The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients.

Abstract

The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response.
There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001).
The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.

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RESEARCH ARTICLEOpen Access
The effect of pegylated interferon-alpha2b and
ribavirin combination therapy for chronic
hepatitis C infection in elderly patients
Hiroki Nishikawa1,2*, Eriko Iguchi1, Yorimitsu Koshikawa1, Soichiro Ako1, Tadashi Inuzuka1, Haruhiko Takeda1,
Jun Nakajima1, Fumihiro Matsuda1, Azusa Sakamoto1, Sinichiro Henmi1, Keiichi Hatamaru1, Tetsuro Ishikawa1,
Sumio Saito1, Ryuichi Kita1, Toru Kimura1and Yukio Osaki1
Abstract
Background: The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence
of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports
concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly
patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus
ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of
sustained virological response–defined as the absence of detectable hepatitis C virus in serum 24 weeks after the
treatment ended–and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108
elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response.
Results: There was no significant difference in the sustained virological response rate between younger patients
and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype
1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant
difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108),
respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing
significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet
count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4
or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response
was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001).
Conclusions: The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly
patients are not always inferior to those in younger patients. Obtaining an early virological response may be
essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.
Keywords: Chronic hepatitis C, Pegylated interferon, Ribavirin, Treatment response, Elderly patients
Background
Chronic hepatitis C virus (HCV) infection affects
approximately 300 million people worldwide and is the
most common cause of chronic liver disease [1]. Among
HCV-infected individuals, 20-30% eventually develop
cirrhosis or hepatocellular carcinoma (HCC). In Japan,
approximately 30,000 people die of HCC every year, and
70-80% of these deaths are because of HCV infection.
Therefore, it is important to eliminate HCV with inter-
feron (IFN) therapy to prevent HCC [2,3].
Hepatitis C virus entered and expanded in Japan dec-
ades before it did so in the United States [4]. In Japan,
the patients with chronic HCV who are currently treated
with IFN are 10 to 15 years older than the corresponding
patients in the United States and Western countries,
* Correspondence: h-nishikawa@osaka-med.jrc.or.jp
1Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital,
Osaka, Japan
Full list of author information is available at the end of the article
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© 2012 Nishikawa et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

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where the patients treated with antiviral therapy average
45 years of age.
In Japan, HCV infection is characterized by an increas-
ing prevalence with age [5]. Previous studies have
reported that clearance of HCV by IFN therapy signifi-
cantly reduces the incidence of HCC and death in older
chronic hepatitis patients [3]. Therefore, it is particularly
important to eliminate HCV in elderly patients.
The standard treatment for patients chronically infected
with HCV is pegylated interferon (Peg-IFN) and ribavirin
combination therapy for 24 or 48 weeks, according to the
HCV genotype [6]. This treatment protocol reportedly
obtained sustained virological response (SVR) rates-
defined as undetectable HCV in serum 24 weeks after the
treatment ended–ranging from 45% in patients with HCV
genotype 1 to 85% in patients with genotypes 2 or 3 [7,8].
Recently, the addition of a protease inhibitor to Peg-IFN
plus ribavirin combination therapy (triple therapy) has
been reported to improve the anti-viral effect [9]. How-
ever, these figures were obtained in patients aged 40 to 50
years, as older patients have been excluded from large
therapeutic trials [7-9]. Therefore, to date, there are few
data concerning the response and safety of this combina-
tion treatment in elderly patients [10-12].
The aims of the present study were to examine the
effect and safety of Peg-IFN-alpha2b and ribavirin combi-
nation therapy in elderly patients and to examine the fac-
tors contributing to the SVR in this combination therapy.
Methods
Patients
Between January 2005 and April 2008, 427 consecutive
patients with chronic hepatitis C were treated with Peg-
IFN-alpha2b and ribavirin combination therapy at the
Department of Gastroenterology and Hepatology, Osaka
Red Cross Hospital, Japan. Each patient was followed up
for at least 24 weeks after the treatment ended. Of the
427 patients, 319 were < 65 year old (younger patients)
and 108 were ≥ 65 years old (elderly patients). Whether
the patients were treated with this combination therapy
was mainly based on the decisions of their attending phy-
sicians, considering factors such as age, motivation for
the combination therapy, general condition, and underly-
ing diseases. Treatment of chronic HCV with a combina-
tion of Peg-IFN-alpha2b and ribavirin was approved by
the Japanese Ministry of Health in October, 2004. How-
ever, the use of PEG-IFN-alpha2a and ribavirin was only
approved in September, 2008. Therefore, in the present
study, all patients were treated with PEG-IFN-alpha2b
and ribavirin combination therapy.
