S. Kamal, Q. He, A. Al Tawil, K. Khalifa,
S. Hakam, W.
Saleh, M. Omar, J. Rasenack, M.
Koziel, M. Madwar
Background
The role, onset
and duration of peginterferon treatment have not been evaluated in acute
hepatitis C.
Objective
To assess
the efficacy, safety, onset and duration of peginterferon alfa (PEG IFN) in acute hepatitis C.
Methods
In this intent
to treat study patients with acute HCV genotypes 1 and 4 (n=98) were enrolled
and prospectively followed. Patients were screened for 8 weeks after
seroconversion or first positive PCR. Fifteen subjects refused treatment but
were followed through the study. Patients without spontaneous recovery were
randomized to begin PEG IFN-alpha monotherapy at wks 8, 12, 20 respectively for
either 12 or 24 weeks. A subset of subjects who failed to achieve a virologic
response after 12 wks of treatment continued therapy for additional 12 wks.
Results
Five
untreated subjects had spontaneous recovery and another 4 subjects scheduled to
start treatment at weeks 12 or 20 resolved spontaneously before therapy. 79
subjects with persistent viremia were randomized to 3 groups (Table). The end
of treatment response was 94% and the overall SVR was 82%. The SVR was better
for genotype 4 compared to genotype 1. Earlier treatment (week 8 or 12) was
associated with higher SVR particularly in genotype 1. Twelve week therapy was
sufficient for genotype 4 while higher SVR rates in genotype 1 patients were
achieved with 24 wks treatment (86%). Peginterferon alfa-2b monotherapy was
well tolerated and associated with significant improvement in the quality of
life.
Conclusion
Peginterferon
alfa-2b monotherapy improves sustained virologic response for acute hepatitis C
virus with genotype 1 and 4 infection. Earlier treatment leads to increased
virologic response. HCV genotype 1 may
require longer treatment duration.
S. Pol, F. Carrat, F.
Bani-Sadr, E. Rosenthal, F. Lunel, P.
Morand, D. Salmon, G. Pialoux, P.
Cacoub, C. Perronne ANRS
HC02-RIBAVIC Group
Background
Hepatitis
C may be severe in HIV-infected subjects evidencing the need to treat.
Aim
To compare
the safety and efficacy of the standard (IFNa2b: 3 MIU x3/w, n=207) (INF group)
to the pegylated (PEG-IFNa2b: 1.5 mg/kg x1/w, n=205) interferon (PEG group)
both combined with ribavirin (800mg/d, approx. 12 mg/kg/d) during 48 weeks.
Methods
A
randomized, multicenter, parallel-group, open-label trial. Inclusion criteria
were: HCV-RNA positive and abnormal liver histology, CD4>200, stable
HIV-RNA, off or stable HAART.
Results
The 412
patients (40 y, 74%M, 79% IVDU) were given HAART in 82%. Mean CD4 cell count was
514 ± 229/ml, HIV RNA<400 in 66% (mean HIV load in others: 3.7±0.7 logs).
The mean pre-treatment Metavir score was A 1.8±0.7, F 2.3 ± 1.0 and 39% of pts
had F3-F4 of which 17% had sustained normal ALT. Baseline variables were not
different between groups. Treatment discontinuation occurred in 167 pts (42%)
(86 IFN & 81 PEG) and severe adverse events in 127 (31%) (64 IFN & 63
PEG), including 6 mitochondriopathies. SVR was achieved in 20% of IFN pts vs
27% of PEG pts (p=0.047). In those who did not discontinue treatment,
virological response rates were at W4 (12 vs 20%), W12 (34 vs 41%), W24 (41 vs
54%), (W48: 34 vs 52%) and W72 (6 vs 35%), respectively. Virologic response at
W12 predicted SVR with 87% Positive Predictive Value and its absence had a 99% Negative
Predictive Value. SVR varied with genotypes 1 or 4 (11%) vs 3 or others (43%),
but not with the Metavir score or the adjusted ribavirin dose.
Response-associated pretreatment characteristics included genotypes other than
1 or 4 (OR=5.9), no protease-inhibitor therapy (OR=2.0), age = 40 years
(OR=1.9) and elevated ALT (OR=1.8). Necro-inflammation significantly decreased
in the PEG pts (-0.20 vs 0.02, p=0.0008). Fibrosis stabilized in virological
responders and worsened in non responders. Steatosis improved significantly in
patients infected by genotype 3 who had a SVR (p= 0.017).
Conclusion
In HIV-HCV
coinfected pts, the combination of pegylated IFNa2b and ribavirin is associated
with a superior HCV virologic response than standard combination with a quite
similar adverse-event profile.
K. Wursthorn, P. Buggisch, B.
Zoellner, M. Zankel, C. Fischer, S.
Xiong, C. Brosgart, G. Currie, J. Petersen
Background
HBV
targeted antiviral therapy with adefovir dipivoxil (ADV) results in a significant
reduction of intrahepatic HBV cccDNA, serum HBsAg, and serum HBV DNA
(Werle-Lapostolle, Gastroenterology 2004). Pegylated interferon alfa (Peg IFN)
improves serological outcome in HBeAg positive and HBeAg negative patients
(Lau, AASLD 2004; Marcellin, New Engl J Med 2004).
Aim
The aim of
this study was to determine the virological and serological outcome in patients
with chronic Hepatitis B treated with combination therapy of Peg IFN alfa 2b
and ADV.
Methods
26
patients with chronic Hepatitis B were included in a single center open label
pilot study. Patients received a 48 week course of antiviral combination
therapy with 12kDa pegylated interferon alfa 2b 1.5µg/kg bw qw and ADV 10mg qd.
23/26 patients were analyzed at the time of abstract submission, final data
will be available as of December 2004.
Intrahepatocellular cccDNA, serum HBsAg, and serum HBV DNA was
quantified as described previously (Werle-Lapostolle, Gastroenterology 2004).
Baseline characteristics:
Median age, years 33
Male 14
Caucasian 21
Asian
5
HBeAg + 15
HBeAg – 11
HBV DNA, PCR 5
x 106
(log10 copies/ml, median)
ALT (xULN, median) 3,1
Results
At week 48, compared to week 0:
cccDNA reduction (median, paired biopsies)
-2.2log
Serum HBsAg titer reduction (median) -44%
Serum HBV DNA reduction (median) -4.7log
Serum HBV DNA <100 copies/ml 12/23(52%)
(LLoD, LightCycler, Roche)
HBeAg loss 7/13
(54%)
HBeAg seroconversion 5/13
(38%)
HBsAg seroconversion 4/23
(17%)
ALT normalisation 10/23
(43%)
ALT improvement 19/23
(83%)