Nephrol Dial Transplant (2012) 27: 640–646
doi: 10.1093/ndt/gfr236
Advance Access publication 10 May 2011
Effect of interferon-alpha-based antiviral therapy on hepatitis C virusassociated glomerulonephritis: a meta-analysis
Bo Feng1, Garabed Eknoyan2, Zhong-sheng Guo1, Michel Jadoul3, Hui-ying Rao1, Wei Zhang1 and
Lai Wei1
1
Hepatology Institute, Peking University People’s Hospital, Beijing, China, 2Renal Section, Department of Medicine, Baylor College of
Medicine, Houston, TX, USA and 3Department of Nephrology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain,
Brussels, Belgium
Correspondence and offprint requests to: Lai Wei; E-mail: [email protected]
Abstract
Background. Hepatitis C virus (HCV) is associated with
various glomerulopathies, in which HCV is responsible
not only for the onset of glomerulopathy but also for its
progressive loss of kidney function. The effect of antiviral
treatment on the glomerular lesions and subsequent course
of kidney disease remains controversial. Therefore, we
performed a systematic analysis of the available evidence
on the effect of interferon (IFN)-a-based therapy on HCVassociated chronic kidney disease.
Methods. A meta-analysis was performed of controlled and
uncontrolled clinical studies related to IFNa-based antiviral
therapy and its impact on kidney function in HCV-associated
glomerulonephritis. Improvement of proteinuria and serum
creatinine levels after antiviral therapy was taken as the end
points of interest. Data from eligible studies selected according to protocols were analysed using Review Manager 5.0.
Results. Eleven clinical trials involving 225 patients were
included in our meta-analysis. At the end of antiviral therapy,
the summary estimate of the mean decrease in proteinuria
was 2.71 g/24 h [95% confidence interval (CI) 1.38–4.04,
P < 0.0001], P-value for heterogeneity 0.05 (I2 ¼ 53%). The
pooled decrease in mean serum creatinine levels was
0.23 mg/dL (95% CI 0.02–0.44, P ¼ 0.03), P-value for
heterogeneity 0.30 (I2 ¼ 17%). Comparison of nonsustained virological response (SVR) to SVR groups demonstrated a mean difference of proteinuria decrease in the
SVR group of 1.04 g/24 h (95% CI 0.20–1.89, P ¼ 0.02),
P-value for heterogeneity 0.21 (I2 ¼ 36%) and of serum
creatinine decrease of 0.05 mg/dL (95% CI 0.33 to 0.43,
P ¼ 0.80), P-value for heterogeneity 0.70 (I2 ¼ 0%).
Conclusions. Antiviral therapy based on IFNa can significantly decrease proteinuria and stabilize serum creatitine,
and therefore, should be undertaken in patients with HCVassociated glomerulonephritis. The improvement in protein
excretion is greater in those who achieve HCV RNA clearance, a finding in line with a causal role for HCV in
glomerulonephritis.
Keywords: chronic kidney disease; hepatitis C; interferon; meta-analysis
Introduction
Hepatitis C virus (HCV) is a leading cause of chronic liver
disease in the world. The World Health Organization
estimates that there are 170 million individuals with HCV
infection and an incidence of 3–4 million new cases per
year [1]. HCV infection is often associated with a number
of extrahepatic disorders, including cryglobulinemia,
glomerulonephritis, porphyria cutanea tarda, lichen planus,
seronegative arthritis, type 2 diabetes mellitus and
lymphoproliferative disorders [2]. An increasing number
of reports show that chronic HCV infection is associated
with various glomerulopathies such as membranoproliferative glomerulonephritis (MPGN), membranous glomerulonephritis, mesangioproliferative glomerulonephritis and
focal and segmental glomerulosclerosis [3–5], among
which MPGN, with or without cryglobulinemia, is the most
common type of glomerulopathy [6].
