Hepatitis C virus & chronic kidney diseases
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Transcript of Hepatitis C virus & chronic kidney diseases
HCV & chronic renal diseases
Samir Haffar M.D.
Associate Professor of Gastroenetrology
Faculty of Medicine – Damascus – Syria
24th Congress of the SSGE – May 25-28, 2010 Dedeman Hotel – Lattakia – Syria.
HCV & chronic kidney diseases
• HCV diagnosis in CKD Patients
• HCV-related glomerulonephritis
• HCV in dialysis patients
• HCV and kidney transplantation
Testing of chronic hepatitis C
• anti-HCV (EIA*-3) Initially
• HCV RNA (RT-PCR**) Document viremia
• HCV genotyping Before treatment
* ELISA: Enzyme-Linked Immuno-Assay** RT-PCR: Real time Polymerase Chain Reaction
HCV diagnosis in dialysis patients2,653 patients
2 108 HD – 545 CAPD39 of 49 dialysis centers in the Netherlands
Anti-HCV (EIA-3)
79 patients +
HCV RNA +
57 patients +
2574 patients –
HCV RNA in pools of five
6 patients +
False negative 0.23%
Schneeberger PM et al. J Clin Microbiol 1998;36:1711–1715.
HCV-RNA test should be obtained prior to HD
• Heparin used during dialysis can interfere with the
PCR technique
• HD can lower HCV RNA by adsorption of HCV RNA
onto inner surface of dialyzers & destruction of viral
particles by hydraulic pressure exerted by blood
Okuda K et al. Lancet 1999;347:909–910.
Percutaneous liver biopsy in CHC with ESRD
Pawa S et al. Clin Gastroenterol Hepatol 2007;5:1316–20.
319 patients with CHC
Platelet, PT & PTTNo bleeding time
No arginine vasopressin
241 control patientsCHC without renal failure
5 complications3 severe2.1%
78 patients CHC & ESRD
1 complicationModerate
1.3%
Accuracy of fibrotest* in HD patients with CHC
*Noninvasive method to assess liver fibrosis in HCV on scale from 0 to 1Varaut A et al. Transplantation 2005 Dec 15;80:1550–5 .
110 CHC60 renal transplant recipients
50 hemodialysis patients
METAVIR scoreFibrotest
50 patients had fibrosis F2
AUROC for significant fibrosis Global population: 0.66
Hemodialysis patients: 0.47Renal transplant patients: 0.71
Liver stiffness for each Metavir stage in CHC
Box-and-whiskers plot
Vertical axis in logarithmic scale (wide range of F4 values)
Ziol M et al. Hepatology 2005 ; 41 : 48 – 54.
Prospective multicenter study 327 patients
Castera L et al. Gastroenterology 2005;128:343–350.
Prospective study 183 patients
HCV & chronic kidney diseases
• HCV diagnosis in CKD Patients
• HCV-related glomerulonephritis
• HCV in dialysis patients
• HCV and kidney transplantation
HCV-related glomerulonephritis
• Membranoproliferative glomerulonephritis (MPGN)
• IgA nephropathy
• Postinfectious glomerulonephritis
• Membranous nephropathy
• Thrombotic microangiopathies
• Focal & segmental glomerulosclerosis
• Fibrillary glomerulopathy
Perico N et al. Clin J Am Soc Nephrol 2009;4:207–220.
Cryoglobulinemia Systemic vasculitis of small-calibre arteries & veins
Type Frequency Associated disease
Type ISingle
10 – 15 % Monoclonal Lymphoproliferative disorderIndistinguishable from MM, Waldenströ ِm, or CLL
Type IIMixed
50 – 60% MixedMonoclonal & polyclonal
HCV
Type IIIMixed
30 – 40% MixedMonoclonal & polyclonal
Connective tissue disease Autoimmune diseasesChronic bacterial infectionsChronic viral infections
Incidence of CHC in Mixed Cryoglobulinemia 40 – 100% 90% in Mediterranean basin
Sansonno D et al. Lancet Infect Dis 2005; 5: 227–36
Prevalence of cryoglobulinemia in CHCMeta-analysis
• No of studies 19 studies between 1994 & 2001
• No of patients 2 323 patients
• Cryoprecipitate 1 022 patients prevalence 44%
• Cirrhosis 40% of patients with cryoprecipitate
17% of patients without cryoprecipitate
OR for cirrhosis in CP*+: 4.87 (3.3-7.1)
* CP: CryoprecipitatesKayali Zeid et al. Hepatology 2002;36:978-985.
