Pegylated interferon a-2a versus standard interferon
a-2a for treatment-naı¨ve dialysis patients with
chronic hepatitis C: a randomised study
C-H Liu,
1
C-C Liang,
2
J-W Lin,
3
S-I Chen,
3
H-B Tsai,
4
C-S Chang,
4
P-H Hung,
5
J-H Kao,
6
C-J Liu,
1,7
M-Y Lai,
1
J-H Chen,
8
P-J Chen,
1,6,7
J-H Kao,
1,6,7
D-S Chen
1

1
Department of Internal
Medicine, National Taiwan
University Hospital, Taipei,
Taiwan;
2
Department of Internal
Medicine, Far Eastern Memorial
Hospital, Taipei, Taiwan;
3
Department of Internal
Medicine, National Taiwan
University Hospital, Yun-Lin
Branch, Yun-Lin County, Taiwan;
4
Division of Nephrology,
Department of Medical Affairs,
St. Martin De Porres Hospital,
Chia-Yi, Taiwan;
5
Department of
Internal Medicine, Chiayi
Christian Hospital, Chia-Yi,
Taiwan;
6
Departments of
Medical Research, National
Taiwan University Hospital,
Taipei, Taiwan;
7

Hepatitis
Research Center, National
Taiwan University Hospital,
Taipei, Taiwan;
8
Department of
Pathology, National Taiwan
University Hospital, Yun-Lin
Branch, Yun-Lin County, Taiwan
Correspondence to:
Professor J-H Kao, Hepatitis
Research Center, National
Taiwan University Hospital, 7
Chung-Shan South Road, Taipei
100, Taiwan;
Revised 6 August 2007
Accepted 28 August 2007
Published Online First
19 September 2007
ABSTRACT
Background: Chronic hepatitis C virus (HCV) infection is
prevalent in dialysis patients, and standard interferon
monotherapy is the current standard of care for such
patients.
Aim: To investigate whether pegylated interferon has a
better therapeutic efficacy and safety profile than
standard interferon in dialysis patients with chronic
hepatitis C.
Methods: 50 such patients were randomly assigned to
receive either pegylated interferon a-2a 135 mg sub-

cutaneously once per week or standard interferon a-2a 3
million units subcutaneously thrice per week for
24 weeks. The primary efficacy and safety end points
were sustained virological response (SVR) by intention-to-
treat analysis and treatment-related withdrawal rate
during the study.
Results: In univariate analysis, patients receiving
pegylated interferon a-2a tended to have a higher
sustained virological response (SVR) than those receiving
standard interferon a-2a (48% vs 20%, p =0.07). By
using multivariate analysis, treatment with pegylated
interferon a-2a (p =0.02) and pretreatment HCV RNA
level ,800 000 IU/ml (p = 0.007) were independently
predictive of an SVR. All patients failing to achieve a rapid
virological response (RVR) could not achieve an SVR. In
addition, patients receiving pegylated interferon a-2a had
a significantly lower treatment-related withdrawal rate
than those receiving standard interferon a-2a (0% vs
20%, p = 0.04).
Conclusions: Pegylated interferon a-2a once weekly
provides more effective and safer therapy than standard
interferon a-2a thrice weekly for treatment-naı¨ve dialysis
patients with chronic hepatitis C.
Chronic hepatitis C virus (HCV) infection is
common in dialysis patients, with the reported
prevalence and annual incidence ranging from 3 to
80% and 2.9%, respectively.
1–4
Although dialysis
patients with HCV infection usually present with

mild symptoms and mild elevation of serum
alanine aminotransferase (ALT) levels, previous
studies have shown that these patients harbour
higher liver-related morbidity and mortality rates
at the dialysis stage,
5–8
and poor graft and patient
survival after renal transplantation.
9–11
Pegylated interferon and ribavirin have become
the mainstay therapy for chronic hepatitis C
patients with normal renal function, with an
overall sustained virological response (SVR) rate
of 54–61%.
12
However, ribavirin is currently
considered contraindicated in dialysis patients due
to the risk of severe haemolytic anaemia.
13–15
In
dialysis patients with chronic hepatitis C, two
meta-analyses indicated that the SVR rates were
33–37% with standard interferon a 1–6 million
units (MU) for 6–12 months. However, the corre-
sponding drop-out rates ranged from 17 to
29.6%.
16 17
Recently, small non-randomised studies
on the use of pegylated interferon a showed that
patients receiving pegylated interferon a-2a 135–