The renal lesions associated with HCV are attributed to
injury due to cryoglobulins and deposition of circulating
immune complexes containing HCV and its antibodies [7,
8]. HCV RNA has been detected in the serum of most and
in the renal parenchyma of some of these patients [9]. The
clinical manifestations of the glomerulopathy range from
isolated proteinuria to overt nephritic (20–30%) or nephrotic syndrome (20%), with variable degrees of progressive
loss of kidney function [3, 10]. Positive anti-HCV serologic
status has further been associated with an increased occurrence of infections [11], diabetes mellitus [12] and de novo
or recurrent glomerulopathy in kidney transplant recipients
[13]. As such, the treatment of patients with chronic kidney
diseases (CKD) who are infected with HCV should be
undertaken before they progress to end-stage renal disease
(ESRD) or require kidney transplantation [14].
The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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Treatment of HCV-associated glomerulopathy
HCV-related liver disease can be treated successfully
with antiviral therapy, along with eradication of HCV
infection [15]. However, the role of antiviral treatment in
HCV-associated glomerulonephritis has been controversial. The kidney plays a role in the catabolism and clearance
of both interferon (IFN)-a and ribavirin, and thus their
clearance is altered in patients with reduced kidney function [15], and these patients are subject to an increased
incidence and severity of side effects of both drugs. Additionally, the virological response and patient dropout rates
with antiviral therapy are ~40% and 20–30%, respectively
[16]. As a result, although several studies of antiviral treatment of hepatitis C in CKD patients have been reported, the
majority of them are uncontrolled studies and generally
include a small number of studied subjects. Non-responses
or relapses after IFNa discontinuation are frequent [6],
although some anecdotal studies report complete remission
in cases treated with IFNa alone or combined with ribavirin
[12,17–19]. Some reports suggest that IFNa therapy was
not useful or even harmful during the acute phase of kidney
disease [20, 21], while others report a good response during
the stationary phase of the disease [22, 23].
The primary goal of our study was to synthesize the
available evidence by a systematic analysis of the effect
of antiviral therapy on HCV-associated CKD based on a
meta-analysis of controlled and uncontrolled studies.
Subjects and methods
Criteria for inclusion
Studies included in this meta-analysis had to fulfil a set of criteria. They
had to be published in a peer-reviewed journal as a full paper. Controlled
or uncontrolled studies on CKD patients receiving antiviral therapy based
on IFNa were included. HCV infection was defined by positive testing for
anti-HCV antibody and HCV RNA in serum. Studies which included
ESRD patients on maintenance dialysis (hemo-or peritoneal dialysis),
and kidney transplant recipients were excluded. Studies were excluded
if they reported inadequate data on response to antiviral therapy or were
only published as abstracts or interim reports. Studies enrolling individuals
with positive serology for HBsAg or antibodies to HIV were excluded.
The decision to include or exclude a study was made independently of its
outcome.
641
The mean difference of outcomes to antiviral therapy was generated using
the random effects model. Heterogeneity was quantified using a chi-square
test, and the quantity of heterogeneity was evaluated using I2 statistic [24].
Sources of heterogeneity were assessed with subgroup analysis, which
were performed only when data from at least two studies were available
for each subgroup. Publication bias was measured by the test of funnel plot
asymmetry. The 5% significance level was used for alpha risk. Every
estimate was given with its 95% CI.
Studies reporting complete data on the levels of proteinuria and serum
creatinine were meta-analysed. Additionally, to investigate the effect of
sustained virological response (SVR) on outcomes of CKD patients with
HCV infection, the studies on case series, in which all cases were HCVassociated CKD patients receiving antiviral therapy and had similar clinical features, were grouped and analysed simultaneously as a whole
(named hereafter mixpaper) for increasing the patient number of SVR
and non-SVR groups. Here, SVR was defined as HCV RNA negative
24 weeks after cessation of treatment and non-SVR as failure to clear
HCV RNA from serum at the end of standard treatment or relapsers during
follow-up.
