ORIGINAL ARTICLE
Induction therapy with twice-daily interferon-beta does not improve
the therapeutic efficacy of consensus interferon monotherapy forchronic hepatitis C
Hidetsugu Saito,1 Shinichiro Tada,1 Hirotoshi Ebinuma,1 Hiromasa Ishii,1Kazuo Kashiwazaki,2 Jiro Nishida,3 Takeshi Yoshida,4 Shigeyuki Zeki,5 Hideo Yoshida,6Masahiro Yoshioka,7 Yasutaka Inagaki,8 Naoki Kumagai,9 and Toshifumi Hibi1

Department of Internal Medicine, 1School of Medicine, Keio University, Tokyo; 2Tachikawa Hospital,
Tokyo; 3Tokyo Dental Collage Ichikawa General Hospital, Chiba; 4Saitama Social Insurance Hospital,
Saitama; 5Keiyu Hospital, Kanagawa; 6Eiju General Hospital, Tokyo; 7Minami-Tama Hospital, Tokyo;
8
Nihon Kohkan Hospital, Kanagawa; 9Kitasato Institute Hospital, Tokyo, Japan(Received for publication on February 13, 2006)(Revised for publication on July 14, 2006)(Accepted for publication on July 20, 2006)

Abstract. We examined therapeutic superiority of induction therapy with twice-daily IFNß (3X2=6 million units/day) onto 6-months consensus interferon monotherapy for chronic
hepatitis C. Patients were randomly assigned to monotherapy without (group I, n=16) andwith induction therapy (group II, n=12). The mean age of group II was older than that ofgroup I, and other baseline condition was not statistically significant. Sustained virologicalresponse (SVR) rates of group I and II were 81.3% (13/16) and 58.3% (7/12), respectively(p=0.365). SVR rates in patients with genotype 1b were 66.7% (4/6) and 0% (0/2, becauseof drop-out), and those with high viral load were 70% (7/10) and 75% (6/8) in group I and II,
respectively (p=1.000). Drop-out rates during therapy were 6.3% (1/16) and 33.3% (4/12) ingroup I and II, respectively (p=0.176). Age less than 50 years was the only independent factor that was shown by multivariate logistic model analysis to be associated with a sustained
virological response. Although randomization failed to produce and equal age distribution
in the two groups in this study, our results suggest that induction therapy with twice-daily
IFN- ß has no beneficial effect on the efficacy of monotherapy with consensus interferon,probably because of the higher drop-out rates and incidence of adverse reactions with induction therapy. (Keio J Med 55 (3): 111－117, September 2006)
Key words: consensus interferon, interferon-beta, induction therapy, monotherapy

Introduction
The worldwide prevalence of hepatitis C virus (HCV)
infection is estimated at 170 million people, and the natural history of this infectious disease involves progression to chronic liver failure or liver cirrhosis with complications such as hepatocellular carcinoma.1 Interferon(IFN) therapy has been approved for HCV treatment inJapan since 1993 and treatment has since been improvedby the development of several new types of IFN. Re-

cently, combination treatment with pegylated IFN (PegIFN) and ribavirin (RBV) for at least one year has been
recommended for patients with HCV genotype 1b and ahigh viral load (>100 KIU/mL).2 , 3 This group of patientsis thought to be difficult to treat; they show sustained
viral response (SVR) rates of less than 10% following
6-month IFN monotherapy, although this has recently
been improved to 50% with 1-year Peg-IFN plus RBV
combination therapy.
Consensus IFN (CIFN), also referred to as IFN al-

Reprint Requests to: Dr. Hidetsugu Saito, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo
160-8582 Japan, E-mail: hsaito@sc.itc.keio.ac.jp111