180 mg once per week had a more favourable SVR
rate (33–75%) than those receiving pegylated
interferon a-2b 0.5–1.0 mg/kg once per week
(12.5%).
18–21
With these lines of evidence, the recent Asian
Pacific Association for the Study of the Liver
(APASL) consensus statements on the diagnosis,
management and treatment of HCV infection
recommends that only standard interferon mono-
therapy is used for the treatment of dialysis
patients with chronic hepatitis C because there
was no report at the time of better efficacy and
safety of pegylated interferon.
22
We thus conducted
a randomised trial to evaluate the efficacy and
safety of pegylated interferon a-2a versus standard
interferon a-2a in treatment-naı¨ve dialysis patients
with chronic hepatitis C.
MATERIALS AND METHODS
Patients
Dialysis patients aged between 18 and 65 years
who were naı¨ve to interferon-based therapy and
fulfilled the following criteria were eligible for this
study: presence of anti-HCV antibody (Abbott
HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) and
HCV RNA for more than 6 months, receiving
regular dialysis therapy, and with creatinine
clearance of less than 10 ml/min/1.73 m

2
of body
surface area.
Patients were excluded from the study if they
had neutropenia (neutrophil count ,1500/mm
3
),
thrombocytopenia (platelet count ,90 000/ml
3
),
co-infection with hepatitis B virus (HBV) or HIV,
chronic alcohol abuse (daily alcohol consumption
.20 g/day), autoimmune liver diseases, decom-
pensated cirrhosis (Child–Pugh class B or C),
neoplastic diseases, organ transplantation or
immunosuppressive therapy, evidence of drug
abuse, poorly controlled autoimmune diseases,
cardiopulmonary diseases, neuropsychiatric disor-
ders and diabetes mellitus, or were unwilling to
take contraception during the study.
Hepatitis
Gut 2008;57:525–530. doi:10.1136/gut.2007.133884 525
Study design
This randomised, controlled clinical trial was conducted in four
centres (National Taiwan University Hospital, Far Eastern
Memorial Hospital, Chiayi Christian Hospital and St. Martin De
Porres Hospital) in Taiwan from July 2005 to January 2007. The
protocols were approved by the Ethical Committee of each
participating centre, and all patients provided written informed
consent before enrolment. The study was conducted in accordance

with the principles of the Declaration of Helsinki and the
International Conference on Harmonization for Good Clinical
Practice. Eligible patients were randomly assigned in a 1:1 ratio to
receive either once weekly, subcutaneous injection of 135 mg
pegylated interferon a-2a (Pegasys, F. Hoffmann-LaRoche, Basel,
Switzerland) or thrice weekly, subcutaneous injection of 3 MU
standard interferon a-2a (Roferon, F. Hoffmann-LaRoche, Basel,
Switzerland) for 24 weeks. Randomisation was performed by a
computer-generated random number table. Participants received
the study drugs on an outpatient basis for 24 weeks and then were
followed for 24 weeks after the cessation of therapy. Furthermore,
they received outpatient visits to assess the efficacy and safety at
weeks 1, 2, 4, 6 and 8 of the study and then monthly until the end
of follow-up.
Laboratory tests, including haemogram, coagulation profiles and
serum ALT levels, were assessed at each outpatient visit. Serum
HCV RNA levels were evaluated quantitatively at baseline and at
week 12 of the study (Cobas Amplicor HCV Monitor v2.0, Roche
Molecular Systems, Pleasanton, CA; with a detection cut-off level
of 600 IU/ml) and qualitatively at weeks 4, 24 and 48 of the study
(Cobas Amplicor HCV v2.0, Roche Molecular Systems,
Pleasanton, CA; with a detection cut-off level of 50 IU/ml).
HCV genotyping was performed at baseline by a reverse
hybridisation technique (Inno-LiPA HCV II, Innogenetics,
Ghent, Belgium). The rapid virological response (RVR) was
defined as undetectable HCV RNA by a sensitive qualitative test
at week 4 of the study. The early virological response (EVR) was
defined as at least a 2-log decrease of HCV RNA level by a
quantitative test from baseline to week 12 of the study, and the
end of treatment virological response (ETVR) was defined as

