Hepatitis C virus & chronic kidney diseases
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Hepatitis C virus & chronic kidney diseases

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  • Hepatitis C Virus Infections in Dialysis Centers in The Netherlands: a National Survey by Serological and Molecular Methods. Schneeberger PM et al. J ClinMicrobiol June 1998, p. 1711–1715.Abstract: A national survey of hepatitis C virus (HCV) infections among dialysis patients in The Netherlands was performed. The study involved 2,653 patients (2,108 hemodialysis patients and 545 chronic ambulatory peritoneal dialysis [CAPD] patients) from 39 of the 49 dialysis centers in the country. Patient sera were analyzed by both serological and molecular methods. Screening by a third-generation enzyme immunoassay (EIA) yielded 79 reactive sera. The presence of anti-HCV antibodies was confirmed in 70 patients by a line immunoassay. All seropositive samples were tested by reverse transcriptase PCR, and 57 samples were found to contain HCV RNA. Of the nine EIA-positive and line immunoassay-negative or indeterminate samples, four were HCV RNA positive. All seronegative samples were screened for the presence of HCV RNA in pools of five sera. Of 2,576 antibody-negative samples, 6 contained HCV RNA. All antibody-positive and RNA-positive samples were also tested by a second serological assay. The prevalence of HCV infections among Dutch dialysis patients as determined by serology or the presence of HCV RNA was 3% (80 of 2,653), i.e., 3.5% (73 of 2,108) in patients treated on hemodialysis and 1.3% (7 of 545) in patients on CAPD. Of these 80 HCV-infected dialysis patients, 67 (84%) were HCV RNA positive. Serological screening alone would have diagnosed only 70 infected patients. Therefore, antibody screening combined with detection of HCV RNA should be considered as the “gold standard” for diagnosing HCV infection in dialysis patients. The prevalence of HCV-infected patients inDutch dialysis centers ranged from 0 to 8%, suggesting the existence of local risk factors for acquiring HCV infection. Genotyping analysis by reverse hybridization line probe assay revealed the presence of genotypes 1a (23%), 1b (46%), 2 (3%), 2a (13%), 2b (1%), 3a (7%), and 4a (4%). In four (6%) samples multiple genotypes were detected. The genotype distribution of HCV isolates among Dutch dialysis patients was similar to the distribution among nondialysis patients from the Benelux, except for subtype 1a, which was significantly moreprevalent among dialysis patients. In only one center, a high prevalence of an uncommon genotype was suggestive of infection from a common source.
  • Liver biopsy provides key information on the extent of HCVassociated hepatic disease, but requires caution in CKD because of the potential low risk of bleeding complications, especially in patients with chronic kidney diseases. Transjugular biopsy seems safer.Percutaneous liver biopsy is safe in chronic hepatitis C patients with end-stage renal disease.Pawa S et al. ClinGastroenterolHepatol2007 Nov;5(11):1316-20.AbstractBackground & Aims: Liver biopsy is useful for staging fibrosis in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) to determine renal transplant eligibility and to make CHC treatment decisions. There is concern about an increased risk associated with percutaneous liver biopsy (PCNB) in ESRD patients. We compared the safety of PCNB in CHC patients with and without ESRD. Methods: We reviewed PCNBs performed between 1996 and 2004 for technique, histology, and complications in 78 ESRD patients with CHC and in 241 control patients with CHC and no renal failure, randomly matched for age, sex, and race. Platelet counts, prothrombin, and partial thromboplastin times, but not bleeding times, were checked before biopsy. Deamino-8-D-arginine vasopressin was not given before the biopsy. Results: The mean age of the patients was 50 years; 72% were male, 97% were African American, and 3% were Caucasian. The control group had a significantly higher proportion of patients with advanced fibrosis (P < .04). Only 1 patient with ESRD (1.3%) developed a moderate complication. Five controls (2.1%) developed complications, 3 of which were severe. Conclusions: Severe complications after PCNB are uncommon, and patients with ESRD and CHC are at no increased risk. Testing for bleeding time and the routine use of deamino-8-D-arginine vasopressin are not necessary before PCNB in patients with ESRD.