We analyzed the clinical data retrospectively. Patients
were excluded if they tested positive for human immuno-
deficiency virus infection, or if they had decompensated
liver disease, liver disease of other cause, psychiatric
illness, severe cardiovascular disease, autoimmune dis-
ease, poorly controlled diabetes mellitus, renal disease, or
alcohol abuse. A liver biopsy was performed in all
patients before the treatment, and all biopsy specimens
were assigned a fibrosis score and an activity score based
on the criteria of Bedossa et al. [13]. This study was con-
ducted according to the ethical guidelines of the 1975
Declaration of Helsinki, and informed consent was
obtained from all patients. We received ethical approval
for the present study from the ethics committee of our
hospital, Osaka Red Cross Hospital, Japan.
Treatment schedule
Patients were treated with Peg-IFN-alpha2b (1.5 μg/kg/
week) plus oral ribavirin according to the Japanese guide-
lines (total dose 600 mg/day for patients weighing < 60
kg; 800 mg/day for patients with a body weight of 60-80
kg; 1,000 mg/day for patients weighing > 80 kg). Treat-
ment was given for 48 weeks for genotype 1 and 24
weeks for genotype 2. If hematologic side effects were
observed, the doses were reduced according to informa-
tion from the manufacturer. However, in the case of side
effects associated with subjective symptoms of Grade 2 or
above, such as malaise, fever, anorexia, or light-headed-
ness, the dose of Peg-IFN was reduced by 10-20 μg/week,
and the dose of ribavirin was reduced by 200 mg/day as
soon as possible, and both were maintained at the lower
levels until the severity of the symptoms lessened to
Grade 1 or below. During the treatment, we did not use
erythropoietin or granulocyte-macrophage colony stimu-
lating factor in any patient.
Virological evaluation
Serum HCV-RNA levels were quantified and qualitatively
analyzed using a Cobas Amplicor HCV Monitor Test, ver-
sion 2.0 (detection range 6-5,000 kIU/ml, lower limit of
detection 50 IU/ml; Roche Diagnostics, Branchburg, NJ).
HCV genotype was determined by polymerase chain reac-
tion (PCR) amplification of the core region of the HCV
genome using genotype-specific PCR primers. [14]
Assessment of treatment efficacy
A rapid virological response (RVR) and an early virological
response (EVR) were defined as undetectable serum HCV-
RNA at week 4 and week 12 of the therapy, respectively.
An end-of-treatment response was defined as undetectable
HCV-RNA at the end of the therapy (i.e., week 48 for gen-
otype 1, week 24 for genotype 2). A sustained virological
response (SVR) was defined as undetectable HCV-RNA 24
weeks after completion of treatment. All assessment meth-
ods were defined according to published guidelines
[15,16]. Even if the treatment was prematurely discontin-
ued because of side effects or non-compliance, patients
could be considered to have an SVR on the basis of their
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serum HCV-RNA results at the 24-week follow-up. Non-
response was defined as a lack of HCV-RNA clearance
during treatment and at follow-up. During the follow-up
period, clinical, biochemical, and qualitative serum HCV-
RNA evaluations were performed every 3 months.
Statistical analysis
Variables were compared between groups by the chi-
squared test, Fisher’s exact probability test, and the Mann-
Whitney U test. Group means, presented as mean values
± standard deviations, were compared using the Student’s
t-test. The influence of various factors on the response to
Peg-IFN and ribavirin combination therapy was evaluated
by univariate analysis. All variables found to be significant
in the univariate analysis were subjected to multivariate
analysis using logistic regression. The data were analyzed
using SPSS version 9.0 for Microsoft Windows (SPSS, Inc.,
Chicago, IL). All statistical analyses were based on two-
sided hypothesis tests with a significance level of P < 0.05.
Results
Patients
The baseline characteristics of the elderly patients enrolled
in the present study are shown in Table 1. The number of
genotype 1 and 2 patients was 86 (79.6%) and 22 (20.4%),
respectively. No patients with HCV genotype 3 or 4 were
included in the present study because there are very few
patients with these genotypes in Japan. All the patients
had a high viral load (≥ 10 klU/ml), according to the Japa-
nese criteria. The number of patients aged ≥ 70 years was
24 (22.2%). The oldest patient was an 81-year-old male,
and he achieved an SVR.
Assessment of treatment response
SVR rates in the younger patients and the elderly
patients according to their HCV genotype were 41.5%
(100/241) and 40.7% (35/86) for genotype 1 and 89.7%
(70/78) and 86.4% (19/22) for genotype 2, respectively.