undetectable HCV RNA by a sensitive qualitative test at week 24
of the study. Liver biopsies at baseline and at the end of follow-up
were performed using 16-gauge Temno Evolution
TM
biopsy
needles (Allegiance, McGaw Park, IL) 30–60 min after the infusion
of 0.3 mg of deamino-8-
D-arginine vasopressin (DDAVP) per
kilogram of body weight.
23
All biopsy specimens were assessed
according to the modified histological activity index (HAI) score
24
by one experienced pathologist who was unaware of the clinical
status of study subjects. The HAI scores range from 0 to 24, with
inflammation scores graded from 0 (none) to 18 (severe) and
fibrosis scores graded from 0 (none) to 6 (cirrhosis).
Assessment of efficacy
The primary efficacy end point was SVR, defined as undetect-
able HCV RNA by a sensitive qualitative test at week 48 of the
study by intention-to-treat (ITT) analysis. The secondary
efficacy end point was histological response, defined as a
decrease of at least 2 points in the post-treatment to
pretreatment liver biopsies by the modified HAI score.
Assessment of safety
Participants received laboratory tests and evaluation of adverse
events on an outpatient basis to assess safety. They were
considered withdrawn from the study if they missed four
consecutive weeks of therapy or if the investigators were
concerned about the safety of the treatment. Patients who

withdrew from the study because of intolerance to adverse
events were encouraged to receive outpatient visits without
therapy until the end of the follow-up. Dosage reduction to
pegylated interferon a-2a 90 mg once weekly, standard inter-
feron a-2a 1.5 MU thrice weekly or cessation of treatment was
determined according to the severity of adverse events and the
laboratory abnormalities (dosage reduction, neutrophil count
,750/mm
3
or platelet count ,50 000/ml
3
; cessation of treat-
ment, neutrophil count ,500/mm
3
or platelet count ,30 000/
ml
3
). If the laboratory abnormalities and the severity of adverse
events improved or resolved after dosage reduction or treatment
cessation, a return to the initial dose was permitted. The
primary safety end point was the treatment-related withdrawal
rate, defined as premature cessation of therapy or loss to follow-
up off therapy due to treatment-related adverse events.
Statistical analysis
Statistical analyses were performed using the Statistical
Program for Social Sciences (SPSS 11.0 for windows; SPSS
Inc., Chicago, IL). The estimated sample size of 52 patients (26
in each group) was based on a type I error rate of a = 0.05, and a
type II error rate of b = 0.20 for a primary two-sided test, with
the assumption of a 35% difference in SVR rates (52% SVR in

the pegylated interferon a-2a group vs 17% SVR in the standard
interferon a-2a group). The independent Student t test was
used to compare quantitative variables, and x
2
test or Fisher’s
exact test was used for qualitative variables. ITT analyses for
efficacy and safety were performed on the basis of the patients
who received at least one dose of the study medication except
for changes from baseline in histological findings (secondary
efficacy end point). Per-protocol (PP) analysis for efficacy was
performed on the basis of the patients who completed the
follow-up study. The secondary efficacy end point was analysed
only in patients who had undergone pretreatment and post-
treatment liver biopsies. The relatedness of pretreatment and
on-treatment variables to SVR was examined by univariate
analysis, multivariate logistic regression analysis and x
2
test. A p
value ,0.05 was considered statistically significant. All statis-
tical tests were two-tailed.
RESULTS
Patient characteristics
Of the 66 patients screened, 16 did not meet the inclusion
criteria and were excluded from the study. The reasons for
exclusion were undetectable HCV RNA in seven, presence of
hepatocellular carcinoma in two, decompensated cirrhosis in
one, HCV and HBV co-infection in two, poorly controlled
diabetes mellitus in one, severe heart diseases in one and
reluctance to receive treatment in two (fig 1). The baseline
characteristics of the eligible patients with pegylated interferon

a-2a or standard interferon aa-2a were comparable (table 1).
Treatment was completed in 100% and 84%, and follow-up was
completed in 100% and 88%, in patients receiving pegylated
interferon a-2a and standard interferon a-2a, respectively. The
reasons for incomplete treatment were intolerable adverse
events in four, and for incomplete follow-up were intolerable
adverse events in two and death due to cardiogenic pulmonary
oedema 4 weeks off therapy in one.
Virological response
Table 2 shows the virological responses in dialysis patients who
received pegylated interferon a-2a or standard interferon a-2a by
Hepatitis
526 Gut 2008;57:525–530. doi:10.1136/gut.2007.133884
ITT and PP analyses. There were no significant differences
between pegylated interferon a-2a and standard interferon a-2a
groups for RVR rates (60% vs 44%, p = 0.40, ITT analysis; 60%
vs 45%, p = 0.39, PP analysis), EVR rates (92% vs 88%, p = 1.00,
ITT analysis; 92% vs 86%, p = 0.65, PP analysis) and SVR rates
(48% vs 20%, p = 0.07, ITT analysis; 48% vs 23%, p = 0.13, PP
analysis). In contrast, patients receiving pegylated interferon a-
2a had a significantly higher ETVR rate than those receiving
standard interferon a-2a (92% vs 60%, p = 0.02, ITT analysis;
92% vs 64%, p = 0.03, PP analysis).
Histological response
Pretreatment and post-treatment paired liver biopsies were
available in 41 patients (82%). Histological improvement
occurred after either pegylated interferon a-2a or standard
interferon a-2a therapy, but did not show statistical differences
in either inflammatory scores (p = 0.14), fibrosis scores
(p = 0.28), total scores (p = 0.13) or percentage of a decrease