  • Fibrotest:Algorithm combining the results of serum tests of 2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT, & ALT to assess the level of fibrosis and necroinflammatory activity. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T: MULTIVIRC Group: Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: A prospective study. Lancet 357: 1069–1075, 2001.SummaryBackground: Liver biopsy is thought mandatory for management of patients with hepatitis C virus (HCV) infection, especially for staging fibrosis. We aimed, in our prospective study, to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinically significant fibrosis (including early stages). Methods: We assessed liver-biopsy patients with detectable HCV by PCR, for eligibility, and took a blood sample on the day of the procedure. The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients. We devised a fibrosis index that included the most informative markers (combined with age and sex) for the first-year group. 11 serum markers were assessed as well as fibrosis stage: FO=no fibrosis and F1=portal fibrosis; and for clinically significant fibrosis, F2=few septa, F3=many septa, and F4=cirrhosis. Statistical analysis was by logistic regression, neural connection, and receiver-operating characteristic (ROC) curves. Findings: First-year and second-year patient-group characteristics and biochemical markers did not differ. The overall frequency of clinically significant fibrosis was 40% (138 patients). The most informative markers were: α2 macroglobulin, α2 globulin (or haptoglobin), γ globulin, apolipoprotein A1, γ glutamyltranspeptidase, and total bilirubin. The areas (SD) under the ROC curves for the first-year (0·836 [0·430]) and second-year groups (0·870 [0·340]) did not differ (p=0·44). With the best index, a high negative predictive value (100% certainty of absence of F2, F3, or F4) was obtained for scores ranging from zero to 0·10 (12% [41] of all patients), and high positive predictive value (>90% certainty of presence of F2, F3, or F4) for scores ranging from 0·60 to 1·00 (34% of all patients). Interpretation: A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection.Diagnostic accuracy of the fibrotest in hemodialysis and renal transplant patients with chronic hepatitis C virus.Varaut A et al. Transplantation 2005 Dec 15;80(11):1550-5.AbstractBackground: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis & renal transplant patients infected by chronic HCV. Methods: In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied. Results: Forty-six percent of patients had fibrosis > or =F2. A positive predictive value of a score >0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of < 0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (< 0.6 and >0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients. Conclusion: The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.
  • Castera L et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343–350.Background & Aims:Transient elastography (FibroScan; Echosens, Paris, France) is a novel, noninvasive, and rapid bedside method to assess liver fibrosis by measuring liver stiffness. We prospectively assessed the performance of FibroScan in patients with chronic hepatitis C, in comparison with and combined with currently available biochemical markers (Fibrotest; Biopredictive; and the aspartatetransaminase to platelets ratio index [APRI]); a liver biopsy examination performed the same day served as the reference. Methods:We studied 183 consecutive patients with chronic hepatitis C (METAVIR fibrosis stage F1, n = 47; F2, n = 53; F3, n = 37; F4, n = 46). Results:FibroScan values ranged from 2.4 to 75.4 kilopascals (median, 7.4 kilopascals). Cut-off values were 7.1 kPa for F ≥ 2, 9.5 kPa for F ≥ 3, and 12.5 kPa for F = 4. The areas under the receiver operating characteristic (ROC) curve of FibroScan, FibroTest, and APRI values were of the same order (.83, .85, and .78, respectively, for F ≥ 2; .90, .90, and .84, respectively, for F ≥ 3; and .95, .87, and .83, respectively, for F = 4). The best performance was obtained by combining the FibroScan and FibroTest, with areas under the ROC curve of .88 for F ≥ 2, .95 for F ≥ 3, and .95 for F = 4. When the FibroScan and FibroTest results agreed, liver biopsy examination confirmed them in 84% of cases for F ≥ 2, in 95% for F ≥ 3, and in 94% for F = 4. Conclusions:FibroScan is a simple and effective method for assessing liver fibrosis, with similar performance to FibroTest and APRI. The combined use of FibroScan and FibroTest to evaluate liver fibrosis could avoid a biopsy procedure in most patients with chronic hepatitis C.
  • The most common HCV-related nephropathy is MPGN, usually in the context of cryoglobulinemia.
  • Cryoglobulins are single or mixed immunoglobulins that reversibly precipitate at low temperatures.Before the discovery of HCV and the establishment of serological tests for the detection of specific circulating anti-HCV antibodies, patients without identifiable underlying disease were considered to have “essential” mixed cryoglobulinaemia. In hindsight, it is now clearthat most of these patients were chronically infected with HCV.The incidence of HCV infection in “essential” mixed cryoglobulinaemia varies geographically, generally falling in the range of 40–100% (90% in the Mediterranean basin).