Cryoglobulins may be useful indicator
for increased risk of cirrh
osis in CHC
Signs & symptoms in mixed cryoglobulinemia• Skin Palpable purpura 90%
Leg ulcers 15%
Raynaud’s phenomenon 30%
Cold urticaria 10%• Liver Hepatomegaly 70%
Hypertransaminasaemia 50%• Kidney Microscopic hematuria 30%
Proteinuria 15%
Arterial hypertension 40%• MS system Arthralgia 70%
Asthenia 80%• NS Peripheral: Motor-sensory axonopathy 60%
Acute mononeuritis 5%
Central Neurocognitive impairment 25%
Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
Any organ may be affected
Palpable purpura
Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
Most frequent sign of MC: 90%
Usually the first sign of MC
Raise immediate suspicion of MC
Chronic leg ulcersRelatively frequent
Above the malleoli
Always associated with purpura
Absence of severe stasis dermatitis
Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
Mixed Cryoglubulinemia in CHCMajority of patients have no or nonspecific symptoms
• Meltzer's triad (30%): purpura, asthenia, arthralgia
• Most frequent affected tissues: skin, nerves, & kidney
• Renal involvement (1/3 of patients)
Signs Proteinuria – microhematuria – RI – HTN
Diagnosis Positive anti-HCV & HCV RNA
Biopsy MPGN with immune complex deposition
Renal biopsy of cryoglobulinaemic patient
Immunohistochemical detection of HCV coreprotein in glomerular vascular structures
Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
Association between HCV & ESRDRetrospective cohort study
Medicare, Department of Veterans Affairs, & US Renal Data SystemCreatinine measured between Oct 2000 & Sept 2001
2 352 584 patients
3 years follow-up – ESRD
Tsui JI et al.Arch Intern Med. 2007;167:1271-1276.
Anti-HCV –421 495patients (89%)
3.05/ 1000 person-years 95% CI: 2.96 – 3.14
Anti-HCV +52 874 patients (11%)
4.26 /1000 person-years95% CI: 3.97 – 4.57
anti-HCV test within 1 year of creatinine testing474 369 patients
HCV & chronic kidney diseases
• HCV diagnosis in CKD Patients
• HCV-related glomerulonephritis
• HCV in dialysis patients
• HCV and kidney transplantation
Prevalence of HCV in long-term dialysis patients Developing countries
Country Anti-HCV positives Reference year
Brazil 16.4% (180/1095) 2007
Turkey 19% (83/437) 2005
Tunisia 20% (79/395) 2006
Sudan 23.7% (56/236) 2007
Iran 24.8% (74/298) 2005
Saudi Arabia 43.4% (86/198) 2004
Moldavia 75% (111/148) 1999
Morocco 76% (141/186) 2005
Egypt 80% (169/210) 2000Martin P et al. J Hepatol 2008;49:613–624.
DOPPSProspective observational study – Based on anti-HCV
• Facilities 308 representative dialysis facilities• Patients 8615 hemodialysis patients• Countries 7 countries from 3 continents
France, Germany, Italy, Japan, Spain, US
• Time 1997-98 to 2001• Prevalence Mean 13.5% (2.6 – 22.9%)• Seroconversion 56% of facilities: no seroconversion
44% of facilities: > 0 – 20%DOPPS: Dialysis Outcomes & Practice Patterns Study
Fissell RB et al. Kidney Int 2004;65:2335–2342.
HCV prevalence & time on dialysis
Fissell RB et al. Kidney Int 2004;65:2335–2342.
Impact of HCV on survival in dialysis patientsMeta-analysis
• No of studies 7 studies (5 cohorts – 2 case-controls)
• No of patients 11 589 patients on maintenance dialysis
• RR for death 1.34 (95% CI: 1.13-1.59)
Heterogeneity statistics, R(i) = 0.48
P-value by Q-test = 0.13
• Cause of death Liver cirrhosis & HCC more frequent
Fabrizi F et al J Viral Hepat 2007;14:697–703.
Excess risk of death in HCV-positive
patients on HD partially attributed to CLD
HCV & death risk in hemodialysis patients82 933 patients on MHD for at least 45 days
3 year period: 2001 – 2004580 outpatient dialysis facilities of DaVita Inc*
* DaVita Inc: Large dialysis organizationKalantar-Zadeh K et al. J Am Soc Nephrol 2007;18:584–1593.
anti-HCV EIA at least once
13 664 patients
1590 patients (12%)
anti-HCV +
Mortality Hazard Ratio: 1.25 95% CI: 1.12 – 1.39 (P < 0.001)Higher all-cause & CV mortality
Preventing HCV transmission in HD units
• Wear disposable gloves when caring for patient
Remove gloves & wash hands between each patient
• Use disposable items
Nondisposable items dedicated for use on single patient
Unused medications dedicated for use on single patient
• Separation of clean & contaminated areas
• Clean & disinfect dialysis station between patients
e.g., chairs, beds, tables, machines
Centers for Disease Control & Prevention MMWR Recomm Rep 2001;50:1-43.
Practice of hand hygiene in HD unitsOne person observed the staff in 9 dialysis units during 1 month
495 randomly distributed 30 min observation periodsCovered all steps of hemodialysis session
Dolores Arenas M et al. Nephrol Dial Transplant 2005;20:1164–1171.
