Hepatitis B and C serologic profiles of Canadian organ donors and recipients: retrospective 10-year review at a single center.

BACKGROUND: Hepatitis C virus (HBV) and hepatitis C virus (HCV) are important causes of hepatitis and can be transmitted from organ donor to recipient. This study aimed to determine HBV and HCV serologic profiles of a population of Canadian solid organ transplant (SOT) donors and recipients, including prevalence of recipient HBV immunity. METHODS: Data on age, gender, organ transplanted, and pre-transplant HBV and HCV serology for SOT donors and recipients at a Canadian hospital from 2001 to 2011 were obtained from a transplant database. RESULTS: There were 2455 recipients (2205 adults, 250 children), and 1559 donors. Over 50% of adult and 44% of pediatric recipients were HBV non-immune pre-transplant. Pediatric recipients were more likely to have HBV vaccine immunity than were adult recipients (48.8% vs. 28.9%, P < 0.001). Prevalence of HBV vaccine immunity was highest in renal recipients (48.3% in adult, 63.2% in pediatric recipients). Recipient HBV vaccine immunity increased from 5.8% in 2001 to 44.5% in 2011 (P < 0.001). Of 134 adult recipients with prior HBV infection, 59 (44%) were co-infected with HCV. Only 0.6% of adult non-liver recipients had acute or chronic HBV infection and 3.2% were anti-HCV positive. Only 2 donors had acute or chronic HBV infection, 29 had prior HBV infection, 9 were isolated hepatitis B core antibody positive, and 15 were anti-HCV positive. CONCLUSIONS: The prevalence of HBV vaccine immunity in SOT candidates is low, but increased from 2001 to 2011. Opportunities for quality improvement in pre-transplant HBV immunization exist. HCV co-infection is common in recipients with prior HBV infection. Prevalence of HCV infection in non-liver transplant recipients is low.

Multicenter evaluation of a commercial cytomegalovirus quantitative standard: effects of commutability on interlaboratory concordance.

Commutability of quantitative reference materials has proven important for reliable and accurate results in clinical chemistry. As international reference standards and commercially produced calibration material have become available to address the variability of viral load assays, the degree to which such materials are commutable and the effect of commutability on assay concordance have been questioned. To investigate this, 60 archived clinical plasma samples, which previously tested positive for cytomegalovirus (CMV), were retested by five different laboratories, each using a different quantitative CMV PCR assay. Results from each laboratory were calibrated both with lab-specific quantitative CMV standards ("lab standards") and with common, commercially available standards ("CMV panel"). Pairwise analyses among laboratories were performed using mean results from each clinical sample, calibrated first with lab standards and then with the CMV panel. Commutability of the CMV panel was determined based on difference plots for each laboratory pair showing plotted values of standards that were within the 95% prediction intervals for the clinical specimens. Commutability was demonstrated for 6 of 10 laboratory pairs using the CMV panel. In half of these pairs, use of the CMV panel improved quantitative agreement compared to use of lab standards. Two of four laboratory pairs for which the CMV panel was noncommutable showed reduced quantitative agreement when that panel was used as a common calibrator. Commutability of calibration material varies across different quantitative PCR methods. Use of a common, commutable quantitative standard can improve agreement across different assays; use of a noncommutable calibrator can reduce agreement among laboratories.

Interlaboratory comparison of cytomegalovirus viral load assays.