  • KayaliZeid et al. Hepatitis C, Cryoglobulinemia, and Cirrhosis: A Meta-analysis. Hepatology 2002;36:978-985.Approximately 40% of patients with chronic hepatitis C virus (HCV) infection develop detectable serum cryoglobulins or cryoprecipitates (CP), although most do not show clinical or physical signs of syndromiccryoglobulinemia. Although association of HCV with theextrahepatic complications of cryoglobulinemia is widely recognized, the relationship of cryoglobulinemia with liver disease is unclear. We wished to study the relationship between CP and cirrhosis and to determine whether the development of CP is a true covariate forprogressive liver disease or a confounding variable that impacts cirrhosis because of patient age, duration of disease, or differences in gender. We undertook ameta-analysis of 19 studies published between 1994 and 2001. The incidence of cirrhosis was compared in patients with and without CP after logistic regression adjustments for accepted risk factors for progressive liver disease, including age, gender, and estimated duration of disease (EDD). A total of 2,323 patients with chronic hepatitis C were identified, with 1,022 (44%) having detectable CP. Cirrhosis was present in 40% of patients with CP but only 17% of patients without CP (total x2 141.69, P < .001). After adjusting for age, gender, and estimated duration of disease by logistic regression, the combined odds ratio for incidence of cirrhosis in patients CP positive versus CP negative was 4.87, (95% CI: 3.32, 7.15), indicating a highly significant association between cirrhosis and cryoglobulinemia. In conclusion, cryoglobulins may be a useful prognostic indicator for increased risk of cirrhosis with chronic hepatitis C.
  • Any organ may be affectedPalpable purpura is evident in more than 90% of mixed cryoglobulinaemia patients, and is usually the first sign of cryoglobulinaemia, raising an immediate suspicion of cryoglobulinaemicvasculitis and foreshadowing systemic complications. Triad: purpura, asthenia, arthralgia & oserved in 30% of cases
  • PatientsThe study cohort was selected from the larger population of patients who underwent at least 1 serum creatinine measurementwithin the VA between October 1, 2000, and September 30, 2001 (n=2 352 584). The date of the first serum creatinine measurement during this period served as the point of cohortentry. We excluded patients who were already undergoing dialysis or who had undergone kidney transplantation (n=11 125). Among the remaining patients, 474 369 were tested for HCV within 1 year before or 1 year after cohort entry and comprised the analytic cohort for this study.Veterans AffairsIn 1988, the VA launched a major initiative to test all veterans at risk for HCV; the VA has the largest program for screening HCV in the United States. Screening is recommended among the following: Vietnam-era veterans, recipients of blood transfusions prior to 1992, individuals with a history of intravenous drug use, unequivocal blood exposure of skin or mucous membranes, multiple sexual partners (10 lifetime), hemodialysis, tattoo or repeated body piercings, intranasal cocaine use, unexplained liver disease, abnormal alanineaminotransferase levels, or heavy alcohol use, and individuals who express a desire to be screened.This is the first study, to our knowledge, that demonstrates an association between HCV and ESRD in a national cohort of health care users.Limitations: 1- This study was restricted to veteran health care users who had received HCV testing; therefore, results may not be generalizable to nonveteran populations. 2- Also did not have information on proteinuria or albuminuria in our cohort, as it was infrequently ordered by physicians; therefore, we could not determine whether proteinuria was a risk factor for ESRD risk among patients with HCV.3- Our follow-up time was short given the natural history of most types of kidney disease: it is possible that the strength and magnitude of the associations described herein might differ during a longer follow-up period.Conclusion:In this large national cohort of adult veterans, patients younger than 70 years with HCV seropositivity were at increased risk for developing ESRD treated with dialysis or transplantation.
  • It has been estimated that, among patients on hemodialysis, the prevalence of HCV infection varies greatly, from less than 5% to nearly 60% according to different areas of the world. The prevalence is consistently associated with patient age and the number of transfused blood products. The prevalence of HCV infection has declined in many dialysis centers, and yet it remains unacceptably high, ranging from 8% to 10% even in the most industrialized countries.Spontaneous disappearance of HCV RNA has been reported in 1% of untreated dialysis patients.
