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Nephrology Case Conference

Nephrology Case Conference. 報告日期 : 2011/10/05 指導老師 : 方基存教授 報告醫師 : R3 陳惠湘. Side effects of antiviral treatment. HCV Treatment in CKD patient. HCV and CKD. Review the case. Case Presentation. Discussion. Outlines. Case Presentation.

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Nephrology Case Conference

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  1. Nephrology Case Conference 報告日期: 2011/10/05 指導老師: 方基存教授 報告醫師: R3 陳惠湘

  2. Side effects of antiviral treatment HCV Treatment in CKD patient HCV and CKD Review the case Case Presentation Discussion Outlines Company Logo

  3. Case Presentation

  4. Patient Profiles • Name: 徐O緯 • Gender: Male • Birthday: 1954/08/25 (57y/o) • Ethnic: Taiwanese • Occupation: sales, retired • Marital status: married • Traveling history: nil • Admission during 2011/04/23~2011/04/29 at GI ward Company Logo

  5. Chief Complaint • Progressive depressive mood and behavior change since about one month ago Company Logo

  6. Present Illness -1 • This 57 y/o male patient is a case with histories of ESRD under regular HD and HCV carrier who follow up at our GI OPD. • Since one month before admission, he was noted with agitation, depressive mood, insomnia and suicide ideation. • According to his wife, he has received Interferon + Ribavirin treatment for hepatitis C since about one and half month ago. Company Logo

  7. Present Illness -2 • He denied constipation and high protein diet. No bloody or tarry stool noted, no fever checked. • No other medication taken except those from OPD. • General malaise but no focal limb weakness. Company Logo

  8. Past history • End stage renal disease under regular hemodialysis via left AVG for about 13 years • Hepatitis C carrier • Known when screening for HD • History of tooth retraction with bleeding, blood transfusion(+) • Secondary hyperparathyroidism status post total parathyroidectomy with autotransplantation in 2008 • Nephrolithiasis • Hypertension known for 13 years Company Logo

  9. Personal history • Allergy: no known allergy history • Smoking: denied • Alcohol: denied • Betel nut: denied Company Logo

  10. Family history • Family history: Colon cancer GN Company Logo

  11. Physical Examination -1 • Vital signs: • BT:36.3’C, BP:120/82mmHg, HR:75/min, RR:16/min • General appearance: chronic ill looking • Consciousness: oriented, E4V5M6 • HEENT: • Conjunctiva: pale, Sclera: anicteric • Neck: no stiffness, no lymphadenopathy • Chest: • Smooth respiratory pattern • Breathing sound: bilateral coarse • Heart sound: regular heart beat, murmur(-) Company Logo

  12. Physical Examination -2 • Abdomen: • soft, no tenderness • normoactive bowel sound • Bruit(?) • Extremities • Freely movable • No pitting edema • Left AVG bruit/thrill(?) • Skin: • Intact, no rashes Company Logo

  13. Lab data when admitted (4/22-4/23) • Leukopenia with lymphopenia • Thrombocytopenia • Normocytic anemia Company Logo

  14. Lab data when admitted (4/22-4/23)  68 (4/23)  68 (4/25) Company Logo

  15. CXR (4/22) • No definite active lung lesion Company Logo

  16. Brain CT (4/22) • No definite evidence of infarction Company Logo

  17. Current medications at OPD • 2011/2/15 Nephrology OPD: • Fosinopril(10mg) 0.5# QD • Silymarin(150mg) 1# QD • Carvedilol(6.25mg) 0.5# QD • 2011/4/11 GI OPD • Ribavirin(200mg) 1# QD • Peginterferon alfa-2b(100mcg) 1pc QW • Mefenamic acid(250mg) 1# QID • 2011/04/20 HD room • Epoetin beta (2000iu) 1pc TIW • Atenolol(100mg) 1# QD Company Logo

  18. Impression • Suspect Interferon induced mood disorder • Leukopenia/Thrombocytopenia and Anemia, suspect Interferon/Ribavirin related • ESRD under hemodialysis • HCV carrier • Secondary hyperparathyroidism status post total parathyroidectomy with autotransplantation • Nephrolithiasis Company Logo