Results
Literature review
Our electronic and manual searches identified a total of
2089 citations (Figure 1). After review of titles, 1233 of
these were excluded for being irrelevant to anti-HCV
treatment in CKD patients. After screening by title and
abstract, 797 additional citations were excluded according
to protocol of eligible and ineligible studies. The remaining 59 studies were selected for full article review. By
carefully examining the full texts, eleven clinical trials
[7, 9, 10, 12, 19, 23,25–29] were included in our metaanalysis (Figure 1). There was full concordance between
the two independent reviewers with respect to the final
inclusion and exclusion of studies reviewed.
End points of interest
The primary outcome of interest was the level of proteinuria at the end of
therapy or during follow-up. The secondary outcome was the improvement in serum creatinine level at the end of therapy and follow-up.
Data sources and search strategy
Electronic searches of MEDLINE database and Embase, and manual
searches of selected specialty journals were performed to identify the
pertinent literature. The keywords ‘Hepatitis C Virus’, ‘Interferon’,
‘Chronic kidney Disease’ and their synonyms or related terms were used.
Reference lists from qualitative topic reviews and published clinical trials
were also searched. The search was limited to human studies that were
published in the English literature from January 1990 to April 2010. Data
extraction was conducted independently by two investigators (F.B. and
G.Z.S.). Inconsistent data were discussed with the other authors when
necessary. Consensus was achieved for all data inclusion before metaanalysis. Duplicate reports for the same study subjects were eliminated
and additional data were obtained through direct contact with investigators
when necessary.
Data synthesis and analysis
The analyses were performed using Review Manager 5.0. Continuous data
were expressed as the mean difference with 95% confidence interval (CI).
Fig. 1. Study screening flow chart.
642
Patient characteristics
Salient demographic characteristics of subjects enrolled in
the included studies are shown in Tables 1–3. Six studies
were from Europe, two from the USA, two from Asia and
one from Africa. Six of the selected studies were controlled
clinical trials and five uncontrolled prospective studies
(Table 1). Information on a total of 225 patients was provided
in the 11 studies (Table 2). Twelve of the 225 subjects were
lost to follow-up or terminated anti-viral therapy due to side
effects. The mean age of subjects ranged from 36 9 to
64 12 years old. The proportion of males ranged from 15.1
to 68.0%. HCV genotype was provided in seven studies
(Table 2). Five studies were based on IFNa monotherapy
and six on a combined IFNa and ribavirin regimen (Table 3).
Eight trials used conventional IFNa, while the other three
used both conventional IFNa and pegylated-IFNa (pegIFNa). The duration of anti-viral treatment ranged from
24 to 96 weeks. Among the 143 subjects who were treated
with anti-HCV therapy, 51 achieved SVR. Data at baseline
on proteinuria and creatinine serum levels are shown in
Table 2. Some of the studies provided serum alanine aminotransferase levels, histological patterns of HCV-related
glomerulonephritis and other risk factors such as hypertension, but there were insufficient data about their influence
on CKD and IFN response.
Summary estimates of outcomes between pre- and posttreatment
Based on completeness of data reported, seven studies were
analysed for proteinuria and six for serum creatinine
evolution between baseline and after treatment using
Review Manager 5.0 software (data of serum creatinine
not reported in reference [19]). Figure 2 shows the comparison of proteinuria decrease and the mean difference of
outcome achieved after antiviral therapy in each study.
The summary estimate for the mean difference of
proteinuria decrease at the end of therapy was 2.71 g/24
h (95% CI, 1.38–4.04, P < 0.0001) according to the random effects model. Using mean difference as the measure
of effect, the homogeneity test statistic yielded a P-value of
0.05, and the heterogeneity was I2 ¼ 53%.