Saito H, et al: Consensus IFN monotherapy for chronic hepatitis C

112facon-1, is a recently developed recombinant form of
IFN. This type of recombinant IFN was produced byassigning the most frequently observed amino acid ineach position (consensus amino acid in a position) afterscanning the sequences of several known IFN-α subtypes.4 CIFN has demonstrated higher antiviral effects invitro and in vivo, and less adverse reactions in vivo thannatural IFN-α, recombinant IFN-α2a, or IFN-α2b.5 , 6 The
results of previous studies in Japan have demonstrated
that CIFN at a dose of 18 MU is effective and tolerable
in patients with chronic HCV and a high viral load.7
On the other hand, twice-daily IFN-β administration
was reported to result in a higher response rate thanonce-daily administration by compensating for the compounds short half-life. Several studies suggested that
IFN-β triggers biological responses distinct from thoseof IFN-α and through different downstream signals,
although the same receptor type should be utilized byboth IFN-α and-β. Twice-daily administration of IFN-β
decreases HCV RNA more than does once-daily dosing,
especially during the first 14 days of treatment.8 , 9
On the basis of these findings, we tested combination
treatment for chronic hepatitis C with CIFN and induction therapy with twice-daily IFN-β. We analyzed theefficacy and tolerability of this induction therapy in a
multicenter, randomized, open-trial.
Patients and Methods
Patients
This study was approved by the ethical committeeof the Keio University, School of Medicine, and the
University Hospital. The affiliated hospitals of Keio
University participated in this study, and the protocol
was approved by the ethical committee of each hospital. Patients with chronic hepatitis C who visited these
hospitals from March 2002 to September 2003 wereenrolled in this study. Patients having HCV RNA levels
more than 500 KIU/mL were excluded from the study,
because CIFN monotherapy has been reported to havelittle efficacy on this group of patients. Hepatitis B virus― and human immunodeficiency virus ― positive patients,
those whose daily alcohol consumption exceeded 60
g, and those with other types of liver diseases were excluded. Most patients received a liver needle biopsy before having treatment, and histological assessment was
performed according to the New Inuyama Classification,
which is a standard diagnostic criterion in Japan. HCVRNA levels were examined using an AmpiCor GTHCV Monitor Version 2.0 (Roche Molecular Systems,
Pleasanton, CA, USA) and HCV serotypes were examined by the enzyme immunoassay for HCV grouping.
Serum transaminase levels, blood cell counts, and otherbiochemical measurements were sequentially examined.

Adverse reactions were monitored by careful interview
and medical examination throughout the study. Because
fever and other influenza-like symptoms are frequentside effects, non-steroid anti-inflammatory drugs wereprescribed for all patients and were taken if the symptoms occurred.
Treatment
At the start of therapy, the Japanese Ministry of Laborand Welfare had only approved 6-month IFN therapy
for chronic hepatitis C, and Peg-IFN had been approved.
RBV was approved in December 2001. Patients having
HCV viremia and suffered from histologically provenchronic hepatitis C were enrolled. Informed consent ofparticipation to this study was obtained from each patientwith a written document and the signature. Thirteen hospitals, Keio University hospital (4), Tachikawa Hospital(5), TEPCO Hospital (4), Tokyo Dental Collage Ichikawa General Hospital (3), Eiju Hospital (2), Saitama
Social Institute Hospital (2), Minami-Tama Hospital (2),Fussa Hospital (1), Keiyu Hospital (1), Kitasato InstituteHospital (1), Nihon Kohkan Hospital (1), Tokyo Medical Center (1), Tokyo Metropolitan Ohtsuka Hospital(1) (The number of patients enrolled) were participatedin this study. Patients were randomly assigned to twotreatment groups; group I, receiving 18 MU/day CIFN
(Advaferon®, Amgen Inc. Thousand Oaks, CA, USA)subcutaneously daily for 2 weeks and three times a week
for 22 weeks, and group II, receiving 3 MU of twicedaily (totally 6 MU/day) IFN-β (Feron®, Toray, Tokyo,
Japan) intravenously for 2 weeks (induction) and then
18 MU/day CIFN three times a week for 22 weeks. Randomization was performed by an envelope methods. The
treatment protocol was decided after the enrollment was
assigned to the group at the central office of this study
located at the Keio University. The dose was reduced to
12 MU/day if side effects such as decreased blood cellcounts appeared. When side effect occurred during thefirst 2 weeks of treatment in group II, the dose of IFNβ was reduced to 3 MU once-daily. SVR was defined as
the absence of serum HCV RNA from the end of treatment until 6 months post-treatment. The treatment was
stopped when a patient declined having further treatment
because of adverse effects, such as high fever, itchy
eruption, severe fatigue, alopecia, and so on. When thephysician found severe adverse reactions, such as proteinuria, leucopenia (<2,000/mm3), low platelet counts(<50,000/mm3), elevation of ALT levels (>500 IU/L),
and depressive state, the treatment was stopped with anagreement.
Statistics
Treatment outcome was analyzed on an intention-to-Keio J Med 2006; 55 (3): 111－117