  19. Admission course -1 c/s Psychi doctor 1st suicide at ER 2nd suicide at ward Hold IFN+RBV since 4/22 (s/p 6th injection) Company Logo

  20. Admission course -2 Company Logo

  21. Review this patient’s history HCV-RNA 0.006 million IU/ml HCV-RNA 15.2 million IU/ml HCV-RNA (-) HCV-RNA (-) HBV(-) Genotype 1b PegIFN 100mcg/QW P’t want to withdraw the Tx… RBV 200mg 3#BID RBV 200mg 1#QD EPO 2000iu TIW 5000 Company Logo

  22. HCV and CKD

  23. Epidemiology of HCV • Hepatitis C virus is a blood-borne pathogen that appears to be endemic in most parts of the world. • WHO estimates that the global prevalence of HCV infection averages 3%, or around 170 million infected persons worldwide. World J Gastroenterol 2007 May 7; 13(17): 2436-2441 Company Logo

  24. Epidemiology of HCV in CKD P’t -1 • The reported prevalence of HCV infection in haemodialysis units of developed countries has ranged from 2.6-22.9% (with a mean of 13.5%) • But prevalence may be as high as 70% in developing countries. Postgrad Med J 2010;86:486-492 Company Logo

  25. Epidemiology of HCV in CKD P’t -2 • High rate of HCV transmission among CKD patients • direct exposure to infectious blood and/or blood products because of inadequate infection control. • improving since 1992 with regular screening • Cross contamination between patients can occur in dialysis units • lack of disinfection of commonly utilised medication equipment and supplies • the use of shared vials of heparin • blood spills which are not immediately cleaned Postgrad Med J 2010;86:486-492 Company Logo

  26. Natural history of HCV in CKD P’t -1 • ALT values may not be a useful indicator of liver damage among CKD patients • Suppression of ALT synthesis in hepatocytes, inhibition of its release into the bloodstream and accelerated clearance from serum have been proposed as probable mechanisms of low ALT values in CKD patients • Liver biopsy may be required for CKD patients to assess the degree of liver damage and to plan antiviral therapy. • Transjugular biopsy • Elastography Postgrad Med J 2010;86:486-492 Company Logo

  27. Natural history of HCV in CKD P’t -2 • In renal transplant patient • renal transplant recipients with HCV infection had higher mortality rates (RR 2.23) • graft losses were higher (RR 1.96) • Risk for development of post-transplant diabetes mellitus and MGN was also higher Postgrad Med J 2010;86:486-492 Company Logo

  28. HCV vs. CKD • Chronic infection with hepatitis C could be both the main cause and the complication of CKD. • Probable association between HCV infection and renal disease was first reported in 1990.  Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis 1990;162:569-70 Company Logo

  29. HCV vs. CKD -- associated • Study Design: National cohort study. • Setting & Participants: HCV-infected and -uninfected veterans in ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) in 2001-2006. • Outcomes: Incident CKD stages 3-5. • Conclusions: HCV infection is associated with higher risk and shorter time to CKD despite having a lower prevalence of many CKD risk factors. HCV-infected persons should have targeted monitoring for the development and progression of CKD. Company Logo

  30. HCV vs. CKD -- associated Company Logo

  31. HCV vs. CKD -- associated Company Logo

  32. HCV vs. CKD -- associated Company Logo

  33. HCV vs. CKD -- associated • Study Design: Cross-sectional study. • Setting & Participants: A large-scale community study with 54,966 adults in a Taiwanese county endemic for HBV and HCV infection. • Conclusions: HCV infection, but not HBV infection, was associated significantly with prevalence and disease severity of CKD in this HBV and HCV endemic area Company Logo

  34. HCV vs. CKD -- associated Company Logo

  35. HCV vs. CKD -- not associated • METHODS: We conducted a cohort study of 167,569 patients included in a national health care claims database from January 1, 2003–December 31, 2006, with a mean follow-up of 25.3 months. We used multivariable logistic regression analyses to measure the independent effect of HCV status on the baseline prevalence of and progression to CKD • CONCLUSIONS: We found no association between HCV and risk of development of CKD. Company Logo