In terms of SVR rates, there were no significant differ-
ences between the two age groups according to HCV
genotype (P = 0.899 for genotype 1 and P = 0.703 for
genotype 2, respectively) (Table 2).
Among the elderly patients, the overall SVR rate was
50% (54/108). An RVR was obtained in 24 patients (10 of
genotype 1, 14 of genotype 2), an EVR was obtained in 61
patients (41 of genotype 1, 20 of genotype 2), and an end-
of-treatment response was obtained in 89 patients (68 of
genotype 1, 21 of genotype 2). The number of patients
with a non-response was 19 (18 of genotype 1, 1 of geno-
type 2). All the patients who demonstrated an RVR
achieved an SVR, and 47 (77%) of the 61 patients who
obtained an EVR achieved an SVR. Among the 47 patients
who did not obtain an EVR, only seven (14.9%) achieved
an SVR. According to gender, 33 males (61.1%) and 21
females (38.9%) achieved an SVR. Among the 63 patients
who completed at least 80% of the scheduled Peg-IFN
dose, 36 (57.1%) achieved an SVR; similarly, among the 63
patients who completed at least 80% of the scheduled riba-
virin dose, 36 (57.1%) achieved an SVR. Among the 47
patients who completed at least 80% of the scheduled Peg-
IFN-alpha2b dose, ribavirin dose, and scheduled treatment
duration (80/80/80 adherence, as mentioned elsewhere
[17]), 27 (57.4%) demonstrated an SVR.
Factors contributing to SVR in elderly patients
In our univariate analysis of factors contributing to an
SVR in elderly patients, gender (P = 0.021), HCV geno-
type (1 or 2) (P < 0.001), platelet count (P = 0.003), the
Table 1 Baseline characteristics of patients aged ≥ 65
years (n = 108)
Category
n or mean ± SD
Gender (Male/Female) 54/54
Age68.2 ± 2.8
Body Weight (kg)
Body mass index (kg/m2)
58.4 ± 9.5
23.3 ± 3.0
History of interferon therapy (yes/no)40/68
History of diabetes mellitus (yes/no)19/89
History of hypertension (yes/no)
White blood cells (/mm3)
Red blood cells (× 104/mm3)
47/61
4909 ± 1332
436.1 ± 39.8
Hemoglobin (g/dL)
Platelets (× 104/mm3)
13.8 ± 1.2
15.3 ± 3.9
AST (IU/L)65.2 ± 37.3
ALT (IU/L) 76.0 ± 65.5
AFP (ng/ml) 15.7 ± 31.4
Histology (METAVIR) Fibrosis (1/2/3/4)22/41/37/8
Histology (METAVIR) Activity (1/2/3)30/51/27
HCV genotype (1/2)86/22
Serum HCV RNA (KIU/ml) 1650 ± 1521
Peg-IFN dose (g/kg/week)1.22 ± 0.32
Total Peg-IFN dose > 80% (yes/no)63/45
Daily ribavirin dose (mg/kg) 9.58 ± 2.93
Total ribavirin dose > 80% (yes/no)63/45
Data are shown as absolute values or mean ± standard deviation. AST
aspartate aminotransferase; ALT alanine aminotransferase; AFP alpha-
fetoprotein; HCV hepatitis C virus; Peg-IFN pegylated interferon
Table 2 SVR rates between patients aged < 65 years and
patients aged ≥ 65 years according to HCV genotype
Age < 65 (n = 319)Age ≥ 65 (n = 108)
P valuea
SVR rate
(Genotype 1)
41.5% (100/241)40.7% (35/86)0.899
SVR rate
(Genotype 2)
89.7% (70/78)86.4% (19/22)0.703
HCV hepatitis C virus; SVR sustained virological response;aFisher’s exact test
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presence of an RVR (P < 0.001), and the presence of an
EVR (P < 0.001) contributed significantly (Table 3).
However, in our multivariate analysis of these five fac-
tors by logistic regression, the presence of an EVR was
the only significant factor (odds ratio: 0.115, 95% confi-
dence interval: 0.040-0.330, P < 0.001) (Table 4).
Tolerability and adverse events
There was no significant difference in the treatment dis-
continuation rate between younger patients and elderly
patients (10.3% (33/319) and 13.9% (15/108), respectively;
P = 0.378) (Table 5). The causes of treatment discontinua-
tion are shown in Table 5. In eight younger patients and
four elderly patients, the attending physician decided to
discontinue treatment because the viral load had not
decreased by week 24 of the treatment. There were no
adverse events that required hospitalization.
