Transcript Document

Burden, detection and
evaluation of HCV in
CKD patients
Dr Pankaj Hans
Patna
India: Kidney disease burden
 India is the world’s largest democracy
with a population of around 1.13 billion
and faces tremendous challenges to
provide basic healthcare for its masses
 The incidence rates of end-stage renal
disease (ESRD) in India

232 per million population (age adjusted
rate)
NDT Plus 2010; 3: 203–207
India: Kidney disease burden
 The Indian Chronic Kidney Disease
(CKD) registry is an initiative by the
Indian Society of Nephrology, and out of
the latest total of 35 697 CKD patients,


26 609 (74.5%) amongst the CKD patients
were not receiving any form of RRT (renal
replacement therapy) and
only 880 (2.5%) received renal
transplantation (RT)
NDT Plus 2010; 3: 203–207
India: Kidney disease burden
 It is estimated that >90% of patients with
ESRD in South Asia die within months of
diagnosis because they cannot afford
treatment
NDT Plus 2010; 3: 203–207
CKD Clinical Stages
Stage Description
GFR
(ml/min/1.73 m2)
1
Kidney damage with normal or ↑ GFR
 90
2
Kidney damage with mild  GFR
60-89
3
Kidney damage with moderate  GFR
30-59
4
Severe  GFR
15-29
5
Kidney Failure (ESRD)
< 15 (or dialysis)
CKD – A Silent Killer
CKD – Increased Death
CKD at a glance
 CKD – A Global Pandemic
 CKD 1-2 are asymptomatic
 Third after CVD, Cancer
 1 in 10 Indians have CKD
 10 million people of CKD
 Term ‘CRF’ no longer used
 Dialysis ↑ death rate 100 x
 Small ↑ in Creat - ↑ ↑ in CV
HCV - CKD
Screening for HCV in
hemodialysis
Introduction: HCV in CKD
 Hepatitis C virus (HCV) infection in
hemodialysis (HD) is a significant
problem
 Liver disease caused by HCV causes

The Hepatitis
C Virus.
Significant morbidity and mortality among
patients with end stage renal disease
(ESRD) treated with HD
Indian J Nephrol. 2009 April; 19(2): 62–67.
Burden HCV in CKD
 Prevalence of anti- HCV and chronic
HCV infection in dialysis units worldwide


Considerable variation
Ranging from
 As
low as 1% to
 As high as 95%
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Burden HCV in CKD
 Prevalence Hepatitis C in HD patients in

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Middle Eastern countries: 68%
Saudi Arabia: 14.5% to 94.7%
Oman : 26%
Egypt: 80%
Western Europe: 1%–29%
North America: 8%–36%
Australia: 5.9% , and
Far Eastern countries: 44%–60%
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Burden HCV in CKD
 With the introduction of routine screening
and heightened attention to prevention of
spread,


The incidence of HCV infection has
declined in dialysis centers in many
countries, but
Remained high in others
Kidney International, 1997;51(4): 981–99.
Burden HCV in CKD
 Currently, third-generation anti-HCV
ELISA is largely in use and has shown

Greater sensitivity and specificity in
patients receiving HD
 Using third-generation ELISA,
prevalence of anti-HCV antibodies
among dialysis patients was found to be

42% in France, 75% in Moldavia, and 49%
in Syria
Indian J Nephrol. 2009 April; 19(2): 62–67.
Burden HCV in CKD
 In the US,


The prevalence of hepatitis C in the
dialysis population has not changed, and
The incidence of new cases of hepatitis C
has remained constant, in the
 Range
of 1% to 3% per year
US Renal Data System: USRDS 2002 Annual Data Report
Burden HCV in CKD
 Indian study

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Single centre study
A total of 119 hemodialysis patients were
tested for HCV RNA
Results:
 Thirty
three (27.7%) tested positive
Indian J Nephrol. 2009 April; 19(2): 62–67.
Burden HCV in CKD
 Indian study

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Prevalence of HCV RNA in the HD
population is 27.7%
Important associations for HCV RNA
positivity
 Duration
of dialysis
 Getting dialysis at > 1 center
 Elevated transaminase levels, and
 Low serum albumin
Indian J Nephrol. 2009 April; 19(2): 62–67.
Burden HCV in CKD
 The high prevalence of HCV in dialysis
patients is of
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Great concern in view of studies that
suggest that
These patients have a higher mortality
than HCV-negative patients
Journal of the American Society of Nephrology, 2000; 11(10):1896–1902
Kidney International 1998; 53(5):1374–1381
Hepatitis C in Dialysis
 In a multicenter prospective study from
Japan,

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1,470 patients (19% positive for anti-HCV)
from 16 dialysis centers were followed up
for an average of 6 years
Mortality was greater in the anti- HCVpositive group (33%) than in controls
(23%)
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 The excess mortality appeared to be
accounted for by deaths from

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Cirrhosis (5.5% versus 0%) and
Hepatocellular carcinoma (8.8% versus
0.4%)
The RR for death in anti- HCV-positive
patients was 1.57 (95% CI, 1.23 to 2.00).
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 In a study from the US,
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287 anti-HCV positive and 286 randomly
selected dialysis control patients from 14
transplant centers were assessed, with a
median follow up of 7 years
In multivariate analysis, RR for death from
all causes in anti-HCV-positive patients
was 1.41 (95% CI, 1.01 to 1.97), and for
death from liver disease or infection, 2.39
(95% CI, 1.28 to 4.48)
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 Death from liver disease occurred in
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14% of anti-HCV–positive and only 2% of
anti-HCV–negative controls
These data show that
 Chronic
hepatitis C adversely affects survival
in patients with ESRD;