113

Table 1 Baseline distribution of various clinical factors of the patients
according to treatment regimens

Table 2 Sustained virological response rates and clinical factors
according to treatment groups

Baseline factor

p value

Factors

0.0128All cases

1.0000AgeGroup IAge (mean±SD)45.8±10.0aHabitual Drinkingb

11 (68.8%)

Group II56.2±10.3
8 (66.7%)aa0.66451.000072.7% (8/11)

50.0% (4/8)

0.5945

100% (5/5)

75.0% (3/4)

0.9056－

80.0% (8/10)

54.6% (6/11)

0.4399

＋83.3% (5/6)

100% (1/1)

1.0000－100% (9/9)

55/6% (5/9)

0.0890

＋57.1% (4/7)

66/7% (2/3)

1.00001b66/7% (4/6)

0% (0/2)

0.4142

90.0% (9/10)

66.7% (6/9)

0.4951

Genotypeb 1b

6 (37.5%)

2 (16.7%)

0.5149Gendera Male

10 (62.5%)

9 (75.0%)

HCV RNAb <100 KIU/mL≥100 KIU/mL

6 (37.5%)

4 (33.3%)

10 (62.5%)

FemaleDrinking habita1.00008 (66.7%)

Past IFN

GenotypeaLiver Histologyc
0.88900.365150% (4/8)

0.5312

1 (8.3%)

58.3% (7/12)
75.0% (3/4)

9 (75.0%)0

81.3% (13/16)

57.1% (4/7)

9 (56.3%)

Unknownp value

100% (9/9)

Past IFN therapy (＋)

2a/2bGroup II

<50
≥50

b

Group Ia

F stage F1

7 (58.4%)

6 (54.6%)

F2

4 (33.3%)

4 (36.4%)2a/2b

1 (9.0%)HCV RNA <100 KIU/mL 100% (6/6)

F3

1 (8.3%)25.0% (1/4)

0.067170% (7/10)

75.0% (6/8)

1.0000F stage F1

85.7% (6/7)

50.0% (3/6)

0.43061.0000a≥100 KIU/mL

Unknown

4

1

A grade A1

4 (33.3%)

4 (36.4%)

A2

7 (58.4%)

7 (63.4%)

A3

1 (8.3%)0F2100% (4/4)

75.0% (3/4)

4

1

F3

100% (1/1))

100% (1/1)

A gradeA1

100% (4/4)

3.3% (1/3)

0.27711.0000Unknown

0.9377

Biochemistrya (mean)

Liver histologyb

AST (IU/L)

59.6

70.3

0.4564A2

85.7% (6/7)

85.7% (6/7)

ALT (IU/L)

80.6

118.0

0.1337A3

100% (1/1)

0% (0/0)γGTP (IU/L)

62.8

51.4

0.5026

ALB (g/dL)

4.30

4.17

0.4275Hb (g/dL)

14.6

13.9

0.3301WBC (/µL)

5801

5785

0.9784

PLT (104/µL)