Figure 3 shows the comparison of creatinine decrease
from baseline to after treatment. The pooled mean difference of creatinine decrease at the end of therapy was 0.23
mg/dL (95% CI 0.02–0.44, P ¼ 0.03) according to the
random effects model. Using mean difference as the measure of effect, the homogeneity test statistic yielded a
P-value of 0.30, and the heterogeneity was I2 ¼ 17%.
Summary estimates of outcomes between SVR and nonSVR subjects
The comparison between SVR and non-SVR groups is
shown in Figures 4 and 5. Only six studies compared proteinuria or creatinine decrease between the two groups, and,
among them, four studies were case reports [10, 19, 26, 27].
These cases had similar clinical features. Therefore, their
data was grouped and analysed as a whole study, and the
forest plots in Figures 4 and 5 only show three studies.
B. Feng et al.
According to the random effects model, the summary
estimate for the mean difference of proteinuria decrease
was 1.04 g/24 h (95% CI 0.20–1.89, P ¼ 0.02) in patients
who achieved SVR. Using mean difference as the measure
of effect, the homogeneity test statistic yielded a P-value of
0.21, and the heterogeneity was I2 ¼ 36% (Figure 4). The
comparison of creatinine decrease between SVR and nonSVR groups is shown in Figure 5. The pooled mean
difference of blood creatinine decrease in SVR patients
was 0.05 mg/dL (95% CI, 0.33 to 0.43, P ¼ 0.80). Using
mean difference as the measure of effect, the homogeneity
test statistic yielded a P-value of 0.70, and the heterogeneity
was I2 ¼ 0%.
Discussion
Conventional treatment of patients with glomerulonephritis
frequently includes steroids, immunosuppressive agents and
sometimes plasmapheresis. For patients with HCVassociated glomerulonephritis, the preferred treatment
strategy of conventional treatment alone, antiviral approach
based on IFNa alone or combination therapy remains undefined [30]. Johnson et al. reported that oral steroids with
HCV-associated nephritis had no beneficial effect on kidney function, although it may have improved the purpura.
While pulse steroids were associated with improvement in
renal function, these patients remained HCV-RNA positive
[28]. One problem with steroids and immunosuppressive
therapy is the increase in HCV-RNA levels with its possible detrimental consequences on the underlying liver disease [31]. Cyclophosphamide was successfully used for
treatment of HCV-infected patients with cryoglobulinaemia and progressive loss of kidney function due to MPGN,
but the HCV–RNA levels increased in these patients [32].
It has been suggested that in infected individuals, immunosuppressive therapy after kidney transplantation could be
associated with worsening of HCV liver disease [8].
In a prior meta-analysis of antiviral with immunosuppressive therapy for HCV-associated glomerulonephritis, it was
shown that standard IFNa therapy was more effective than
immunosuppressive therapy in lowering proteinuria of
patients with HCV-associated glomerulonephritis, whereas
serum creatinine levels were not affected by either therapy
[33]. However, the studies selected in this meta-analysis included patients who received immunosuppressive agents
during antiviral treatment, making it difficult to determine
the actual differential effect of each treatment alone. Additionally, variable antiviral regimens including inconsistent doses
and duration of treatment would be expected to have a negative impact on conclusions about the efficacy of IFNa. In
order to avoid these problems, the present meta-analysis compares results before to after stable regimens of antiviral
therapy in subjects with HCV-associated glomerulonephritis
and compares the results of those subjects who achieved SVR
to those who failed to do so (no SVR).
