number NCT00241618.
Address reprint requests to: Dr. Sanaa M. Kamal, Liver Disease Center, Beth
Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 02115.E-mail:
Sanaa.Kamal@link.net; fax: 617-249-0670.
Copyright © 2006 by the American Association for the Study of Liver Diseases.
Published online in Wiley InterScience (www.interscience.wiley.com).
Potential conﬂict of interest: Dr. Rasenack consults for, advises, and received
travel grants from Schering-Plough.