19.7

19.1

0.8055

ALB, albumin; PLT, platelet counts; a analyzed by t-test forcontinuous factors, banalyzed by Chi-square test for binary factors,canalyzed by Wilcoxon test for ordinal factors

treat basis and we also analyzed on a per-protocol basis.
Patients’ background was analyzed by Student t-test,
Wilcoxon test, and chi-square test. Differences in efficacy, adverse reactions, and other parameters between
treatment groups were analyzed by Fisher’s exact test,
Mann-Whitney U test and chi-square test. Predictive factors for obtaining SVR were analyzed using a logistic
model among factors such as treatment regimen (group
I or II), age (<50 or ≥50), gender (male or female),habitual alcohol consumption (+ or -), HCV genotype(1b or 2a/2b), baseline viral load (<100 KIU/mL or ≥100 KIU/Ml), F stage (F1 or F2/3), and A grade (A1 or
A2/3).

Statistical analysis was performed by aChi-square test, bWilcoxon testfor ordinal factors.

Results
Patient backgrounds
The comparison of patient backgrounds is shown in
Table 1. No statistical difference was found in gender,
past blood transfusion, alcohol consumption, past IFN
treatment, HCV genotypes, HCV RNA levels, liver
histology, basal transaminase levels, other biochemicalparameters, blood cell counts, positivity of anti-nuclear
antibody, immunoglobulin levels, urine protein, andurine glucose. Age was the only factor that differed significantly; the mean age was greater in group II than ingroup I (56.2 vs 45.8 year old, p=0.013).
Virological response
SVR was achieved in 13 of 16 (81.3%) and 7 of 12(58.3%) patients in Group I and II, respectively (p=NS).
Serum HCV RNA disappeared 4 weeks after the start ofSaito H, et al: Consensus IFN monotherapy for chronic hepatitis C

114
Table 3 Sustained biochemical response rates and clinical factors
according to treatment groups
Factors

Group IGroup IIp value

All casesa

68.8% (11/16)

58.3% (7/12)

0.8644<50

100% (9/9)

50.0% (2/4)

0.1407≥50

57.1% (2/7)

50% (5/8)

0.4264

Gendera Male

63.6% (7/11)

62.5% (5/8)

1.000080.0% (4/5)

50.0% (2/4)

0.8125－70.0% (7/10)

54.5% (6/11)

0.7806＋

66.7% (4/6)

100% (1/1)

1.0000－77.8% (7/9)

55/6% (5/9)

0.6171＋

57.1% (4/7)

66/7% (2/3)

1.00001b83.3% (5/6)

0% (0/2)

0.67332a/2b80.0% (8/10)

33.3% (3/9)

0.8908HCV RNA <100 KIU/mL 83.3% (5/6)

Agea

FemaleDrinking habitaPast IFNa

Genotypea

100% (4/4)

1.000060% (6/10)

37.5% (3/8)

0.6353F stage F1

85.7% (6/7)

66.7% (4/6)

0.8789F2

75.0% (3/4)

75.0% (3/4)

1.0000F3

100% (1/1))

0% (0/1)

A gradeA1

100% (4/4)

100% (3/3)

A2

71.4% (5/7)

57.1% (4/7)

A3100% (1/1)

0% (0/0)a≥100 KIU/mL
Liver histologyb

1.0000Statistical analysis was performed by aChi-square test, bWilcoxon testfor ordinal factors

therapy in 91.7% and 71.4% of patients in group I andII, respectively (p=NS). Several factors were analyzed inrelation to treatment efficacy, and no significant difference in SVR rates between the two treatment regimens
were found for any of these factors (Table 2). SVR was
achieved in 6 of 6 (100%) patients with low HCV RNA
levels (<100 KIU/mL) in group I, and only one patient
was over 50 year old in 6 patients with low viral load(<100 KIU/mL). This one patient obtained SVR. On
the other hand, all the 4 patients in the induction group(group II) having low viral load were over 50 year old,and only 1 of 4 (25%) in group II (p=NS) responded. In
patients with genotype 2 (2a/2b), the response rate washigh, and SVR was achieved in 9 of 10 (90.0%) and 6 of
9 (66.7%) patients in group I and II, respectively. SVR
rates of patients with high viral load (>100 KIU/mL)
were 70.0% (7/10) and 75.0% (6/8) in group I and II,
respectively (p=NS). In patients with HCV genotype
1b, the response rate was 66.7% (4/6) in group I, and 2
patients in group II dropped out because of adverse reac-