of at least 2 points of total scores (p = 0.12). In contrast,
patients who achieved SVR had a statistically significant
improvement of inflammatory scores (p,0.001), fibrosis scores
(p = 0.004), total scores (p,0.001) and percentage of a decrease
Figure 1 Flow diagram of the trial.
Table 1 Baseline characteristics
Characteristics
Pegylated
interferon a-2a
(n = 25)
Standard interferon
a-2a (n = 25) p Value
Age (years) 48.2 (12.4) 49.4 (10.5) 0.72
Male gender, n (%) 16 (64) 14 (56) 0.56
Body mass index 22.4 (1.3) 22.9 (1.6) 0.47
Haemoglobin (g/l) 11.5 (1.5) 11.7 (1.8) 0.68
White blood cell count
(610
9
/l)
6.1 (1.7) 6.3 (1.8) 0.83
Platelet count (6 10
9
/l) 183 (68) 174 (40) 0.57
ALT (/ULN) 1.4 (0.7) 1.5 (0.8) 0.72
Creatinine (mg/dl) 10.8 (3.3) 10.2 (2.7) 0.50
Viral load, log
10
(IU/ml) 6.3 (0.5) 6.1 (0.6) 0.22
Genotype, n (%) 0.79

1a 2 (8) 2 (8)
1b 18 (72) 17 (68)
2a 5 (20) 5 (20)
2b 0 (0) 1 (4)
Total modified HAI score 10.9 (3.9) 8.8 (3.3) 0.07
Fibrosis score, n (%)
Significant fibrosis (>3) 15 (60) 12 (48) 0.31
Cirrhosis (6) 1 (4) 1 (4) 0.70
Values are given as the mean (SD) unless specified otherwise.
ALT, alanine aminotransferase; HAI, histological activity index; ULN, upper limit of
normal.
Table 2 Virological responses to pegylated interferon a-2a and
standard interferon a-2a by intention-to-treat and per-protocol analyses
Pegylated
interferon a-2a Standard interferon a-2a
p Value
Intention-to-treat
analysis* (n = 25) (%) (n = 25) (%)
RVR 15 (60) 11 (44) 0.40
EVR 23 (92) 22 (88) 1.00
ETVR 23 (92) 15 (60) 0.02
SVR 12 (48) 5 (20) 0.07
Per-protocol analysis{ (n = 25) (%) (n = 22) (%)
RVR 15 (60) 10 (45) 0.39
EVR 23 (92) 19 (86) 0.65
ETVR 23 (92) 14 (64) 0.03
SVR 12 (48) 5 (23) 0.13
*Patients who received at least one dose of the study medication.
{Patients who completed follow-up of interferon-based therapy.
ETVR, end of treatment virological response; EVR, early virological response; RVR,

rapid virological response; SVR, sustained virological response.
Hepatitis
Gut 2008;57:525–530. doi:10.1136/gut.2007.133884 527
of at least 2 points of total scores (p,0.001) compared with
those who did not achieve SVR (table 3).
Safety
Fever was more frequently observed in patients receiving
standard interferon a-2a than in those receiving pegylated
interferon a-2a (44% vs 12%, p = 0.03) (table 4). Other
constitutional symptoms were comparable in both groups.
None of them needed dose reduction or cessation of treatment
due to neutropenia. More patients receiving standard interferon
a-2a needed dose modification than those receiving pegylated
interferon a-2a due to thrombocytopenia, but the difference
was not statistically significant (20% vs 12%, p = 0.70). Four
patients stopped standard interferon a-2a at weeks 12, 16, 16
and 20 of treatment, respectively, due to treatment-related
adverse events (retinal haemorrhage, fever, fatigue and derma-
titis), but two of them completed follow-up. Two patients
receiving standard interferon a-2a had treatment-related serious
adverse events: one had retinal haemorrhage with impaired
visual acuity at week 12 of treatment and one died from
cardiogenic pulmonary oedema 4 weeks off therapy. None of
the patients receiving pegylated interferon a-2a stopped treat-
ment prematurely or had serious adverse events during
treatment and follow-up. The treatment-related withdrawal
rate of patients receiving pegylated interferon a-2a was
significantly lower than that of patients receiving standard
interferon a-2a (0% vs 20%, p = 0.04).
Predictors of a sustained virological response

