Medicinal chemistry: The key to critical thinking in pharmacotherapy.

INTRODUCTION: Medicinal chemistry is a polarizing subject for pharmacy students where, if not embraced, future pharmacists may be limited in their role as drug experts. An understanding of medicinal chemistry and its structure-activity relationships creates a strong foundation upon which our knowledge of pharmacotherapy is built. PERSPECTIVE: As the field of pharmacy has shifted to an increasingly clinical role, with an emphasis on patient care as a member of the interprofessional team, pharmacy has also seen an increase in postgraduate training, specifically residencies and fellowships. Pharmacy students noting this trend may depreciate medicinal chemistry early in the curriculum and place more focus on therapeutics and clinical rotations. However, forgoing the fundamental understanding of medicinal chemistry may hinder pharmacy students' current breadth and understanding, and the ability to rationalize future developments in their practice. Medicinal chemistry empowers pharmacists with the ability to reason through medications' impact versus simply memorizing their actions. Pharmacists play a unique role as drug experts, with advanced problem-solving and critical thinking skills that set them apart from drug references and search engines. IMPLICATIONS: As the field moves towards pharmacists as a member of the clinical team, the faculty should integrate medicinal chemistry throughout the doctor of pharmacy curricula. Faculty without this ability for a curriculum change should consider integration in their content. The field of pharmacy must take care to not allow clinical knowledge to significantly overshadow the importance of medicinal chemistry or run the risk of saturating the field with underprepared pharmacists.

Cross sectional investigation of a COVID-19 outbreak at a London Army barracks: Neutralising antibodies and virus isolation.

BACKGROUND: Military personnel in enclosed societies are at increased risk of respiratory infections. We investigated an outbreak of Coronavirus Disease 2019 in a London Army barracks early in the pandemic. METHODS: Army personnel, their families and civilians had nasal and throat swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcriptase -polymerase chain reaction (RT-PCR), virus isolation and whole genome sequencing, along with blood samples for SARS-CoV-2 antibodies. All tests were repeated 36 days later. FINDINGS: During the first visit, 304 (254 Army personnel, 10 family members, 36 civilians, 4 not stated) participated and 24/304 (8%) were SARS-CoV-2 RT-PCR positive. Infectious virus was isolated from 7/24 (29%). Of the 285 who provided a blood sample, 7% (19/285) were antibody positive and 63% (12/19) had neutralising antibodies. Twenty-two (22/34, 64%) individuals with laboratory-confirmed infection were asymptomatic. Nine SARS-CoV-2 RT-PCR positive participants were also antibody positive but those who had neutralising antibodies did not have infectious virus. At the second visit, no new infections were detected, and 13% (25/193) were seropositive, including 52% (13/25) with neutralising antibodies. Risk factors for SARS-CoV-2 antibody positivity included contact with a confirmed case (RR 25.2; 95% CI 14-45), being female (RR 2.5; 95% CI 1.0-6.0) and two-person shared bathroom (RR 2.6; 95% CI 1.1-6.4). INTERPRETATION: We identified high rates of asymptomatic SARS-CoV-2 infection. Public Health control measures can mitigate spread but virus re-introduction from asymptomatic individuals remains a risk. Most seropositive individuals had neutralising antibodies and infectious virus was not recovered from anyone with neutralising antibodies. FUNDING: PHE.

Reuse of liver grafts following the brain death of the initial recipient.

AIM: To determine if there is a reasonable prospect of success of a re-use liver transplantation. METHODS: We systematically searched for reports of liver graft re-use using electronic searches of PubMed and Web of Knowledge. We performed hand searches of references lists of articles reporting re-use of grafts. RESULTS: A systematic review of the literature reveals 28 liver transplantations using previously transplanted grafts. First and second recipients ranged in age from 4 to 72 years and 29 to 62 years respectively. Liver disease in the first recipient was varied including 5 (18%) patients with fulminant liver failure who died subsequently of cerebral edema. The second transplantation was performed after a median interval of 5 d (one day-13 years). Viral hepatitis was present in 3 (11%) of the initial recipients and in 8 (29%) of final recipients. Hepatocellular carcinoma was present in 6 (21%) of the final recipients. Early survival after the final transplantation was 93%, whereas long-term survival was 78% with a mean follow-up of 23.3 (3-120) mo. CONCLUSION: Outcomes of transplantation using previously transplanted grafts in this select population are similar to those seen with conventional grafts.