Discussion
In ageing chronic hepatitis C patients, especially those
over 60 years, liver fibrosis is accelerated and the inci-
dence of HCC is increased [18,19]. Among aged patients,
improving the liver fibrosis and decreasing the risk of
HCC are mainly achievable by eradication of the hepatitis
C virus [2]. Therefore, the primary goal of the IFN ther-
apy in elderly patients should be HCV eradication.
In the present study, there was no significant differ-
ence in SVR rate between the two age groups according
to HCV genotype. Moreover, there was no significant
difference in the treatment discontinuation rate between
the two age groups. Our data suggest that Peg-IFN-
alpha2b and ribavirin combination therapy is just as
Table 3 Univariate analysis of factors contributing to an SVR in elderly patients (n = 108)
Risk factor SVR (n = 54) non SVR (n = 54)
P value
Gender (male/female)33/2121/330.021
HCV genotype, (1/2)35/1951/3 < 0.001
Previous IFN therapy, (yes/no) 16/3824/30 0.163
Diabetes mellitus, (yes/no)7/47 12/42 0.312
Hypertension, (yes/no)
Body mass index (kg/m2), mean ± SD
White blood cells (/mm3), mean ± SD
22/3225/290.698
23.0 ± 3.023.7 ± 3.0 0.212
4948 ± 14124869 ± 12600.761
Hemoglobin (g/dL), mean ± SD
Platelets (× 104/mm3), mean ± SD
13.9 ± 1.213.8 ± 1.2 0.583
16.4 ± 4.2 14.2 ± 3.30.003
AST (IU/L), mean ± SD 69.1 ± 44.0 61.3 ± 29.20.280
ALT (IU/L), mean ± SD86.9 ± 80.765.1 ± 43.70.084
AFP (ng/ml), mean ± SD 12.1 ± 19.619.4 ± 39.7 0.228
Fibrosis score, (F1,2/F3,4)36/18 27/270.079
Serum HCV RNA (KIU/ml), mean ± SD1290 ± 1441 1343 ± 12650.838
Peg-IFN does (μg/kg week), mean ± SD1.23 ± 0.31 1.21 ± 0.300.494
Daily ribavirin dose (mg/kg), mean ± SD9.68 ± 2.969.48 ± 2.920.268
80/80/80 adherence, (yes/no)27/2720/34 0.244
rapid virological response, (yes/no)24/30 0/54 < 0.001
early virological response, (yes/no)47/714/40 < 0.001
Data are shown as absolute values or mean ± standard deviation. AST aspartate aminotransferase; ALT alanine aminotransferase; AFP alpha-fetoprotein; HCV
hepatitis C virus; Peg-IFN pegylated interferon; SVR sustained virological response
Table 4 Multivariate analysis of factors contributing to
an SVR in elderly patients
Risk factorOdds ratio95% confidence interval
P value
RVR
yes1 0.998
no0.0000.000
EVR
yes1
no 0.1150.040-0.330< 0.001
HCV genotype
10.534 0.093-3.0500.480
21
Gender
male 1.0550.370-3.0040.921
female1
Platelet count
> 15 × 104/mm3
≤ 15 × 104/mm3
1
0.838 0.285-2.4680.748
RVR rapid virological response; EVR early virological response; HCV hepatitis C
virus
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tolerable and effective in elderly patients as in younger
patients.
The SVR rate and the discontinuation rate of patients
aged ≥ 65 years in the present study are better than those
of previous studies [20-24]. Oze et al. reported that the
Peg-IFN dose affects the virologic response [25], and
Hiramatsu et al. reported that ribavirin dose reduction
increases the relapse rate [26]. However, in the present
study, there were no significant relationships between the
total Peg-IFN dose, total ribavirin dose, or treatment
duration and SVR. These differences may have arisen
because the previous studies were conducted mainly in
patients aged ≤ 65 years. In the case of elderly patients,
maintaining drug therapy at the standard dose often
causes side effects, which makes treatment discontinua-
tion or significant treatment dose reduction inevitable.
Oze et al. [24] investigated the efficacy and adverse
effects of Peg-IFN plus ribavirin therapy in aged patients
with chronic hepatitis C. We compared their SVR and
treatment discontinuation rates with ours according to
the dose of Peg-IFN and ribavirin. Although Oze et al.