  36. HCV vs. CKD – not associated Company Logo

  37. HCV vs. CKD – not associated Company Logo

  38. Mechanism and Pathogenesis of HCV induced renal injury -1 Hepat Mon. 2010; 10(4): 258-269 Company Logo

  39. Mechanism and Pathogenesis of HCV induced renal injury -2 Company Logo

  40. Mechanism and Pathogenesis of HCV induced renal injury -4 Hepat Mon. 2010; 10(4): 258-269 Company Logo

  41. Mechanism and Pathogenesis of HCV induced renal injury -5 • Mixed cryoglobulinemia induced GN • The most documented extrahepatic manifestation of hepatitis C virus (HCV) infection is mixed cryoglobulinemia (MC). • MC is characterised by the presence of temperature-sensitive protein complexes • precipitates when the serum is incubated at a temperature lower than 37C. • in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgMk) against polyclonal IgG Lupus (2000) 9, 83±91 Company Logo

  42. Mechanism and Pathogenesis of HCV induced renal injury -6 Lupus (2000) 9, 83±91 Company Logo

  43. Mechanism and Pathogenesis of HCV induced renal injury -7 Nephrol Dial Transplant (2007) 22: 1840–1848 Company Logo

  44. Mechanism and Pathogenesis of HCV induced renal injury -8 (B) Non-cryoglobulinaemic membranoproliferative glomerulonephritis (C) Membranous nephropathy (D) Focal and segmental sclerosis (E) Amyloidosis (F) Fibrillary glomerulonephritis. (G) Post-transplant thrombotic microangiopathy (H) Transplant glomerulopathy Company Logo

  45. Treatment of HCV in CKD Patients

  46. Antiviral therapy -- Interferon • Interferons are an important part of the innate antiviral immune response. • They induce interferon-stimulated genes (ISGs) that help establish an antiviral state within cells • Act by binding to cell surface receptors, activating a response cascade that culminates in the expression of multiple ISGs, some of which block viral protein synthesis. In addition, it may lead to a decrease in viral RNA stability. Company Logo

  47. Antiviral therapy -- Interferon • Alpha interferons also interact with the adaptive immune system. • It promote the proliferation of memory T-cells, prevent T-cell apoptosis, stimulate natural killer cell activation, and stimulate dendritic cell maturation. • It also upregulate the production of major histocompatibility complex class-I and class-II peptides and may promote a T-helper-1 phenotype over a T-helper-2 phenotype. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 2005; 436:967. Company Logo

  48. Antiviral therapy -- PEG-Interferon • The attachment of polyethylene glycol to a protein (pegylation) reduces its rate of absorption following subcutaneous injection, reduces renal and cellular clearance, and decreases the immunogenicity of the protein. • All of these effects tend to enhance the half-life of the pegylated versus the native protein. • On the other hand, pegylation may interfere with the ability of a protein to bind to its receptor, thereby decreasing its biologic effect. Thus, the true biologic effect of the pegylated protein is determined by the balance of these competing properties • Two formulations of peginterferon alfa have been developed: peginterferon alfa-2a (Pegasys, Roche Pharmaceuticals), and peginterferon alfa-2b (Peg-Intron, Schering-Plough Corporation).  Immunogenicity of recombinant IL-2 modified by covalent attachment of polyethylene glycol. J Immunol 1990; 144:209 Company Logo

  49. Antiviral therapy -- Ribavirin • Ribavirin is a nucleoside analog which has a broad spectrum of antiviral activity • It inhibits the replication of RNAviruses in cell culture. Ribavirin appears to decrease hepatitis C virus infectivity in a dose-dependent manner • Several mechanisms may be involved: • Depletion of intracellular triphosphate pools through direct inhibition of inosine monophosphate dehydrogenase • Inhibition of the 5'-cap structure of viral mRNA • Inhibition of the viral-dependent RNA polymerases • Altering the balance between proinflammatory (Th1-like) and antiinflammatory (Th2-like) cytokines • Inducing mutations into viral RNA • Potentiating interferon action  Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 2004; 432:922 Company Logo

  50. Treatment of HCV -1 HEPATOLOGY, Vol. 49, No. 4, 2009 Company Logo

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