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Hepatitis C virus & chronic kidney diseases

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Hepatitis C virus & chronic kidney diseases

  1. 1. 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.
  2. 2. HCV & chronic kidney diseases • HCV diagnosis in CKD Patients • HCV-related glomerulonephritis • HCV in dialysis patients • HCV and kidney transplantation
  3. 3. 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
  4. 4. HCV diagnosis in dialysis patients 2,653 patients 2 108 HD – 545 CAPD 39 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.
  5. 5. 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.
  6. 6. Percutaneous liver biopsy in CHC with ESRD Pawa S et al. Clin Gastroenterol Hepatol 2007;5:1316–20. 319 patients with CHC Platelet, PT & PTT No bleeding time No arginine vasopressin 241 control patients CHC without renal failure 5 complications 3 severe 2.1% 78 patients CHC & ESRD 1 complication Moderate 1.3%
  7. 7. Accuracy of fibrotest* in HD patients with CHC *Noninvasive method to assess liver fibrosis in HCV on scale from 0 to 1 Varaut A et al. Transplantation 2005 Dec 15;80:1550–5 . 110 CHC 60 renal transplant recipients 50 hemodialysis patients METAVIR score Fibrotest 50 patients had fibrosis  F2 AUROC for significant fibrosis Global population: 0.66 Hemodialysis patients: 0.47 Renal transplant patients: 0.71
  8. 8. 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
  9. 9. HCV & chronic kidney diseases • HCV diagnosis in CKD Patients • HCV-related glomerulonephritis • HCV in dialysis patients • HCV and kidney transplantation
  10. 10. 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.
  11. 11. Cryoglobulinemia Systemic vasculitis of small-calibre arteries & veins Type Frequency Associated disease Type I Single 10 – 15 % Monoclonal Lymphoproliferative disorder Indistinguishable from MM, Waldenström, or CLL Type II Mixed 50 – 60% Mixed Monoclonal & polyclonal HCV Type III Mixed 30 – 40% Mixed Monoclonal & polyclonal Connective tissue disease Autoimmune diseases Chronic bacterial infections Chronic 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
  12. 12. Prevalence of cryoglobulinemia in CHC Meta-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: Cryoprecipitates Kayali Zeid et al. Hepatology 2002;36:978-985.
  13. 13. 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.
  14. 14. 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
  15. 15. Chronic leg ulcers Relatively frequent Above the malleoli Always associated with purpura Absence of severe stasis dermatitis Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
  16. 16. Mixed Cryoglubulinemia in CHC Majority 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
  17. 17. Renal biopsy of cryoglobulinaemic patient Immunohistochemical detection of HCV core protein in glomerular vascular structures Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
  18. 18. Association between HCV & ESRD Retrospective cohort study Medicare, Department of Veterans Affairs, & US Renal Data System Creatinine 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-years 95% CI: 3.97 – 4.57 anti-HCV test within 1 year of creatinine testing 474 369 patients
  19. 19. HCV & chronic kidney diseases • HCV diagnosis in CKD Patients • HCV-related glomerulonephritis • HCV in dialysis patients • HCV and kidney transplantation
  20. 20. 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) 2000 Martin P et al. J Hepatol 2008;49:613–624.
  21. 21. DOPPS Prospective 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.
  22. 22. HCV prevalence & time on dialysis Fissell RB et al. Kidney Int 2004;65:2335–2342.
  23. 23. Impact of HCV on survival in dialysis patients Meta-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.
  24. 24. HCV & death risk in hemodialysis patients 82 933 patients on MHD for at least 45 days 3 year period: 2001 – 2004 580 outpatient dialysis facilities of DaVita Inc* * DaVita Inc: Large dialysis organization Kalantar-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
  25. 25. 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.
  26. 26. Practice of hand hygiene in HD units One person observed the staff in 9 dialysis units during 1 month 495 randomly distributed 30 min observation periods Covered 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
  27. 27. Universal precautions prevent HCV transmission 963 patients – 15 Belgian units No isolation of anti-HCV patients Anti-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
  28. 28. HCV & chronic kidney diseases • HCV diagnosis in CKD Patients • HCV-related glomerulonephritis • HCV in dialysis patients • HCV and kidney transplantation
  29. 29. Kidney transplantation for HD patients with CHC Anti-HCV positive patient on dialysis0 HCV RNA – Waiting list for KT Normal LFTs
  30. 30. Kidney transplantation for HD patients with CHC Anti-HCV positive patient on dialysis0 Liver failure Liver & kidney transplantation
  31. 31. 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
  32. 32. Thank You
  33. 33. HCV genome Sansonno D et al. Lancet Infect Dis 2005 ; 5 : 227 – 36.
  34. 34. • 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.
  35. 35. KDIGO Kidney Disease: Improving Global Outcomes
  36. 36. Epidemiology of HCV in dialysis population
  37. 37. 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
  38. 38. Cryoglobulinemia Type Frequency Associated disease Type I Single 10 – 15 % Monoclonal Lymphoproliferative disorder Indistinguishable from MM, Waldenström, or CLL Type II Mixed 50 – 60% Mixed Monoclonal & polyclonal HCV Type III Mixed 30 – 40% Mixed Polyclonal & monoclonal Connective tissue disease Autoimmune diseases Chronic bacterial infections Chronic viral infections Incidence of HCV infection in EMC 40–100% 90% in Mediterranean basin
  39. 39. 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
  40. 40. 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
  41. 41. 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.
  42. 42. Proposed model of cryoprecipitating immune complex in HCV-related cryoglobulinemia Sansonno D et al. Lancet Infect Dis 2005;5:227–36.
  43. 43. Practice of hand hygiene in hemodialysis units • One person observed health care staff in 9 dialysis units 495 randomly distributed 30 min observation periods Covered all steps of hemodialysis session Dolores Arenas M et al. Nephrol Dial Transplant 2005;20:1164–1171.
  44. 44. Tests no longer needed • RIBA: Recombinant Immuno-Blot Assay • Qualitative HCV RNA by PCR
  45. 45. Practice of hand hygiene in hemodialysis units • One person observed health care staff in 9 dialysis units 495 randomly distributed 30 min observation periods Covered 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.
  46. 46. HCV & death risk in hemodialysis patients Kalantar-Zadeh K et al. J Am Soc Nephrol 2007;18:584–1593.

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