977 opportunities to wear gloves & wash hands following activity
Gloves used in 93% Hands washed in 36%
1902 opportunities to wash hands before activity
Hands washed in 148%
Higher patient-to-nurse ratio influenced hand washing before& after patient contact
Universal precautions prevent HCV transmission 963 patients – 15 Belgian units
No isolation of anti-HCV patientsAnti-HCV (EIA 2 or 3) every 18 m for 54 m
Jadoul M et al. Kidney Int 1998;53:1022-1025.
488 patients available
Drop-up from death or RT
1st 18 month (May 91 – Nov 92): 1.41 %
HCV seroconversion
2nd 18 month (Nov 92 – May 94): 0.56 %
Reinforced precautions
3rd 18 month (May 94 – Nov 95): 0 %
P=0.04
HCV & chronic kidney diseases
• HCV diagnosis in CKD Patients
• HCV-related glomerulonephritis
• HCV in dialysis patients
• HCV and kidney transplantation
Kidney transplantation for HD patients with CHC
Anti-HCV positive patient on dialysis0
HCV RNA –
Waiting list for KT
Normal LFTs
Kidney transplantation for HD patients with CHC
Anti-HCV positive patient on dialysis0
Liver failure
Liver & kidney transplantation
Kidney transplantation for HD patients with CHC
Chronic hepatitis
IFN
HCV RNA – HCV RNA +
Anti-HCV positive patient on dialysis0
Cirrhosis
Liver & kidney transplantation
HCV RNA +
Liver biopsy
Waiting list for KT
Normal
Thank You
HCV genome
Sansonno D et al. Lancet Infect Dis 2005 ; 5 : 227 – 36.
• Anti-HCV (ELISA)
1st generation Frequent false-negative results
2nd generation Frequent false-negative results
3rd generation Rare false-negative results
(6/2576 pts - 0.23% )• RIBA testing Surpassed by PCR technology• HCV-RNA Obtained prior to HD procedure• Heparin can interfere with PCR
technique
Schneeberger PM et al. J Clin Microbiol 1998 ; 36 : 1711 – 1715.
KDIGOKidney Disease: Improving Global Outcomes
Epidemiology of HCV in dialysis population
Serological tests of chronic HCV infection
Rodés J et all. Textbook of hepatology: from basic science to clinical practice.Blackwell Publishing, Oxford, UK, 3rd edition, 2007
Cryoglobulinemia
Type Frequency Associated disease
Type ISingle
10 – 15 % Monoclonal Lymphoproliferative disorderIndistinguishable from MM, Waldenströ ِm, or CLL
Type IIMixed
50 – 60% MixedMonoclonal & polyclonal
HCV
Type IIIMixed
30 – 40% MixedPolyclonal & monoclonal
Connective tissue disease Autoimmune diseasesChronic bacterial infectionsChronic viral infections
Incidence of HCV infection in EMC 40–100% 90% in Mediterranean basin
Mixed Cryoglobulinemia
Josephsen G. N Engl J Med 2005;352:2627.
38-year-old woman
CHC treated with IFN- several years ago
Palpable lesions on legs & feet
HBsAg – & anti-HCV +
Acute renal failure & pancytopenia
Improvement with plasmapheresis
Kidney transplantation for HD patients with CHC
CirrhosisChronic hepatitis
IFN
HCV RNA – HCV RNA +
Anti-HCV positive patient on dialysis0
HCV RNA –
Waiting list for KT
Normal LFTs
Liver failure
Liver & kidney transplantation
HCV RNA +
Liver biopsy
Normal
Increased risk of HCV in HD patients
• Longer time on dialysis• Male gender• Black race• Diabetes• HBV infection• Prior renal transplantation• Alcohol or substance abuse in previous 12 month
Fissell RB et al. Kidney Int 2004;65:2335–2342.
Proposed model of cryoprecipitating immune complex in HCV-related cryoglobulinemia
Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
Practice of hand hygiene in hemodialysis units
• One person observed health care staff in 9 dialysis units495 randomly distributed 30 min observation periodsCovered all steps of hemodialysis session
Dolores Arenas M et al. Nephrol Dial Transplant 2005;20:1164–1171.
Tests no longer needed
• RIBA: Recombinant Immuno-Blot Assay
• Qualitative HCV RNA by PCR
Practice of hand hygiene in hemodialysis units
• One person observed health care staff in 9 dialysis units495 randomly distributed 30 min observation periodsCovered all steps of hemodialysis session
• 1902 opportunities to wash hands before patient contact• 977 opportunities to wear gloves •
Dolores Arenas M et al. Nephrol Dial Transplant 2005;20:1164–1171.
HCV & death risk in hemodialysis patients
Kalantar-Zadeh K et al. J Am Soc Nephrol 2007;18:584–1593.