Fig. 1 Serum transaminase levels before, during, and after thetherapy. Serum transaminase (AST and ALT) levels before, during and after treatment are shown sequentially according to treatment groups. The solid line indicates levels in group I and thedotted line indicates levels in group II. Asterisks indicate time
points for which statistical significance (p<0.05) was found. Statistical significance was analyzed using student t-test by time.

tions. In difficult-to-treat patients who had genotype 1band high viral loads, SVR was obtained in 1 of 5 (20.0%)
patients in group I and 0 of 2 (0%) in group II.
We found the same result of this intention-to-treat
analysis with per-protocol analysis. SVR was achievedin 13 of 15 (86.7%) and 5 of 8 (62.5%) patients in GroupI and II, respectively (NS). All patients under 50 year
old (n=9 and 2 in group I and II, respectively) well responded to the therapy and obtained SVR, even in patients with genotype 1b (3 patients in group I). SVR was
achieved in 7 of 12 patients over 50-year-old (6 in group
I and 6 in group II). In group I, 4 of 6 patients (66.7%)
obtained SVR and 3 of 6 patients (50%) obtained ingroup II.
Biochemical respones
Sustained biochemical response (SBR; serum transaminase levels are stable within normal range for morethan 6 months after the end of therapy) was achieved inKeio J Med 2006; 55 (3): 111－117

115

Table 4 Contributing factors for achieving sustained virological response by multivariate analysis

Table 5 Adverse reactions
ReactionGroup IGroup II

Factors

Odds ratio

95% C.I.

p value

General fatigue

4

3 (1)

Regimen group I

6.62

0.49－393.13

0.136

Fever

3

4

Decrease in WBC

31

Eruption

2 (1)

2 (1)

Swelling of injection site

0

3 (1)

Depression

0

2 (1)

Proteinurea

01

Alopecia01group II

1.00

<50

14.99

≥50

1.00

HCV genotype 1b

0.08

Age

2a/2b

0.98－1175.62

0.028

0.00－1.41

0.098

1.00

Statistical analysis was performed by logistic regression analysis using
exact estimation.

Values in parentheses indicates the number of patients who stopped
treatment because of side effects.; WBC, white blood cell counts

11 of 16 (68.8%) and 7 of 12 (58.3%) patients in group
I and II, respectively (p=NS). There were no significant
differences in SBR rates between treatment regimens
for any of the clinical factors (Table 3). Serum transaminase levels (aspartate aminotransferase, AST; alanine
aminotransferase, ALT) were monitored every 4 weeks
until 24 weeks after cessation of therapy. Transaminase
levels in group II patients were always higher than thoseof group I patients during treatment (Fig. 1) ALT levels
at 12 weeks and AST levels at 8, 12 and 16 weeks weresignificantly higher in group II than in group I. These
differences no longer existed after cessation of treatment.
Logistic regression analysis
Only age (p=0.038) was found to be a significant predictive factor for achieving SVR between these factors
by univariate analysis. The predictive factor was also analyzed with “per-protocol” basis, and only age (p=0.037)
was found to be significant.
To determine which factor contributed to obtaining SVR, a multivariate logistic model analysis was
performed among regimen, age and HCV genotype,because regimen and HCV genotype were factors withp-values less than <0.1 in the univariate analysis (Table4). Only age was found to be statistically significant,and the odds ratio for younger patients (<50-year-old)was 2.71 (95% C.I. 0.98-1175.62). This factor, age, wassimilarly pointed-out when per-protocol analysis was applied (p=0.046).
Adverse reactions
Adverse reactions appeared in 9 of 16 (55.3%) and
12 of 12 (100%) patients in group I and II, respectively(Table 5). Treatment was discontinued in only 1 of 16(6.3%) patients in group I and 4 of 12 (33.3%) in group