To assess interlaboratory variability in qualitative and quantitative cytomegalovirus (CMV) viral load (VL) testing, we distributed a panel of samples to 33 laboratories in the USA, Canada and Europe who performed testing using commercial reagents (n = 17) or laboratory-developed assays (n = 18). The panel included two negatives, seven samples constructed from purified CMV nucleocapsids in plasma (2.0-6.0 log(10) copies/mL) and three clinical plasma samples. Interlaboratory variation was observed in both actual (range, 2.0-4.0 log(10) copies/mL) and self-reported lower limits of detection (range, 1.0-4.0 log(10) copies/mL). Variation observed in reported results for individual samples ranged from 2.0 log(10) (minimum) to 4.3 log(10) (maximum)(.) Variation was greatest at low VLs. Assuming +/- 0.5 log(10) relative to the expected result represents an acceptable result, 57.6% of results fell within this range. Use of commercially available reagents and procedures was associated with less variability compared with laboratory-developed assays. Interlaboratory variability on replicate samples was significantly greater than intralaboratory variability (p < 0.0001). The significant interlaboratory variability in CMV VL observed may be impacting patient care and limiting interinstitutional comparisons. The creation of an international reference standard for CMV VL assay calibration would be an important step in quality improvement of this laboratory tool.

Interlaboratory comparison of epstein-barr virus viral load assays.

To assess interlaboratory variability in qualitative and quantitative Epstein-Barr virus (EBV) viral load (VL) testing, we distributed a panel of samples to 28 laboratories in the USA, Canada and Europe who performed testing using commercially available reagents (n = 12) or laboratory-developed assays (n = 18). The panel included two negatives, seven constructed samples using Namalwa and Molt-3 cell lines diluted in plasma (1.30-5.30 log(10) copies/mL) and three clinical plasma samples. Significant interlaboratory variation was observed for both actual (range 1.30-4.30 log(10) copies/mL) and self-reported (range, 1.70-3.30 log(10) copies/mL) lower limits of detection. The variation observed in reported results on individual samples ranged from 2.28 log(10) (minimum) to 4.14 log(10) (maximum). Variation was independent of dynamic range and use of commercial versus laboratory-developed assays. Overall, only 47.0% of all results fell within acceptable standards of variation: defined as the expected result +/- 0.50 log(10). Interlaboratory variability on replicate samples was significantly greater than intralaboratory variability (p < 0.0001). Kinetics of change in VL appears more relevant than absolute values and clinicians should understand the uncertainty associated with absolute VL values at their institutions. The creation of an international reference standard for EBV VL assay calibration would be an initial important step in quality improvement of this laboratory tool.

Trends in testing behaviours for hepatitis C virus infection and associated determinants: results from population-based laboratory surveillance in Alberta, Canada (1998-2001).

Little is currently known about hepatitis C virus (HCV) test seeking behaviours at the population level. Given the centralized nature of testing for HCV infection in the province of Alberta, Canada, we had an opportunity to examine HCV testing behaviour at the population level on all newly diagnosed HCV-positive cases using laboratory data to validate the time and number of prior tests for each case. Record linkage identified 3323, 2937, 2660 and 2703 newly diagnosed cases of HCV infections in Alberta during 1998, 1999, 2000 and 2001, respectively, corresponding to age-adjusted rates of 149.8, 129, 114.3 and 113.7 per 100,000 population during these years, respectively. Results from secondary analyses of laboratory data suggest that the majority of HCV cases (95.3%) who were newly diagnosed between 1998 and 2001 were first-time testers for HCV infection. Among repeat testers, analysis of a negative test result within 1 year prior to a first of a positive test report suggests that 211 (38.4%) may be seroconvertors. These findings suggest that 339 or 61.7% of repeat testers may not have discovered their serostatus within 1 year of infection. Among this group, HCV testing was sought infrequently, with a median interval of 2.3 years between the last negative and first positive test. This finding is of concern given the risks for HCV transmission, particularly if risk-taking behaviours are not reduced because of unknown serostatus. These findings also reinforce the need to make the most of each test-seeking event with proper counselling and other appropriate support services.

Prevalence and estimated incidence of blood-borne viral pathogen infection in organ and tissue donors from northern Alberta.