  • Increasing years on dialysis has been the risk factor most consistently reported as being independently associated with higher rates of HCV infection. As the number of years patients were on dialysis increased, their prevalence of HCV infection increased from an averageof 12% to an average of 37%. This relationship was found even for patients with no history of blood transfusion or injecting drug use, suggesting that HCV might be transmitted between patients in the hemodialysis setting.Kellerman S et al. Hepatology 1999;29:291-293.
  • Fabrizi F et al. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat2007 Oct;14(10):697-703.Abstract:The impact of hepatitis C virus (HCV) infection on mortality of patients receiving regular dialysis remains unclear. The assessment of the natural history of HCV in dialysis population is difficult because of the low progression of HCV-related liver disease over time and the reduced life expectancy in patients with end-stage renal disease. The aim of the study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on the survival of patients undergoing maintenance dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. We identified seven studies involving 11 589 unique patients on maintenance dialysis; two (29%) were case-control studies. Pooling of study results demonstrated that presence of anti-HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (aRR) (all-cause mortality) was 1.34 with a 95% confidence interval (CI) of 1.13-1.59. Heterogeneity statistics, R(i) = 0.48 (P-value by Q-test = 0.13). In a sensitivity analysis including only (n = 5) cohort studies, the pooled aRR was 1.38 (95% CI, 1.20-1.59); heterogeneity statistics R(i) = 0.46. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti-HCV-positive than -negative dialysis patients. Our meta-analysis indicates that anti-HCV-positive patients on dialysis have an increased risk of mortality compared with HCV-negative patients. The excess risk of death in HCV-positive patients may be at least partially attributed to chronic liver disease with its attendant complications.
  • Dolores Arenas M et al. A multicentric survey of the practice of hand hygiene in haemodialysis units: factors affecting compliance. Nephrol Dial Transplant (2005) 20: 1164–1171. SpainBackground: This study intended to investigate the degree of compliance with hand hygiene and use of gloves by health workers in haemodialysis (HD) units, and the factors that influenced adherence to hand hygiene protocols.Methods: During the month of November 2003, one person observed the health care staff in each of nine different dialysis units, during 495 randomly distributed 30 min observation periods that covered all steps of a haemodialysis session (connection, dialysis anddisconnection). The observers noted the number of potential opportunities to implement standard precautions and the number of occasions on which the precautions were actually taken. Adherence to standard precautions was evaluated, analysing the influenceof the following variables: the patient-to-nurse ratio, the number of HD shifts scheduled per day, acute HD units vs chronic, whether or not infectious patients were isolated and in-house vs contract cleaning personnel.Results: There were a total of 977 opportunities to wear gloves for, and to wash the hands following, a patient-oriented activity, and 1902 opportunities to wash hands before such an activity. Gloves were actually used on 92.9% of these occasions. Hands werewashed only 35.6% of the time after patient contact, and only 13.8% of the time before patient contact. Poor adherence to hand washing was associated with the number of shifts per HD unit per day and with higher patient-to-nurse ratios. In the acute HD units, there was greater adherence to standard precautions than in the chronic units, although there too it was substandard. The personnel’s knowledge of patients’ infectious status did not modify their adherence to hand hygiene practices. A higher patient-to-nurse ratio independently influenced hand washing both before and after patient contact.Conclusions: The overall adherence of health care workers to recommended hand washing practices is low. Whether or not programmes promoting higher hand hygiene standards and the potential use of alcohol-based hand cleansers will improve hand hygiene practices in HD units requires further investigation.
  • Cryoglobulins are single or mixed immunoglobulins that reversibly precipitate at low temperatures.Before the discovery of HCV and the establishment of serological tests for the detection of specific circulating anti-HCV antibodies, patients without identifiable underlying disease were considered to have “essential” mixed cryoglobulinaemia. In hindsight, it is now clearthat most of these patients were chronically infected with HCV.The incidence of HCV infection in “essential” mixed cryoglobulinaemia varies geographically, generally falling in the range of 40–100% (90% in the Mediterranean basin).
  • HCV core protein is linked to IgG molecules with specific anticore reactivity, which in turn are bound to IgM molecules with rheumatoid factor activity. Multimolecular complexes are good acceptors of C1q protein, and this results in specific binding to endothelial cells via the C1q receptor (C1qR). In boxes, the relative proportions of IgG, IgM, and complement proteins in relation to cryoprecipitate and supernatant phases are depicted.