Despite the increased number of reported clinical studies
of antiviral treatment of HCV-associated glomerulonephritis, the actual number of patients studied remains relatively
small [33]. In this meta-analysis, the number of subjects in
each of the 11 selected studies ranged from 3 to 53 patients
Treatment of HCV-associated glomerulopathy
643
Table 1. Characteristics of included studies
Authors
Patients, n
(total/treated)
Country
Publication
year
Study design
Lost or terminated
antiviral therapy
Abbas et al. [25]
Alric et al. [7]
Beddhu et al. [26]
Bruchfeld et al. [27]
Garini et al. [10]
Johnson et al. [28]
Komatsuda et al. [29]
Mazzaro et al. [23]
Misiani et al. [9]
Rossi et al. [19]
Sabry et al. [12]
30/27
25/18
17/11
7/7
4/4
34/14
19/5
13/7
53/27
3/3
20/20
Pakistan
France
USA
Sweden
Italy
USA
Japan
Italy
Italy
Italy
Egypt
2008
2004
2002
2003
2007
1994
1996
2000
1994
2003
2002
Prospective, (cohort) study
Prospective, controlled
Retrospective, controlled
Retrospective
Retrospective, case series
Retrospective, controlled
Retrospective, controlled
Case controlled
Prospective randomized, controlled
Case series
Prospective
3
0
0
1
0
3
0
1
4
0
0
Table 2. Baseline characteristics of treated subjects enrolled in the selected studiesa
Men
(n, %)
Authors
Age
Abbas et al. [25]
Alric et al. [7]
36.0 6 9.0
54.8 6 16.0
60.0
68.0
Beddhu et al. [26]
Bruchfeld et al. [27]
Garini et al. [10]
Johnson et al. [28]
Komatsuda et al. [29]
Mazzaro et al. [23]
Misiani et al. [9]
Rossi et al. [19]
Sabry et al. [12]
Summary
43.3 6 4.3
47 (43–70)
54.3 6 17.0
46 (36–80)
49.2 6 11.0
64.0 6 12.0
62 (37–70)
51.0 6 13.9
NR
36.0 6 9.0 to
64.0 6 12.0
64.7
57.1
50.0
57.1
68.7
NR
15.1
66.7
65.0
15.1–
68.0%
HCV
genotype (GT)
Proteinuria
(g/24 h)
Serum
creatinine (mg/dL)
3a (most)
GT1:11; GT2:3;
GT3:2; GT4: 2
NR
GT1: 1; GT2: 3; GT3: 3
GT1: 4
NR
NR
GT1: 3; GT2: 4; GT3: 0
NR
GT2: 3
NR
GT1: 19; GT2: 13;
GT3: 32; GT4: 2; NR: 77
4.83 (1.6–9.07)
3.1 6 2.2b
1.44 (0.7–4.6)
1.33 6 0.46
6.5 6 6.1
4.0 6 3.6c
6.7 6 3.4
5.8 6 4.1
5.52 6 1.27
5.3 6 3.1
NR
3.47 6 1.59
4 (3.04–4.77)
3.1 6 2.2 to
6.7 6 3.4
1.69 6 0.43
NR
1.3 6 0.4
2.0 6 0.7
0.94 6 0.25
1.760.4
1.3 (0.7–3.5)
NR
1.2 (1.01–1.67)
0.94 6 0.25 to
2.0 6 0.7
a
NR, not reported.
In the Alric study, 18 treated patients received a two-phase treatment. Patients were treated first for nephrotic-range proteinuria with furosemide and
angiotensin converting enzyme inhibitor. After 4–12 weeks, all of them received anti-HCV combination therapy. Shown here is the mean value before the
primary therapy, and however, in Figure 2, the pretreatment mean value of 1.98 for proteinuria is that before anti-HCV therapy.
c
Derived from individual proteinuria values supplied in reference [30].