To determine the potential safety benefit of introducing nucleic acid testing (NAT) in tissue and organ donors, the risk of virus transmission was examined in a Canadian population. Anonymous data on Northern Alberta tissue and organ donors from 1998 to 2004 were used to determine the seroprevalence and estimate the seroincidence and residual risk of HIV, HBV, HCV and HTLV infection. Of the 3372 donors identified, 71.1% were surgical bone, 13.2% were living organ and 15.6% were deceased organ/tissue donors. Seroprevalence was: HIV 0.00%, HBV 0.09%, HCV 0.48% and HTLV 0.03%. Incidence (/100,000 p-yrs) and residual risks (/100,000 donors) could only be estimated for HBV (24.2 and 3.9) and HCV (11.2 and 2.2). Risk estimates were higher for deceased donors than surgical bone donors. HCV had the highest prevalence and HBV had the highest estimated incidence. HIV and HTLV risks were extremely low precluding accurate quantification. In this region of low overall viral prevalence, HCV NAT would be most effective in deceased organ donors. In surgical bone donors the cost of implementing NAT is high without significant added safety benefit.

A review of general hepatitis C virus lookbacks in Canada.

BACKGROUND AND OBJECTIVES: This article reviews the Canadian experience with general hepatitis C virus (HCV) lookback programmes. MATERIALS AND METHODS: Comprehensive literature searches were conducted in PubMed, Medline, HealthSTAR and EMBASE. In addition, bibliographic searches were performed on all retrieved articles, and provinces were contacted to determine whether they had performed general HCV lookbacks. RESULTS: Of the seven Canadian general HCV lookbacks identified, two focused specifically on the paediatric population. The proportion of transfused patients presumed to be alive varied from 48.9 to 97.5%. Between 55.3 and 99.1% of letters were successfully delivered. The proportion of patients tested for HCV and subsequently found to be HCV positive varied considerably (66.2-80.4% and 0.9-5.0%, respectively). Newly diagnosed patients represented 42-58% of cases identified. CONCLUSIONS: The Canadian general HCV lookback experience successfully identified previously undiagnosed HCV-positive patients, but the resources required to notify patients are high and the yield is relatively low. The effectiveness may be greatest in the paediatric population.

Diagnosis and management of posttransplant lymphoproliferative disorder in solid-organ transplant recipients.

The Epstein-Barr virus (EBV) has a pivotal pathophysiologic role in the development of most lymphoproliferative disorders that occur after solid-organ transplantation. The term "EBV-associated posttransplant lymphoproliferative disorder" (PTLD) includes all clinical syndromes of EBV-associated lymphoproliferation, ranging from uncomplicated posttransplant infectious mononucleosis to true malignancies that contain clonal chromosomal abnormalities. PTLDs are historically associated with a high mortality rate in patients who have a monoclonal form of the disorder. Recently described approaches to pathology, diagnosis, treatment, and preventive strategies of PTLD, however, have the potential to improve outcome.

Recurrent Epstein-Barr virus associated disease in a cardiac transplant patient: evolution from plasmacytic hyperplasia to diffuse large cell lymphoma.

An Epstein-Barr virus (EBV)-seronegative 31-year-old male underwent cardiac transplantation in 1991 for congenital cardiomyopathy. He presented with a protracted course of waxing and waning lymphadenopathy beginning four years after transplantation with eventual progression to a fulminant EBV-positive large cell lymphoma eight years after transplantation. Risk factors for the development of post-transplant lymphoproliferative disease in this patient, the importance of a standardized approach to pathology in assessing therapeutic options, and the management strategies used are discussed.

Ogilvie's syndrome associated with acute cytomegaloviral infection after liver transplantation.

Ogilvie's syndrome, or acute colonic pseudo-obstruction, is a rare complication following liver transplantation. We describe two cases in which the onset of Ogilvie's syndrome is strongly temporally associated with acute cytomegaloviral (CMV) infection in immunosuppressed liver transplant recipients. The pseudo-obstruction resolved rapidly in both cases following treatment with intravenous ganciclovir. Acute CMV infection therefore appeared to be causally linked to pathogenesis of Ogilvie's syndrome in these two cases. This association has not been described previously to our knowledge, and should be considered in any transplant patient presenting with Ogilvie's syndrome.