  • Dolores Arenas M et al. A multicentric survey of the practice of hand hygiene in haemodialysis units: factors affecting compliance. Nephrol Dial Transplant (2005) 20: 1164–1171. SpainBackground: This study intended to investigate the degree of compliance with hand hygiene and use of gloves by health workers in haemodialysis (HD) units, and the factors that influenced adherence to hand hygiene protocols.Methods: During the month of November 2003, one person observed the health care staff in each of nine different dialysis units, during 495 randomly distributed 30 min observation periods that covered all steps of a haemodialysis session (connection, dialysis anddisconnection). The observers noted the number of potential opportunities to implement standard precautions and the number of occasions on which the precautions were actually taken. Adherence to standard precautions was evaluated, analysing the influenceof the following variables: the patient-to-nurse ratio, the number of HD shifts scheduled per day, acute HD units vs chronic, whether or not infectious patients were isolated and in-house vs contract cleaning personnel.Results: There were a total of 977 opportunities to wear gloves for, and to wash the hands following, a patient-oriented activity, and 1902 opportunities to wash hands before such an activity. Gloves were actually used on 92.9% of these occasions. Hands werewashed only 35.6% of the time after patient contact, and only 13.8% of the time before patient contact. Poor adherence to hand washing was associated with the number of shifts per HD unit per day and with higher patient-to-nurse ratios. In the acute HD units, there was greater adherence to standard precautions than in the chronic units, although there too it was substandard. The personnel’s knowledge of patients’ infectious status did not modify their adherence to hand hygiene practices. A higher patient-to-nurse ratio independently influenced hand washing both before and after patient contact.Conclusions: The overall adherence of health care workers to recommended hand washing practices is low. Whether or not programmes promoting higher hand hygiene standards and the potential use of alcohol-based hand cleansers will improve hand hygiene practices in HD units requires further investigation.
  • Dolores Arenas M et al. A multicentric survey of the practice of hand hygiene in haemodialysis units: factors affecting compliance. Nephrol Dial Transplant (2005) 20: 1164–1171. SpainBackground: This study intended to investigate the degree of compliance with hand hygiene and use of gloves by health workers in haemodialysis (HD) units, and the factors that influenced adherence to hand hygiene protocols.Methods: During the month of November 2003, one person observed the health care staff in each of nine different dialysis units, during 495 randomly distributed 30 min observation periods that covered all steps of a haemodialysis session (connection, dialysis anddisconnection). The observers noted the number of potential opportunities to implement standard precautions and the number of occasions on which the precautions were actually taken. Adherence to standard precautions was evaluated, analysing the influenceof the following variables: the patient-to-nurse ratio, the number of HD shifts scheduled per day, acute HD units vs chronic, whether or not infectious patients were isolated and in-house vs contract cleaning personnel.Results: There were a total of 977 opportunities to wear gloves for, and to wash the hands following, a patient-oriented activity, and 1902 opportunities to wash hands before such an activity. Gloves were actually used on 92.9% of these occasions. Hands werewashed only 35.6% of the time after patient contact, and only 13.8% of the time before patient contact. Poor adherence to hand washing was associated with the number of shifts per HD unit per day and with higher patient-to-nurse ratios. In the acute HD units, there was greater adherence to standard precautions than in the chronic units, although there too it was substandard. The personnel’s knowledge of patients’ infectious status did not modify their adherence to hand hygiene practices. A higher patient-to-nurse ratio independently influenced hand washing both before and after patient contact.Conclusions: The overall adherence of health care workers to recommended hand washing practices is low. Whether or not programmes promoting higher hand hygiene standards and the potential use of alcohol-based hand cleansers will improve hand hygiene practices in HD units requires further investigation.

Hepatitis C virus & chronic kidney diseases Hepatitis C virus & chronic kidney diseases Presentation Transcript

  • 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 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.
  • 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 & 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%
  • 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
  • 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 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
  • 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.
  • 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.
  • 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 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.
  • 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
  • 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.
  • 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
  • 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) 2000 Martin P et al. J Hepatol 2008;49:613–624.
  • 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.
  • HCV prevalence & time on dialysis Fissell RB et al. Kidney Int 2004;65:2335–2342.
  • 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.
  • 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
  • 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 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
  • 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
  • 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.
  • KDIGO Kidney 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 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
  • 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 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.
  • 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 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.
  • HCV & death risk in hemodialysis patients Kalantar-Zadeh K et al. J Am Soc Nephrol 2007;18:584–1593.