II (p=NS) because of adverse reactions. Moderate decrease in blood cell counts was observed in 4 cases, andtreatment was discontinued in 1 case. All side effects
abated after cessation of therapy. One patient in group
II dropped out because of eruption during the first two
weeks when IFN-β was administered. Other three patients in group II dropped out after two weeks when
CIFN was administered. Leukopenia, decrease in platelet counts, retinopathy and proteinuria have been more
frequently reported in IFN-β treatment than in IFN-α
treatment, but no patient dropped out by these side effects in this study.
Discussion
In the present study, we examined IFN monotherapy
for 6 months, which was the standard therapy in Japan
until December 2001. RBV, which is always administered with IFN, is a nucleoside analogue that facilitates
the anti-viral efficacy of IFN, and was approved in
December 2001 by the Japanese Ministry. Since then,IFN-α2b plus RBV combination therapy for 6 months
became the standard therapy for difficult-to-treat patients.1 0 At that time, the duration of IFN monotherapy
was limited to 6 months, and the SVR rates reported indifficult-to-treat patients were less than 10%, and the
SVR rates in low viral load (less than 100 KIU/mL) or
genotype 2a/2b patients were 50 to 70%. Many studies
including the present one have reported alternative treatments involving the addition of other agents or different
IFN doses within 6 months. 1 1- 1 3 The SVR rate in ourstudy was similar to those obtained in previous studies.
CIFN was developed through recombinant technology
and was expected to be more effective than other agentsfor chronic hepatitis C. Several reports demonstrated
greater efficacy of CIFN as compared with other typesof IFN, such as natural IFN (7), IFN-α2a or α2b.1 4 It

116

appears that the frequency of adverse reactions with
CIFN is less than that with other IFNs, so CIFN can beused at a higher dose in patients with chronic hepatitis
C.15 , 16 The standard dose of CIFN was set at 18 MU/day,a dose which is not tolerable with other types of IFN.
Sjögren et al.1 7 demonstrated that the combination of
CIFN and RBV provided better response compared withthe combination of IFN-α2b and RBV in patients infected with genotype 1 and a high viral load. In the present
study, 18 MU/day of CIFN was also well tolerated andinduction therapy with twice-daily IFN-β tended to beless tolerable. No significant reason other than a bias ofaged patients has been found why the number of dropped
out patients in group II was larger than that in group I.
Induction therapy with daily CIFN until the disappearance of HCV RNA was reported to be effective ineliminating HCV RNA at 12 weeks but the final SVR
rate was not superior to treatment without induction
therapy. Induction therapy always decreases serum HCV
RNA more rapidly than does ordinal therapy, however
Layden and colleagues1 8 reported that induction therapy
with CIFN did not increase SVR rates as comparedwith therapy without induction. Zeuzem 1 9 suggested
the likelihood that SVR rates would be increased byinduction therapy for more than 2 weeks, however Pockros 2 0 demonstrated that daily dosing of CIFN might
be difficult to tolerate, resulting in discontinuation oftherapy in a significant proportion of patients. These
results suggest that induction therapy with CIFN is noteffective in increasing response rates. Hirashima andassociates 2 1 used a combination of lactoferrin with
CIFN therapy, and found no additive effect. However,Zeuzem,1 9 still recommended additional induction-type
studies focused on naïve difficult-to-treat patients and on
previous non-responders, even after the introduction of
Peg-IFN. We investigated the effect of induction therapy
with twice-daily IFN-β on CIFN treatment in this study.
Induction therapy with twice-daily IFN-β hasb e e n s h o w n t o i m p r o v e t h e e f f i c a c y o f I F N -α
monotherapy,2 2-2 4 although response rates for patientswith both genotype 1b and a high titer of HCV RNA
were low. Although Suzuki and colleagues 2 5 reported
that twice-daily administration was not superior toa once-daily regimen for patients with genotype 1band high HCV RNA levels, twice-daily therapy didchanges HCV dynamics in the early phase of IFN-α
monotherapy 2 6 and IFN-α2b plus RBV combination
therapy. 8 We compared CIFN monotherapy regimens
with and without induction therapy with twice-daily
IFN-β. SVR rates of the induction therapy group weresimilar with those of CIFN monotherapy group, and nobeneficial effect of the induction therapy was found evenin patients with genotype 2a/2b. Therefore, the results ofthis study lead us to conclude that induction therapy with
IFN-β did not improve the therapeutic efficacy of CIFN