Hepatitis C prevalence and risk factors in the northern Alberta dialysis population.

Hepatitis C virus (HCV) is an emerging global public health issue with particular relevance in multiply transfused renal dialysis patients. This cross-sectional study evaluated the prevalence and risk factors for HCV infection among renal dialysis patients in northern Alberta, Canada. Ninety-two percent of eligible patients (n = 336) provided informed consent to participate. Participants were interviewed to gather risk factor information and, using multiple logistic regression analysis with exact inference, a predictive model for HCV infection in this population was developed. The prevalence of HCV infection in the population was 6.5%, and all positive patients had at least one identifiable risk factor. The multivariate analysis showed that the risk of HCV infection was greater for those in the 18-55 years age category (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.2-27.9), patients who had been on dialysis > 5 years (OR = 3.7, 95% CI 1.2-12.0), and patients who had > or = 2 high risk life-style behaviors (OR = 5.0, 95% CI 1.5-16.7). Transfusion prior to 1990 was marginally associated with HCV status (OR = 4.0, 95% CI 0.96-16.3). This study documented previously unreported life-style risk factors for HCV infection in patients with renal failure, confirmed the expected decline in transfusion-acquired HCV infection in this population, and provided evidence against nosocomial transmission of HCV.

Validation of self-reported transfusion histories in renal dialysis patients.

The purpose of this analysis was to assess the validity of self-reported transfusion histories in dialysis patients. Using data from a cross-sectional study of a dialysis population being investigated for hepatitis C virus (HCV) infection, the correspondence between self-reported transfusion history and transfusion records was explored. Demographic data and dialysis histories were examined in relation to the accuracy of self-reports. Overall, the questionnaire data and the blood bank records agreed for 89% of participants. The Kappa statistic was 0.72 (95% CI: 0.61, 0.83) indicating an acceptable level of agreement. The effect of non-differential exposure misclassification on the risk estimates for transfusion history as a determinant of HCV infection is demonstrated. Exploring the discrepancies between self-reports and documented transfusion histories underlines the need to communicate clearly medical interventions in chronically ill patients. Additionally, it suggests that studies into transfusion-acquired blood-borne pathogens should use all available information sources to establish exposure.

Transfusion- and community-acquired cytomegalovirus infection in children with malignant disease: a prospective study.

BACKGROUND: The use of cytomegalovirus (CMV)-"safe" blood has been recommended for CMV seronegative patients with newly diagnosed malignant disease for whom bone marrow transplantation is a future option. STUDY DESIGN AND METHODS: To evaluate this policy, 76 CMV-seronegative children with lymphoreticular malignancies or solid tumors were randomly assigned to receive either blood components that were not screened for CMV antibody or CMV-seronegative red cell (RBC) and platelet units. Subjects were followed for evidence of CMV infection by the use of enzyme-linked immunosorbent assays and virus isolation. Follow-up continued long after the blood transfusions to determine the risk of community-acquired CMV infection. RESULTS: No cases of transfusion-acquired CMV infection were documented. The prevalence of CMV IgG and IgM antibody in blood donors was 40.5 and 0.9 percent, respectively. Patients assigned to receive standard blood components and CMV-negative components were given a median (range) of 7 (1-30) and 9 (1-38) RBC units and 11 (0-123) and 14 (0-71) platelet units, respectively. The risk of transfusion-acquired CMV infection is estimated to be less than 1 in 698 donor exposures. Two patients developed asymptomatic community-acquired CMV infection, for an incidence of 1.7 percent per patient-year of follow-up. CONCLUSION: The risk of transfusion-acquired CMV infection in this population is low, largely because of the patients' low level of exposure to seropositive blood and the use of relatively white cell-reduced components for purposes other than CMV prevention. Such children at this center therefore continue to receive standard blood components. Strategies to prevent CMV seroconversion in these children should include parental education to minimize the risk of community-acquired infection.

Human immunodeficiency virus seroprevalence and risk behaviors in patients attending sexually transmitted disease clinics in Alberta.