b
Table 3. Schedules of antiviral therapy in the selected studiesa
Authors
Antiviral agent
IFN dose
Therapy duration
Abbas et al. [25]
IFN-a 1 RBV
At least 24 weeks
Alric et al. [7]
Johnson et al. [28]
Komatsuda et al. [29]
Mazzaro et al. [23]
Misiani et al. [9]
IFNa (14) or Peg-IFNa 1
RBV (4)
IFNa
IFNa (5) or Peg-IFNa 1
RBV (2)
IFNa 1 RBV (2) or
Peg-IFNa 1 RBV (2)
IFNa
IFNa
Lymphoblastoid-IFN
IFNa-2a
Rossi et al. [19]
Sabry et al. [12]
IFNa 1 RBV
IFNa 1 RBV
3MU 3/week, RBV
200–1000 mg/day
3MU 3/week1.5 lg/kg/week,
RBV 600–1000 mg/day
3MU 3/week
3MU 3/week, 1.0 lg/kg/week,
RBV 200–800 mg/day
3MU 3/week, RBV 15 mg/kg/day,
80–100 lg/kg, RBV 800–1000 mg/day
3MU 3/week
6MU 7/week
3MU 3/week
1.5MU 3/week 3 1 week;
3 MU 3/week 3 23 week
3MU 3/week, RBV 15 mg/kg/day
3MU 3/week, RBV 15 mg/kg/day
Beddhu et al. [26]
Bruchfeld et al. [27]
Garini et al. [10]
a
RBV, ribavirin.
24–96 weeks
Patients, n
(SVR/no SVR)
4/26
12/6
48 weeks
Genotype 2 or 3: 24 weeks;
Genotype 1: 60 weeks
24–48 weeks
1/10
5/2
24–48 weeks
24 weeks
24wk
24 weeks
6/5
0/5
1/6
2/25
48 weeks
48 weeks
3/0
5/15
3/1
644
B. Feng et al.
Fig. 2. Forest plot of proteinuria evolution from baseline after antiviral treatment.
Fig. 3. Forest plot of creatinine evolution from baseline after antiviral treatment.
Fig. 4. Forest plot of the comparison of proteinuria evolution between patients with SVR and those with non-SVR.
Fig. 5. Forest plot of the comparison of blood creatinine evolution between patients with SVR and those with non-SVR.
(Table 1). In fact, when we divided the patients into SVR
and non-SVR groups, the number of cases in some studies
was too small for statistical analysis. Therefore, four of the
case series were pooled into a ‘mixpaper’ for the purpose of
comparing outcomes between SVR and non-SVR group
[10, 19, 26, 27].
Our meta-analysis shows that antiviral treatment based on
IFNa can decrease protein excretion or creatinine levels in
CKD patients infected with HCV. Following antiviral treatment, protein excretion decreased significantly [mean difference, 2.71 g/24 h; (95% CI 1.38–4.04, P < 0.0001)]. Serum
creatinine levels also decreased significantly [mean difference, 0.23 mg/dL; (95% CI 0.02–0.44, P ¼ 0.03)] at the end
of therapy, according to the random effects model (Figures 2
and 3). Because of reporting median data only, four studies
were not included in the analysis, but they made the same
Treatment of HCV-associated glomerulopathy
conclusion that antiviral therapy helped alleviate proteinuria,
which supports the result of the present meta-analysis on
protein excretion decrease by IFN therapy [9, 12, 25, 29].
In addition, three of the four excluded studies stated that
IFNa did not improve the creatinine levels, except for Misiani’s report [9], which may affect the pooled result of blood
creatinine decrease after antiviral treatment.
The improvement in protein excretion following antiviral
therapy was linked to HCV RNA clearance. Comparison
between non-SVR and SVR groups demonstrated that protein excretion decreased significantly in subjects who
achieved SVR [mean difference, 1.04 g/24 h; (95% CI
0.20–1.89, P ¼ 0.02)]; however, a significant decrease in
blood creatinine was not observed in the SVR group [mean
difference, 0.05 mg/dL (95% CI 0.33 to 0.43, P ¼ 0.80)]
(Figures 4 and 5). Fabrizi et al. [33] suggest that decreased
proteinuria per se at the end of antiviral treatment can reduce
or prevent the decline of glomerular filtration over time in
patients with HCV-associated glomerulonephritis (GN).