Saito H, et al: Consensus IFN monotherapy for chronic hepatitis C

monotherapy for chronic hepatitis C.
Normalization of serum transaminase levels is a good
prognostic factor in patients with chronic hepatitis C, but
induction therapy did not always decrease transaminase
levels in this study. After cessation of therapy, serumtransaminase levels normalized in the same proportionof patients in both treatment groups, since SBR rates of
the groups were similar. The levels during treatment,
however, were always higher in patients of group II thanin those of group I, indicating that induction therapy
was not superior for stabilizing hepatic injury. The elevation of serum ALT levels during IFN-β therapy has
been reported previously and did not seem to result fromincreased hepatitis activity,2 7 but the elevation of transaminase levels during treatment may have no beneficial
effect on liver function, if good biochemical and virological responses could be obtained thereafter.
There are some limitations to this study. One is thatthe mean age of patients in the induction group was
significantly older than that of patients without induction therapy, even though the patients were randomly
assigned. This confounding due to age for the induction group was one of reasons why the IFN-β induction
was not effective in this study. Failure of randomizationand higher truncation of treatment during the treatment
period could lead to underestimation of efficacy of the
IFN-β induction therapy. On the contrary, CIFN exerts strong antiviral effect on HCV infection, and daily
CIFN administration showed similar antiviral effectwith twice-daily IFN-β administration as for negative
rate for HCV at the first 2 weeks. In this study, negative
rate at the first 4 weeks was 85.7% and 63.6% (p=NS)
in CIFN group and IFN-β induction group, respectively.
Therefore, it is also considered that antiviral effect of
the IFN-β induction does not superior to the daily CIFN
administration. There must be enough number of subjects to avoid having larger random variation of outcome
indices. However, the number of patients enrolled in thistrial was small. Enrollment of many more patients might
have overcome this limitation, but we found it difficult
to recruit additional patients, since the use of RBV wasapproved at the same time with this study, and IFN-α
2b plus RBV combination therapy was indicated forthe same group of patients participating in this study. It
was already known that IFN-α2b plus RBV combination therapy achieves much more SVR rates than IFNmonotherapy even the induction therapy was introduced.
Therefore, patients with chronic hepatitis C easily refused our offer to participate in this study at that time.
In conclusion, our results suggest that induction therapy
with twice-daily IFN−β is not much superior to the therapeutic efficacy of CIFN monotherapy, and a large study
may clarify whether the induction therapy improves efficacy.

Keio J Med 2006; 55 (3): 111－117
Acknowledgment: This study was conducted among Department ofInternal Medicine of Keio affiliated hospitals; Keio University Hospital,
Eiju General Hospital, Fussa Hospital, Kawasaki City Kawasaki
Hospital, Keiyu Hospital, Kitasato Institute Hospital, Minami-Tama
Hospital, National Saitama Hospital, Nihon Kohkan Hospital, Saitama
Social Insurance Hospital, Tachikawa Hospital, TEPCO Hospital,
Tokyo Dental Collage Ichikawa General Hospital, Tokyo Medical
Center, Yokohama City Hospital, Tokyo Metropolitan Hiroo Hospital,
Tokyo Metropolitan Ohtsuka Hospital, and Metropolitan Saisei-Kai
Central Hospital, Tokyo.

117

12.

13.

14.

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