Table 5 shows the pretreatment and on-treatment predictors for
SVR. Baseline HCV RNA level with a cut-off level of
800 000 IU/ml and age with a cut-off level of 40 years were
significantly associated with SVR (p = 0.0001 and 0.01, respec-
tively), and treatment with pegylated interferon a-2a or
standard interferon a-2a was marginally significantly associated
with SVR (p = 0.07). Factors in the univariate analysis with a p
value ,0.10 entered into multivariate logistic regression analysis
to search for independent factors predictive of SVR. Both
baseline HCV RNA level >800 000 IU/ml (odds ratio (OR) 0.04,
95% CI 0.01 to 0.41, p = 0.007) and treatment with pegylated
interferon a-2a (OR 6.52, 95% CI 1.31 to 32.47, p = 0.02) were
independently associated with SVR. By week 4, 52% of patients
treated with either pegylated interferon a-2a or standard
interferon a-2a had RVR. While 65% of the patients with
RVR achieved SVR, none of the patients without RVR achieved
SVR (p,0.001).
DISCUSSION
With the high incidence and prevalence,
1–4
higher liver-related
co-morbidity at the dialysis stage,
5–8
poor graft and patient
survival,
9–11
and poor response to interferon-based therapy at the
post-transplantation stage,
25–28
dialysis patients with chronic

hepatitis C are encouraged to receive antiviral therapy at the
dialysis stage rather than at the post-transplantation stage.
Although small-scale clinical trials showed that standard
interferon or pegylated interferon in combination with ribavirin
may achieve a high SVR in dialysis patients, severe adverse
events frequently occurred
29–33
and routine use of ribavirin is not
recommended.
13–15 22 34
Two meta-analyses indicated that the
overall SVR rates of standard interferon monotherapy were 33–
37% in dialysis patients; however, varied dosage, duration and
response rates were observed.
16 17
Similarly, wide variation of
treatment responses (12.5–75%) and adverse events were also
observed with pegylated interferon a-2a or a-2b monother-
apy.
18–21
We thus conducted a randomised trial to compare the
efficacy and safety of pegylated versus standard interferon a-2a
directly in this special clinical setting. Although univariate
analysis failed to show the superiority of pegylated interferon a-
2a over standard interferon a-2a in achieving SVR, multivariate
analysis clearly demonstrated the better treatment response of
pegylated interferon a-2a. This discrepancy may be explained by
Table 3 Histological responses of pegylated interferon a-2a and
standard interferon a-2a, with or without a sustained virological
response

Pegylated
interferon a-2a
(n = 20)
Standard
Interferon a-2a
(n = 21) p Value
Change in inflammation
score
23.2 (3.4) 21.7 (2.6) 0.14
Change in fibrosis score 20.6 (0.7) 20.3 (0.6) 0.28
Change in total score 23.7 (3.8) 22.0 (2.9) 0.13
Percentage decrease of
total score >2
70 43 0.12
With SVR (n = 15)
Without SVR
(n = 26) p Value
Change in inflammation
score
24.9 (2.5) 21.0 (2.4) ,0.001
Change in fibrosis score 20.8 (0.6) 20.2 (0.6) 0.004
Change in total score 25.7 (2.5) 21.2 (2.7) ,0.001
Percentage decrease of
total sore >2
93 31 ,0.001
Values are given as the mean (SD).
Table 4 Incidence of adverse events during the study (number (%))
Adverse event
Pegylated interferon a-2a
(n = 25)

Standard interferon a-2a
(n = 25)
Fever* 3 (12) 11 (44)
Rigour 4 (16) 8 (32)
Fatigue 12 (48) 14 (56)
Headache 8 (32) 9 (36)
Myalgia 7 (28) 7 (28)
Insomnia 6 (24) 7 (28)
Irritability 3 (12) 5 (20)
Depression 2 (12) 3 (12)
Dizziness 2 (8) 2 (8)
Anorexia 5 (20) 11 (44)
Vomiting 3 (12) 5 (20)
Diarrhoea 2 (8) 5 (20)
Constipation 2 (8) 3 (12)
Cough 2 (8) 3 (12)
Dermatitis 5 (20) 6 (24)
Injection reaction 3 (12) 4 (16)
Hair loss/alopecia 5 (20) 7 (28)
Leucopenia 0 (0) 0 (0)
Thrombocytopenia 3 (12) 5 (20)
Serious adverse events
Retinal haemorrhage{ 0 (0) 1 (4)
Death{ 0 (0) 1 (4)
Overall withdrawal rate 0 (0) 5 (20)
Interferon related1 0 (0) 5 (20)
Non-interferon related 0 (0) 0 (0)
*p = 0.03.
{At week 12 after the treatment with impaired visual acuity.
{Cardiogenic pulmonary oedema 4 weeks off therapy with standard interferon a-2a