Comparison of short- and long-term outcomes after early versus late liver retransplantation: a single-center experience.

BACKGROUND: As the survival of patients after liver transplantation (LT) improves, the requirement of liver retransplantation (reLT) for late graft failure has grown. Although some have reported that the short-term outcome of late reLT was comparable with that of early reLT, it remains unknown whether long-term survival of late reLT is inferior to that of early reLT patients. MATERIALS AND METHODS: We reviewed early (<6 mo after primary LT) and late (≥6 mo after primary LT) reLT cases performed between January 2000 and December 2010. RESULTS: Sixteen early and 32 late reLT cases were analyzed. There was no significant difference regarding the number of units of red blood cells transfused during the transplantation between the groups, whereas operative time was significantly longer in the late reLT cases. Graft loss within 3 mo after early and late reLT was 18.6% and 15.6%, respectively. Patient and graft survival rates after 1, 3, 5, and 10 y in the late reLT group were 80.6%, 73.3%, 73.3%, and 67.7% and 80.7%, 69.1%, 63.3%, and 54.3%, respectively, whereas those in the early reLT group were 75.0%, 75.0%, 64.3%, and 64.3% and 81.3%, 75.0%, 64.3%, and 32.1%, respectively. There was no significant difference in patient or graft survival rates between the groups (P = 0.91 and 0.91, respectively). CONCLUSIONS: Acceptable short- and long-term survival were provided in early and late reLT. The time between the primary LT and reLT does not seem to play significant role in the prognosis of reLT in the long term.

Inferior survival in liver transplant recipients with hepatocellular carcinoma receiving donation after cardiac death liver allografts.

The impact of ischemia/reperfusion injury in the setting of transplantation for hepatocellular carcinoma (HCC) has not been thoroughly investigated. The present study examined data from the Scientific Registry of Transplant Recipients for all recipients of deceased donor liver transplants performed between January 1, 1995 and October 31, 2011. In a multivariate Cox analysis, significant predictors of patient survival included the following: HCC diagnosis (P < 0.01), donation after cardiac death (DCD) allograft (P < 0.001), hepatitis C virus-positive status (P < 0.01), recipient age (P < 0.01), donor age (P < 0.001), Model for End-Stage Liver Disease score (P < 0.001), recipient race, and an alpha-fetoprotein level > 400 ng/mL at the time of transplantation. In order to test whether the decreased survival seen for HCC recipients of DCD grafts was more than would be expected because of the inferior nature of DCD grafts and the diagnosis of HCC, a DCD allograft/HCC diagnosis interaction term was created to look for potentiation of effect. In a multivariate analysis adjusted for all other covariates, this interaction term was statistically significant (P = 0.049) and confirmed that there was potentiation of inferior survival with the use of DCD allografts in recipients with HCC. In conclusion, patient survival and graft survival were inferior for HCC recipients of DCD allografts versus recipients of donation after brain death allografts. This potentiation of effect of inferior survival remained even after adjustments for the inherent inferiority observed in DCD allografts as well as other known risk factors. It is hypothesized that this difference could reflect an increased rate of recurrence of HCC.

Changing donor characteristics in liver transplantation over the last 10 years in Canada.