However, an additional mechanism whereby viral clearance
improves kidney disease remains to be determined. This can
be attributed to the suppression of circulating immune complexes in chronic infection and its associated B-lymphocyte
cryoglobulin production both of which account for the
HCV-induced glomerular injury [7, 8].
Additionally, HCV genotypes affect responses to IFN
treatment. In the seven studies, HCV genotype was
determined to decide dose and duration of therapy, but there
were no data about the association between HCV genotype
and HCV-related glomerulonephritis or that of achieving
SVR. As such, these issues cannot be addressed in this
analysis but do not seem to influence the conclusion that
response patterns of antiviral therapy can change levels of
proteinuria and creatinine.
The treatment of choice for chronic hepatitis C (CHC) is
IFNa combined with ribavirin [15]. As shown in general
CHC patients [15], ribavirin can significantly improve SVR
in HCV-associated glomerulonephritis in this analysis.
Among the patients with IFN plus ribavirin combination
therapy achieved a higher SVR than those with IFN monotherapy (32/82 versus 10/61, v2 ¼ 8.636, P ¼ 0.0033)
regardless of HCV genotype, type of IFN and antiviral
therapy duration. Alric et al. [7] observed a high rate of
SVR (66.7%) with combination therapy, although half of
their patients were infected with HCV genotype 1. Compared with IFN monotherapy, the major side effect of
combination treatment was ribavirin-induced hemolytic
anemia, which necessitated reduction of ribavirin dose or
the use of erythropoietin in a few patients. No patient required discontinuation of antiviral treatment because of
this.
As with most meta-analyses, there are limitations to the
present study. A major one is the small number of study
subjects making it difficult to perform subgroup analysis
on the basis of cryoglobulinemia, baseline proteinuria,
baseline creatinine level, pathological pattern of CKD, the
presence of hypertension or diabetes mellitus or concomitant
immunosuppressants. Another limitation is the lack of
randomized controlled trials (RCTs) of IFNa-based therapy
in HCV-associated GN. In addition, the included papers did
not specify whether patients received concomitant therapy
645
able to reduce proteinuria such as ACE-inhibitors or angiotensin-receptor blockers. However, the link between SVR
and reduction of proteinuria in this meta-analysis supports
a causal link between antiviral therapy per se and the
evolution of proteinuria. Only one of the 11 studies in this
analysis was an RCT [9]. Importantly, the analysed data
is on outcomes achieved upon completion of therapy,
whereas improvement of kidney function is a long process.
Regrettably, there are no long-term follow-up studies on
treated patients. Whether antiviral treatment based on IFNa
can delay or reverse the progress of CKD in the long run
remains unknown. Longer duration of follow-up, and kidney
biopsies would be needed to adequately evaluate the
outcomes. Further, larger RCTs using regular treatment with
standard or pegylated IFNa on HCV-related glomerulopathy
are required.
In conclusion, antiviral therapy based on IFNa can
significantly decrease proteinuria in patients with HCVassociated glomerulonephritis. The improvement in protein excretion is linked to HCV RNA clearance as the
treatment effect was greater in patients achieving SVR than
in those without SVR. Serum creatinine levels are not significantly improved whether obtaining SVR or not, but
stabilization of serum creatinine is achieved with IFNabased treatment. These results suggest that patients with
HCV-associated glomerulonephritis should receive antiviral therapy with the aim of achieving SVR and alleviating
CKD.
Acknowledgements. This work was supported by National S&T Major
Project for Infectious Diseases Control (grant nos. 2008ZX10002-012
and 2008ZX10002-013), Major State Basic Research Development Program of China (grant nos. 2005CB522902 and 2007CB512900), National
High-tech R&D Program of China (grant no. 2006AA02A410) and Peking
University People’s Hospital Research and Development Funds (grant no.
RDB2009-16).
Conflict of interest statement. None declared.
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Received for publication: 3.1.11; Accepted in revised form: 4.4.11