therapy (week 28) related to standard interferon therapy.
1Included four patients without completion of 24 weeks of standard interferon a-2a
therapy due to retinal haemorrhage, fever, fatigue and dermatitis, and one death
4 weeks off therapy with standard interferon a-2a therapy, p = 0.04.
Hepatitis
528 Gut 2008;57:525–530. doi:10.1136/gut.2007.133884
the relatively small cohort of patients, which precluded an even
distribution of all potential confounding factors affecting SVR.
It is known that the baseline HCV RNA level serves as an
important predictor of SVR.
35 36
After adjusting baseline viral
load, patients receiving pegylated interferon a-2a had a
significantly higher SVR rate than those receiving standard
interferon a-2a. Furthermore, the treatment-related withdrawal
rate in the standard interferon a-2a group was higher than that
in the pegylated interferon a-2a group. Taking these results
together, for the first time we demonstrated that 24-week
pegylated interferon a-2a was better than standard interferon a-
2a for treatment-naı¨ve dialysis patients with chronic hepatitis C
in terms of efficacy and safety.
Our study showed that patients who received standard
interferon a-2a were inferior to patients who received pegylated
interferon a-2a in achieving ETVR by either ITT or PP analyses.
None of the four patients in the standard interferon a-2a group
who stopped treatment prematurely at week 12–20 of treat-
ment due to adverse events had ETVR, although all of them had
EVR. In sharp contrast, all patients in the pegylated interferon
a-2a group could tolerate the treatment well without premature
discontinuation, and, therefore, all of them who had EVR had

ETVR. Because of the greater peak-to-trough drug concentra-
tion in patients with standard interferon than those with
pegylated interferon,
37
dialysis patients with standard interferon
may experience more severe adverse events that preclude
complete treatment. Therefore, virological relapse occurs early
after stopping the treatment. This fact also highlights that
dialysis patients with chronic hepatitis C should receive
pegylated interferon-based therapy.
Contrary to the concept that HCV genotype 1 and significant
hepatic fibrosis are associated with a poor SVR rate to interferon
monotherapy in HCV patients with normal renal function,
35 36
our results failed to show the significance of these factors in
predicting SVR. Instead, baseline HCV RNA level was the only
independent predictor for SVR. This may be explained by the
limited patient numbers in our study, or the inferior augmenta-
tion of host immunity with interferon therapy in dialysis
patients, which resulted in similar viral suppression across
different genotypes and fibrosis stages.
38–40
Further larger studies
are needed to examine the role of HCV genotype and hepatic
fibrosis for SVR in these patients.
Early prediction of virological response to interferon mono-
therapy during treatment can help docors to identify patients
who are unlikely to achieve SVR, and allow discontinuation of
treatment to relieve patient discomfort and to save additional
medical cost. In this study, none of the patients without RVR

could achieve SVR at the end of follow-up. Furthermore,
treatment failure was also observed in all dialysis patients
receiving 1.5–3 MU standard interferon for 12 months who had
detectable serum HCV RNA at month 2 of treatment.
41
To
decide whether to receive an extended duration of treatment
beyond 24 weeks in patients based on RVR and month 2 serum
HCV RNA level should be individualised and needs further
confirmation.
Although our data showed that dialysis patients with chronic
hepatitis C who received 24 weeks of pegylated interferon
monotherapy had a virological response comparable with that
of chronic hepatitis C patients with normal renal function who
received 48 weeks of pegylated interferon monotherapy,
35
the
overall SVR rate was far from satisfactory. Further large studies
focusing on the treatment duration and the addition of ribavirin
to achieve a higher SVR rate without compromising patient
tolerance and safety are awaited to optimise treatment in this
special clinical setting.
In conclusion, pegylated interferon a-2a is superior to
standard interferon a-2a in treatment-naı¨ve dialysis patients
with chronic hepatitis C. High pre-treatment HCV RNA level
and failure to achieve RVR are predictors of poor response to
interferon monotherapy.
Funding: The study was supported by grants from the National Taiwan University
Hospital, the National Science Council and Department of Health, Executive Yuan,
Taiwan.

