Therapy in Acute Hepatitis C:
Relation to Hepatitis C Virus–
Speciﬁc T Cell Response Kinetics
Sanaa M. Kamal,
Camilla S. Graham,
Jens W. Rasenack,
Ahmed A. Tawil,
Jutta J. Fehr,
Khalifa El Sayed Khalifa,
Mahmoud M. Madwar,
and Margaret James Koziel
) improves sustained virological response rates in
chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its
action has been deﬁned. This prospective study assessed the efﬁcacy of PEG IFN-
in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-speciﬁc CD4
responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who
received either PEG IFN-
plus ribavirin (n ؍ 20) or PEG IFN-
monotherapy (n ؍ 20) for
24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively
followed. Serum HCV RNA,
T cell responses, and cytokine production
were measured before and during therapy and at follow-up and correlated to the outcome.
The sustained virological response rate was 85% with PEG IFN-
and 80% with PEG IFN-
monotherapy. Five untreated subjects had spontaneous recovery.
The frequency, magnitude, and breadth of HCV-speciﬁc CD4
T helper 1 responses were
signiﬁcantly higher in treated subjects compared with untreated subjects with self-limited
disease or subjects with chronic evolution. The CD4
T cell responses were maintained in
subjects with sustained virological responses and self-limited disease but ﬂuctuated in those
who developed chronic infection. In conclusion, PEG IFN-
therapy in acute hepatitis
induces high rates of sustained virological response and prevents choronicity, probably
through efﬁcient early stimulation of multispeciﬁc HCV-speciﬁc CD4
T helper 1 re
epatitis C virus (HCV) is an important public
health issue that affects 170 –200 million peo-
Acute HCV is usually asymp-
tomatic and therefore rarely recognized. Approximately
70% of infected persons develop chronic hepatitis, and
between 20%–30% of infected persons may develop cir-
Several controlled and uncontrolled trials
using different doses and durations of conventional inter-
) monotherapy in acute HCV reported
viral clearance rates ranging between 37% and 100% in
–treated patients compared with only 12%–20%
of untreated subjects. Most of these studies were problem-
atic because of the small number of subjects, the diverse
enrollment criteria, the different types and doses of
, the differences in the deﬁnition of response, and
the duration of follow-up.
The lack of controls in some
studies renders the results of such trials difﬁcult to inter-
pret given that 14%– 40% of patients with acute hepatitis
C may resolve spontaneously.
) has recently replaced
formulations in treatment of chronic
hepatitis C because of the higher rate of virological re-
sponse induced by PEG IFN-
The overall sus-
tained virological response (SVR) rate in patients with
chronic hepatitis due to genotype 2 and 3 reaches 85%;
Abbreviations: PEG IFN-
, pegylated interferon
; HCV, hepatitis C virus;
; SVR, sustained virological response; ALT, alanine amino-
transferase; PBMCs, peripheral blood mononuclear cells; ELISpot, enzyme-linked
immunosorbent spot; SI, stimulation index; IFN-
, IL-4, interleukin
4; SFCs, spot-forming cells.
Department of Infectious Diseases, Beth Israel Deaconess Medical
Center and Harvard Medical School, Boston, MA; the
Department of Internal
Medicine II, Gastroenterology and Hepatology, University of Freiburg, Germany;
and the Departments of
Gastroenterology and Liver Diseases and
Shams Faculty of Medicine, Cairo, Egypt.
Received November 19, 2003; accepted April 5, 2004.
Supported by grants from the National Institutes of Allergy and Infectious Dis-
eases (R21 AI054887 to S.M.K; R29 AI41563 to M.J.K), the International Society
of Infectious Diseases (S.M.K), and the Deutscheforschungsgemeinshaft (J.W.R.).
Address reprint requests to: Dr. Sanaa M. Kamal, Department of Infectious
Diseases, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115.
E-mail: Sanaa.Kamal@link.net; fax: 617-784-6989.
Copyright © 2004 by the American Association for the Study of Liver Diseases.
Published online in Wiley InterScience (www.interscience.wiley.com).