Liver donor characteristics have a significant impact on graft quality and, in turn, recipient outcomes. In this study, we examined deceased liver donor characteristics and donor risk index (DRI) trends in Canada over the past decade. Data were extracted from the Canadian Organ Replacement Register and Transplant Québec for the decade (2000-2010). Trends in the DRI and donor characteristics, including age, race, height, cause of death (COD), location, cold ischemia time (CIT), and type of donation, were examined. In all, 3746 transplants using deceased liver donors were analyzed. The age of donors, the proportion of black donors, the proportion of cerebrovascular accidents as the COD, and the proportion of donation after cardiac death (DCD) donors all increased over the aforementioned time period. The proportion of transplants classified geographically as local increased, and the CIT for donor livers decreased. Although many of the parameters adversely affecting the DRI increased over the study period, the DRI showed only a slightly significant trend of increasing. The increase in these parameters was counteracted by a decrease in modifiable risk factors such as the CIT and distance traveled. The 5-year recipient survival rate increased from 71.43% (1999-2001) to 75.50% (2005-2007); however, this trend was not significant. Although there was an increase in the use of older and DCD organs, recipient survival was not compromised. In conclusion, demographic trends for liver donors in Canada suggest an increase in the use of higher risk donors. However, the overall graft quality has been not compromised because of a decreasing trend for the CIT and an increase in local transplants. Better coordination and allocation practices in liver transplantation across Canada have minimized the risk of graft failure and resulted in good recipient outcomes.

Establishment of a stringent large animal model of insulin-dependent diabetes for islet autotransplantation: combination of pancreatectomy and streptozotocin.

OBJECTIVE: A stringent porcine islet autograft diabetes model was developed to enable the assessment of autoislet safety and efficacy in either portal vein or an extrahepatic site. METHODS: A 95% pancreatectomy was performed preserving the pancreaticoduodenal arcade; however, glycemic control was still maintained at 3.3 ± 0.3 days (mean ± SEM), shown by euglycemic fasting blood glucose levels of 4.9 ± 0.8 mmol/L (mean ± SEM, n = 3). To reduce surgical complications and eliminate remaining islets, pigs were dosed intravenously after a modified 90% pancreatectomy, with 150-mg/kg streptozotocin, producing a diabetic state (18.9 ± 1.8 mmol/L [mean ± SEM], n = 8; P < 0.001) within 2.0 ± 0.9 days (mean ± SEM). RESULTS: Animals presented with sustained hyperglycemia, failing a glucose challenge test 12 weeks after diabetic induction, and showed no stimulated C-peptide secretion compared to nondiabetic controls (baseline: 0.479 ± 0.080 ng/mL [mean ± SEM] vs after procedure: 0.219 ± 0.055 ng/mL [mean ± SEM], P = 0.02). Diabetic animals were maintained on daily insulin. Despite an initial decline in body weight acutely after pancreatectomy and streptozotocin administration, the mean body weight increased after induction over the approximately 88-day study, indicating that the animals were in good health. CONCLUSION: This stringent porcine model of diabetic induction should be used to assess autograft transplantation safety and efficacy.

Short- and long-term outcomes of third liver transplantation at single centre.

PURPOSE: Although three or more liver transplantation (LT)s in the same patient arouse not only medical but also ethical issues in the context of organ shortage, it is a fact that additional liver retransplantation (reLT) is the only lifesaving treatment option for those with graft failure after a second LT. However, little is known regarding the risks and benefits associated with a third LT. METHODS: We analyzed fifteen cases of third LT and 48 of second LT performed between January 2000 and December 2010. Clinical outcomes were compared with those of second LT cases performed during the same period. RESULTS: Model for end-stage liver disease (MELD) scores at transplant was similar between the two groups. As for surgical aspects, there was no significant difference in operative time or number of units of red blood cells transfused during the transplant procedures between the groups. Patient and graft survival after the third LT at 1, 3, and 10 years were 66.7, 51.9, and 44.4 %, and 66.7, 51.9, and 29.6 %, respectively. There was no significant difference in patient or graft survival between the groups. However, graft loss within 3 months after the third LT was significantly higher than that of second LT patients. CONCLUSION: Third LT cases showed acceptable short- and long-term outcomes that were not significantly inferior to those of a second LT. Careful patient care especially in the early phase after a third LT may be essential to improve the outcome.