Competing interests: None.
REFERENCES
1. Fabrizi F, Poordad FF, Martin P. Hepatitis C infection and the patient with end-stage
renal disease. Hepatology 2002;36:3–10.
2. Kao JH, Huang CH, Chen W, et al. GB virus infection in hemodialysis patients:
molecular evidence for nosocomial infection. J Infect Dis 1999;180:191–4.
Table 5 Pretreatment and on-treatment predictors of a sustained virological response
Pretreatment variables
Univariate
analysis Multivariate analysis{
p Value OR (95% CI) p Value
Treatment (pegylated interferon a-2a vs
standard interferon a-2a)
0.07 6.52 (1.31 to 32.47) 0.02
Age (>40 years old vs. ,40 years old) 0.01 0.20 (0.04 to 1.15) 0.07
Gender (male vs female) 0.37 – –
Body mass index 0.77 – –
ALT quotient (>1vs,1)* 1.00 – –
HCV RNA (>800 000 IU/ml vs
,800 000 IU/ml)
0.001 0.04 (0.01 to 0.41) 0.007
HCV genotype (type 1 vs type 2) 0.29 – –
Hepatic fibrosis (>3vs,3){ 0.56 – –
On-treatment variables Patients (n, %) With SVR (n, %) Without SVR (n, %) p Value1
With RVR 26 (52) 17 (65) 9 (35) ,0.001
Without RVR 24 (48) 0 (0) 24 (100)
*The alanine aminotransferase levels divided by the upper limit of normal (ULN).
{Modified histological activity index (HAI) fibrosis score.
{Factors with a p value ,0.10 by univariate analysis entering multivariate logistic regression analysis.
1SVR rates in patients with RVR vs patients without RVR.

ALT, alanine aminotransferase; HCV, hepatitis C virus; RVR, rapid virological response; SVR, sustained virological response.
Hepatitis
Gut 2008;57:525–530. doi:10.1136/gut.2007.133884 529
3. Hou CH, Chen WY, Kao JH, et al. Intrafamilial transmission of hepatitis C virus in
hemodialysis patients. J Med Virol 1995;45:381–5.
4. Furusyo N, Hayashi J, Kakuda K, et al. Acute hepatitis C among Japanese
hemodialysis patients: a prospective 9-year study. Am J Gastroenterol
2001;96:1592–600.
5. Maisonneuve P, Agodoa L, Gellert R, et al. Cancer in patients on dialysis for end-
stage renal disease: an international collaborative study. Lancet 1999;354:93–9.
6. Nakayama E, Akiba T, Marumo F, et al. Prognosis of anti-hepatitis C virus antibody-
positive patients on regular hemodialysis therapy. J Am Soc Nephrol 2000;11:1896–
902.
7. Stehman-Breen CO, Emerson S, Gretch D, et al. Risk of death among chronic
dialysis patients infected with hepatitis C virus. Am J Kidney Dis 1998;32:629–34.
8. Fabrizi F, Martin P, Dixit V, et al. Meta-analysis: effect of hepatitis C virus infection
on mortality in dialysis. Aliment Pharmacol Ther 2004;20:1271–17.
9. Mathurin P, Mouquet C, Poynard T, et al. Impact of hepatitis B and C virus on kidney
transplantation outcome. Hepatology 1999;29:257–63.
10. Hanafusa T, Ichikawa Y, Kishikawa H, et al. Retrospective study on the impact of
hepatitis C virus infection on kidney transplant patients over 20 years. Transplantation
1998;66:471–6.
11. Legendre C, Garrigue V, Le Bihan C, et al. Harmful long-term impact of hepatitis C
virus infection in kidney transplant recipients. Transplantation 1998;65:667–70.
12. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C.
N Engl J Med 2006;355:2444–51.
13. Strader DB, Wright T, Thomas DL, et al. American Association for the Study of Liver
Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology
2004;39:1147–71.
14. Dienstag JL, McHutchison JG. American Gastroenterological Association medical