[24] used a larger dose of both Peg-IFN and ribavirin
than we did (Peg-IFN dose: 1.22 ± 0.32 μg/kg/week (our
data) vs. 1.44 ± 0.18 μg/kg/week (Oze et al.); ribavirin
dose: 9.58 ± 2.93 mg/kg/day (our data) vs. 11.5 ± 1.7 mg/
kg/day (Oze et al.)), the SVR rate was 40.7% in genotype
1 elderly patients in our study and less than 30% in geno-
type 1 elderly patients in the study by Oze et al. The
treatment discontinuation rate in elderly patients was
also significantly different between the studies: 13.9% in
our study vs. less than 30% in the study by Oze et al. A
recent large-scale study demonstrated that the SVR rate
did not differ between standard-dose (1.5 μg/kg/week)
and low-dose (1.0 μg/kg/week) Peg-IFN-alpha2b therapy
[27]. In fact, in elderly patients, dose reduction in a rela-
tively early phase, based on careful monitoring of side
effects, may prevent treatment discontinuation and lead
to an improved SVR rate.
Sezaki et al. reported that in elderly patients, the
response to Peg-IFN and ribavirin combination therapy
is worse in female than in male patients [28]. Our data
are in agreement with this (SVR of 61.1% in males and
38.9% in females; P = 0.021).
In our multivariate analysis, the presence of an EVR was
the only factor contributing significantly to an SVR.
Although the positive predictive value for an RVR was
100% (24/24), it was not a significant factor in the multi-
variate analysis probably because an SVR was achieved
without an RVR in many cases. The key to successful IFN
therapy in elderly patients is likely to be achieving an EVR.
However, if this requires maintaining a high Peg-IFN dose,
there is a high possibility that subsequent large dose reduc-
tion or even treatment discontinuation will be needed.
Thus, careful monitoring is necessary in elderly patients,
especially within the first 12 weeks of their treatment.
Moreover, if an EVR is not achieved, early discontinuation
of treatment may be important in terms of preventing
unnecessary treatment and side effects, because, in the pre-
sent study, among the 47 patients who did not obtain an
EVR, only seven (14.9%) achieved an SVR.
This study has several limitations. First, our study is a
retrospective study. Second, the number of elderly
patients in the present study was low. In our multivariate
analysis, the presence of an EVR was the only significant
factor contributing to an SVR in elderly patients. How-
ever, in general, the four factors that were significant in
our univariate analysis (i.e., the presence of an RVR, gen-
der, HCV genotype, and platelet count) are also reported
to be significant predictive factors for an SVR [21-26].
Therefore, we should interpret our results with caution,
and larger studies are needed. Third, all patients who had
serious underlying diseases were excluded from our
study. In elderly patients with serious underlying dis-
eases, an ursodeoxycholic acid and/or glycyrrhizin-con-
taining preparation (Stronger Neo-Minophagen C) will
be needed when serum alanine aminotransferase levels
are higher than the normal upper limit, because these
patients would be expected to experience serious side
effects from Peg-IFN-alpha2b plus ribavirin combination
therapy or other IFN therapy.
Therefore, it is disputable whether the results of our
study are applicable to all elderly patients, who often
have underlying diseases. These issues should be clari-
fied in future prospective studies.
Conclusion
In conclusion, the effects of Peg-IFN-alpha2b plus riba-
virin combination therapy for HCV infection in elderly
patients are not always inferior to those in younger
patients. Peg-IFN-alpha2b plus ribavirin combination
therapy may be safely extended to elderly patients who
have no serious underlying disease.
Table 5 Causes of treatment discontinuation for the two age groups
Aged < 65 years group(n = 33)Aged ≥ 65 years group(n = 15)
Anemia95
Thrombopenia93
General fatigue73
Poor response to therapy84
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Acknowledgements
We would like to thank Haruko Takada for the data collection.
Author details
1Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital,
Osaka, Japan.2Department of Gastroenterology and Hepatology, Osaka Red
Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan.
Authors’ contributions
YO, TK, SS, AS, and TI participated in the design of the study and performed
the statistical analysis; RK helped to draft the manuscript. EI, SA, YK, TI, HT,
FM, JN, KH, and SH collected the data. All authors have read and approved
the final manuscript.
Competing interests
The authors declare that they have no competing interests. None of the
authors has had within the past 12 months any financial relationship with a
biotechnology manufacturer, a pharmaceutical company, or other
commercial entity that has any interest in the subject matter, materials, or
processes discussed in the manuscript.
Received: 6 September 2011 Accepted: 10 March 2012
Published: 10 March 2012
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doi:10.1186/1756-0500-5-135
Cite this article as: Nishikawa et al.: The effect of pegylated interferon-
alpha2b and ribavirin combination therapy for chronic hepatitis C
infection in elderly patients. BMC Research Notes 2012 5:135.
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