OBJECTIVE: To investigate the dissemination of human immunodeficiency virus (HIV) and hepatitis C infection in association with sexually transmitted diseases (STDs), sexual practices, and injection drug use. All eligible men and women attending two STD clinics in Alberta, Canada, from May 1994 to May 1995 were studied. STUDY DESIGN: Anonymous, unlinked serosurveys were performed using leftover sera drawn for routine syphilis, hepatitis B, or HIV testing. Self-administered questionnaires collected a wide range of data: demographic, sexual behaviors, condom use, STD history, the exchange of drugs or money for sex, and drug and alcohol use. RESULTS: HIV seroprevalence in the overall sample group (n = 6,668) was 1.5%. Univariate analysis showed significant relationships for age between 30 years and 49 years, men having sex with men, injection drug use regardless of sexual orientation, history of STD, anal sex, and exchanging money or drugs for sex. At the multivariate level, only men having sex with men, injection drug use, and age more than 30 years remained predictive of HIV infection. The prevalence of hepatitis C was 3.4% with significant associations being injection drug use and exchanging money or drugs for sex. CONCLUSION: The behavioral associations between sex practices, injection drug use, and HIV and hepatitis C seroprevalence warrant ongoing investigation. Continuing prevention programs targeted at safer sex practices (particularly for men having sex with men) and the use of clean needles are needed.

Serologic responses to hepatitis C virus in solid organ transplant recipients.

BACKGROUND: Hepatitis C (HCV) infection is known to have been transmitted by both blood transfusion and donor organs. We sought to determine the historical incidence of donor- and transfusion-acquired HCV infection in kidney transplant (RTx) and heart transplant (HTx) recipients at our center and to study the kinetics of seroconversion to HCV. METHODS: A bank of sera collected from organ donors (388 RTx and 88 HTx) who received allografts between January 1984 and April 1992 was screened for anti-HCV using a third generation enzyme immunoassay. Recipient sera collected before transplant (preTx), at 1 year after transplant, and at last follow-up were tested. Fresh follow-up sera on all surviving anti-HCV-positive (+) RTx and HTx, all anti-HCV-negative (-) HTx, and a subset of 85 anti-HCV- RTx were assayed for HCV RNA using an reverse transcriptase-polymerase chain reaction assay. RESULTS: Twenty-four of 388 RTx (6.2%) and 2 of 88 HTx (2.3%) were anti-HCV+ preTx. Eight of 218 (3.7%) organ donors were anti-HCV+. Six of the seven (85.7%) anti-HCV+ donors with adequate recipient follow-up transmitted HCV infection to one or more recipients. Nineteen of 313 RTx (6.1%) and 8 of 72 HTx (11.1%) with follow-up > or =1 year seroconverted to anti-HCV. One of 85 (1.2%) anti-HCV- RTx and 3 of 44 (6.8%) anti-HCV-HTx were HCV RNA+ when tested at last follow-up. Five cases of de novo HCV infection occurred after the introduction of first generation anti-HCV screening of donors. Persistent viremia (HCV RNA+) at last follow-up was observed in 70.6% (12/17) RTx anti-HCV+ preTx. Fourteen of 15 (93.3%) RTx and 9 of 9 (100%) HTx with de novo HCV infection had persistent viremia. Seroconversion was more delayed in HTx than RTx (P=0.0572, log-rank Mantel-Cox statistic) although both groups demonstrated an impaired humoral response to HCV when compared with the immunocompetent host. CONCLUSIONS: Organ donor- and transfusion-acquired HCV infection was common in RTx and HTx transplanted before the introduction of second generation anti-HCV screening in 1992. Serologic responses to HCV are often delayed and sometimes absent in these patients. Assays for HCV RNA should be considered as a screening test for the detection of HCV infection in this population. Serologic responses to HCV were more impaired in HTx compared with RTx, which may reflect the more intensive immunosuppressive regimens given to HTx at our center.