position statement on the management of hepatitis C. Gastroenterology
2006;130:225–30.
15. Yee HS, Currie SL, Darling JM, et al. Department of Veterans Affairs Hepatitis C
Resource Center; management and treatment of hepatitis C viral infection:
recommendations from the Department of Veterans Affairs Hepatitis C Resource
Center program and the National Hepatitis C Program office. Am J Gastroenterol
2006;101:2360–78.
16. Russo MW, Goldsweig CD, Jacobson IM, et al. Interferon monotherapy for dialysis
patients with chronic hepatitis C: an analysis of the literature on efficacy and safety.
Am J Gastroenterol 2003;98:1610–5.
17. Fabrizi F, Dulai G, Dixit V, et al. Meta-analysis: interferon for the treatment of chronic
hepatitis C in dialysis patients. Aliment Pharmacol Ther 2003;18:1071–81.
18. Kokoglu OF, Ucmak H, Hosoglu S, et al. Efficacy and tolerability of pegylated-
interferon alpha-2a in hemodialysis patients with chronic hepatitis C. J Gastroenterol
Hepatol 2006;21:575–80.
19. Sporea I, Popescu A, Sirli R, et al. Pegylated-interferon alpha 2a treatment for
chronic hepatitis C in patients on chronic haemodialysis. World J Gastroenterol
2006;12:4191–4.
20. Chan TM, Ho SK, Tang CS, et al. Pilot study of pegylated interferon-alpha 2a in
dialysis patients with chronic hepatitis C virus infection. Nephrology 2007;12:11–7.
21. Russo MW, Ghalib R, Sigal S, et al. Randomized trial of pegylated interferon alpha-
2b monotherapy in haemodialysis patients with chronic hepatitis C. Nephrol Dial
Transplant 2006;21:437–43.
22. Asian Pacific Association for the Study of the Liver (APASL) Hepatitis C
Working Party. Asian Pacific Association for the Study of the Liver consensus
statements on the diagnosis, management and treatment of hepatitis C virus
infection. J Gastroenterol Hepatol 2007;22:615–33.
23. Mannucci PM, Remuzzi G, Pusineri F, et al. Deamino-8-
D-arginine vasopressin
shortens the bleeding time in uremia. N Engl J Med 1983;308:8–12.

24. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic
hepatitis. J Hepatol 1995;22:696–9.
25. Magnone M, Holley JL, Shapiro R, et al. Interferon-alpha-induced acute renal
allograft rejection. Transplantation 1995;59:1068–70.
26. Morales JM. Hepatitis C virus infection and renal disease after renal transplantation.
Transplant Proc 2004;36:760–2.
27. Rostaing L, Izopet J, Baron E, et al. Treatment of chronic hepatitis C with
recombinant alpha 2b interferon in kidney transplant recipients: preliminary results
and side effects. Transplant Proc 1995;27:948–50.
28. Huraib S, Iqbal A, Tanimu D, et al. Sustained virological and histological response
with pretransplant interferon therapy in renal transplant patients with chronic viral
hepatitis C. Am J Nephrol 2001;21:435–40.
29. Mousa DH, Abdalla AH, Al-Shoail G, et al. Alpha-interferon with ribavirin in the
treatment of hemodialysis patients with hepatitis C. Transplant Proc 2004;36:1831–
4.
30. Bruchfeld A, Stahle L, Andersson J, et al. Ribavirin treatment in dialysis patients
with chronic hepatitis C virus infection—a pilot study. J Viral Hepat 2001;8:287–92.
31. Tan AC, Brouwer JT, Glue P, et al. Safety of interferon and ribavirin therapy in
haemodialysis patients with chronic hepatitis C: results of a pilot study. Nephrol Dial
Transplant 2001;16:193–5.
32. Bruchfeld A, Lindahl K, Reichard O, et al. Pegylated interferon and ribavirin
treatment for hepatitis C in haemodialysis patients. J Viral Hepat 2006;13:316–21.
33. Rendina M, Schena A, Castellaneta NM, et al. The treatment of chronic hepatitis C
with peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed patients awaiting
renal transplant. J Hepatol 2007;46:768–74.
34. Liu CH, Liu CJ, Kao JH. Interferon-based therapy for dialysis patients with chronic
hepatitis C: progress and challenges. Nephrology 2007;12:8–10.
35. Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with
chronic hepatitis C. N Engl J Med 2000;343:1666–72.
36. Heathcote EJ, Shiffman ML, Cooksley WG, et al. Peginterferon alfa-2a in patients

with chronic hepatitis C and cirrhosis. N Engl J Med 2000;343:1673–80.
37. Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying
pharmacokinetics. Clin Pharmacokinet 2001;40:539–51.
38. Yoon JW, Gollapudi S, Pahl MV, et al. Naive and central memory T-cell lymphopenia
in end-stage renal disease. Kidney Int 2006;70:371–6.
39. Meier P, Dayer E, Ronco P, et al. Dysregulation of IL-2/IL-2R system alters
proliferation of early activated CD4+ T cell subset in patients with end-stage renal
failure. Clin Nephrol 2005;63:8–21.
40. Rico MA, Ruiz S, Subira D, et al. Virus-specific effector CD4+ T-cell responses in
hemodialysis patients with hepatitis C virus infection. J Med Virol 2004;72:66–74.
41. Degos F, Pol S, Chaix ML, et al. The tolerance and efficacy of interferon-alpha in
haemodialysis patients with HCV infection: a multicentre, prospective study. Nephrol
Dial Transplant 2001;16:1017–23.
Hepatitis
530 Gut 2008;57:525–530. doi:10.1136/gut.2007.133884