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

BACKGROUND: Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. METHODS: A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. RESULTS: Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. CONCLUSIONS: There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Elective and emergency abdominal surgery in patients 90 years of age or older.

BACKGROUND: Few studies have examined perioperative outcomes in nonagenarians undergoing abdominal surgery, and fewer have reported on 1-year mortality. Our objectives were to determine the outcomes of abdominal surgery in nonagenarians and to assess the performance of Physiologic and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) and Portsmouth-POSSUM (p- POSSUM) as predictors of mortality. METHODS: We conducted a retrospective chart review of all patients 90 years and older who underwent abdominal surgery between 2000 and 2007 at a tertiary care hospital. RESULTS: We included 145 patients (median age 91, range 90-101 yr). The most common diagnoses were colorectal cancer (19.3%) and hernias (19.3%), and the most common procedures were bowel resection with anastomosis (25.5%) and hernia repair (18.6%). Overall in-hospital mortality was 15.2% (20.8% in the emergent group and 9.6% in the elective group; p = 0.06). The 1-year mortality (49.1% v. 27.8%; p = 0.016), complication (81.9% v. 61.6%; p = 0.007) and intensive care unit admission rates (44.4% v. 11.0%; p < 0.001) were significantly higher among emergent than elective surgical patients. The operative indications and procedures associated with the highest in-hospital mortality were large bowel obstruction (42.3%) and bowel resection with anastomosis (27.0%). Both the POSSUM and p-POSSUM scoring systems significantly overpredicted mortality, particularly in higher risk groups. CONCLUSION: Nonagenarians undergoing abdominal surgery have substantial operative morbidity and mortality, particularly in emergent surgical cases. Nearly 50% of patients who undergo emergency procedures die within 1 year after surgery. The POSSUM and p-POSSUM scoring systems were not reliable predictors of in-hospital mortality.

Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts.

BACKGROUND: An updated definition of early allograft dysfunction (EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients. This analysis did not differentiate between donation after brain death (DBD) and donation after cardiac death (DCD) allograft recipients. METHODS: We reviewed our prospectively entered database for all DBD (n=377) and DCD (n=38) liver transplantations between January 1, 2006 and October 30, 2011. The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups. RESULTS: EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients, but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD (11.5%) compared with those without EAD (16.7%) (P=0.664) or in the rate of death in recipients with EAD (3.8%) compared with those without EAD (8.3%) (P=0.565). The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7 (P=0.022). CONCLUSIONS: The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts. On initial assessment, it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts, however a study with a larger sample size of DCD allografts is needed to confirm these findings. The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure. An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.

A comparison of survival and pathologic features of non-alcoholic steatohepatitis and hepatitis C virus patients with hepatocellular carcinoma.

AIM: To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis (NASH) patients with hepatocellular carcinoma (HCC) and hepatitic C virus (HCV) patients with HCC (another group in which HCC is commonly seen) undergoing liver transplantation. METHODS: Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed. All explanted liver histology and pre-transplant liver biopsies were examined by two specialist liver histopathologists. Patient demographics, disease free survival, explant liver characteristics and HCC features (tumour number, cumulative tumour size, vascular invasion and differentiation) were compared between HCV and NASH liver transplant recipients. RESULTS: A total of 102 patients with NASH and 283 patients with HCV were transplanted. The incidence of HCC in NASH transplant recipients was 16.7% (17/102). The incidence of HCC in HCV transplant recipients was 22.6% (64/283). Patients with NASH-HCC were statistically older than HCV-HCC patients (P < 0.001). A significantly higher proportion of HCV-HCC patients had vascular invasion (23.4% vs 6.4%, P = 0.002) and poorly differentiated HCC (4.7% vs 0%, P < 0.001) compared to the NASH-HCC group. A trend of poorer recurrence free survival at 5 years was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver transplantation (P = 0.11). CONCLUSION: Patients transplanted for NASH-HCC appear to have less aggressive tumour features compared to those with HCV-HCC, which likely in part accounts for their improved recurrence free survival.