Cirrhosis and liver cancer account for 13%
to 14% of deaths
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 The spectrum of liver disease in HCV
positive HD patients
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Mild to moderate in most series, and a
High proportion of patients had normal ALT
levels
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 In studies, the frequency of bridging
hepatic fibrosis (stage 3) or cirrhosis
(stage 4) ranged from
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5% to 32%.
In most studies, there were no
associations between ALT or HCV RNA
levels and severity of histological changes
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 Risk factors for spread include a
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History of transfusions,
Number of blood products transfused, and
Number of years on hemodialysis
 Transmission of HCV, as with HBV,

Depends on the presence of chronically
infected patients and potential exposure to
blood and blood products
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Hepatitis C in Dialysis
 Although HCV transmission through
blood product transfusion was a
significant source of infection previously,

The current cases are more likely related
to nosocomial exposure
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
KDIGO guideline
 Guideline 1: Detection and evaluation of
HCV in CKD
 Determining which CKD patients should
be tested for HCV

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It is suggested that CKD patients be tested
for HCV (Weak evidence)
Testing for HCV should be performed in
patients on maintenance hemodialysis
(CKD Stage 5D) and kidney transplant
candidates. (Strong evidence)
Kidney International 2008; 73 (Suppl 109), S10–S19
Algorithm
CKD Stage 5
HD diagnostic
algorithm
 In particular, note that
after a negative primary
NAT, a patient can be
considered to be at low
probability of HCV
infection (unless other
factors change) so that
subsequent testing by EIA
is appropriate

ALT,alanine aminotransferase;
AST, aspartataminotransferase;
CKD: chronic kidney disease;
EIA: enzyme immunoassay;
HCV: hepatitis C virus;
 NAT: nucleic acid test.
Kidney International 2008; 73 (Suppl 109), S10–S19
KDIGO guideline
 Guideline 2: HCV testing for patients on
maintenance hemodialysis:
 Patients on HD should be tested when
they first start hemodialysis or when they
transfer from another hemodialysis
facility. (Strong evidence)
Kidney International 2008; 73 (Suppl 109), S10–S19
KDIGO guideline (Contd)
 Testing for HCV with NAT should be
performed for hemodialysis patients with
unexplained abnormal
aminotransferase(s) levels. (Strong
evidence)
 If a new HCV infection in a hemodialysis
unit is suspected to be nosocomial,
testing with NAT should be performed in
all patients who may have been
exposed. (Strong evidence)
Kidney International 2008; 73 (Suppl 109), S10–S19
KDIGO guideline (Summary)
 These strong recommendations should
be applicable worldwide, as

NAT: nucleic acid test
It is rare that a country or individual can
afford maintenance hemodialysis yet not
afford occasional HCV testing—at least by
means of HCV antibody measurement if
not NAT
Nature clinical practice NEPHROLOGY
Published online 23 September 2008
KDIGO guideline (Summary)
 These two techniques

HCV antibody testing and NAT
 Provide

similar epidemiological information,
Although HCV antibody measurement has
 Lower
accuracy than NAT and
 Cannot detect very early infection
Nature clinical practice NEPHROLOGY
Published online 23 September 2008
KDIGO guideline (Summary)
 The weaker recommendations regarding
HCV detection are less applicable in
many countries
 The suggestion that all patients with
CKD be tested for HCV is unlikely to be
followed since the number of such
patients is enormous
Nature clinical practice NEPHROLOGY
Published online 23 September 2008
KDIGO guideline (Summary)
 Other suggestions revolve around the

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Frequency of testing and
The use of NAT,
Both of which are subject to local factors
HCV in CKD
 In addition to standard universal
precautions, additional practices are
recommended because exposure to
blood is routinely anticipated
 These recommendations include

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Special dialysis unit precautions
Regular serological testing
Active surveillance, and
Training and education
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
HCV in CKD
 Recommended precautions include

Routine use of gloves and restriction of
use of common supplies, medications, and
carts to deliver them
 In addition, there should be

Strict attention to cleaning and disinfecting
items shared between patients and careful
disposal of dialyzers and blood tubing after
treatments.
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
HCV in CKD
 The CDC has not recommended
isolation of HCV-infected patients in
dialysis units
 Baseline testing should include

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Serum ALT levels and assays for both
HBV and HCV infection
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
HCV in CKD
 For anti-HCV-negative patients,
recommended monitoring includes

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Testing ALT levels monthly and
Anti-HCV every 6 months
Elevations in ALT levels should lead to
anti-HCV testing
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
HCV in CKD
 If ALT levels are persistently abnormal
despite the absence of anti-HCV, testing
for HCV RNA by

Qualitative assay (such as polymerase
chain reaction) should be considered
Hepatitis Research and Treatment
Volume 2010, Article ID 534327,
Conclusions
 CKD population is increasing in India
 HCV infection in HD patients is a
significant problem
 Prevalence of HCV RNA in the HD
population is 27.7% (according to Indian
study)
 Studies suggest higher mortality in HCV
positive patients than HCV-negative
patients in dialysis setup
Slide 1 of 3
Conclusions
 Testing for HCV should be performed
in patients on maintenance
hemodialysis (CKD Stage 5D) and
kidney transplant candidates
 Patients on HD should be tested when
they first start hemodialysis or when they
transfer from another hemodialysis
facility
Slide 2 of 3
Conclusions
 Testing for HCV with NAT should be
performed for hemodialysis patients with
unexplained abnormal
aminotransferase(s) levels
 HCV antibody testing and NAT


Provide similar epidemiological information,
Although HCV antibody measurement has
 Lower
accuracy than NAT and
 Cannot detect very early infection
Slide 3 of 3