Reduction of liver ischemia reperfusion injury by silencing of TNF-α gene with shRNA.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a central mediator in the hepatic response to ischemia/reperfusion. Short hairpin RNA (shRNA) has been proven to be an effective means of harnessing the RNA interference pathway in mammalian cells. In the current study, we investigated whether silencing TNF-α gene with shRNA can prevent liver ischemic reperfusion injury (IRI). METHODS: Male BalB/c mice were randomized to TNF-α shRNA, scramble shRNA, or sham operation groups. TNF-α shRNA and scramble shRNA groups were injected 48 h before inducing IRI. IRI was induced via microaneurysm clamps applied to the left hepatic artery and portal vein. Six hours after reperfusion, IRI injury was examined by serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, MPO, and MDA level, as well as by relative quantities of TNF-α mRNA. RESULTS: TNF-α expression induced by ischemia reperfusion in the liver was significantly suppressed after treatment with TNF-α shRNA compared with the group treated with scramble shRNA (P < 0.001). Mice treated with TNF-α shRNA showed lower peak values of AST and ALT than scramble shRNA treated mice (P < 0.001). On histopathologic slides, mice treated with TNF-α shRNA had significantly less ischemia/reperfusion injury based on Suzuki score than the scramble shRNA group, 3.57 ± 2.30 and 8.83 ± 0.98 respectively (P < 0.001), while the sham group was not significantly different from the TNF-alpha shRNA group, 0 ± 0 and 3.57 ± 2.30, respectively (P = 0.075). Liver tissue MDA levels were significantly lower in mice treated with TNF-α shRNA as compared with the group treated with scramble shRNA (P < 0.01). Immunohistochemical staining for MPO was significantly lower in mice treated with TNF-α shRNA compared with the group treated with shRNA (compared with treated with scramble shRNA group.) CONCLUSIONS: Liver IRI can be minimized through gene silencing of TNF-α. This may represent a novel therapy in the setting of transplantation and in other conditions associated with IRI of the liver.

Do older patients utilize excess health care resources after liver transplantation?

INTRODUCTION: Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age ≥ 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure. AIM: To determine if patients ≥ 60 years of age utilize more health resources following liver transplantation compared with younger patients. MATERIAL AND METHODS: Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age ≥ 60 years (n = 51) and < 60 years (n = 157). The Chi-Square Test, Mantel-Haenszel Test, 2-sample test and odds ratios were calculated to ascertain associations between age and resource utilization parameters. Regression analyses were adjusted for model for end-stage liver disease score, location before surgery, diabetes mellitus, donor age, cold ischemia time, albumin, and diagnosis of hepatitis C. RESULTS: Recipients ≥ 60 years of age have similar lengths of hospitalization, re-operative rates, need for consultative services and readmission rates following liver transplantation, but have longer lengths of stay in the intensive care (hazard ratio 1.97, p = 0.03). CONCLUSION: Overall, liver transplant recipients ≥ 60 years of age utilize comparable resources following LT vs. younger recipients. Our findings have implications on cost-containment policies for liver transplantation.

Increased risk of severe recurrence of hepatitis C virus in liver transplant recipients of donation after cardiac death allografts.

BACKGROUND: In hepatitis C virus (HCV) recipients of donation after cardiac death (DCD) grafts, there is suggestion of lower rates of graft survival, indicating that DCD grafts themselves may represent a significant risk factor for severe recurrence of HCV. METHODS: We evaluated all DCD liver transplant recipients from August 2006 to February 2011 at our center. Recipients with HCV who received a DCD graft (group 1, HCV+ DCD, n=17) were compared with non-HCV recipients transplanted with a DCD graft (group 2, HCV- DCD, n=15), and with a matched group of HCV recipients transplanted with a donation after brain death (DBD) graft (group 3, HCV+ DBD, n=42). RESULTS: A trend of poorer graft survival was seen in HCV+ patients who underwent a DCD transplant (group 1) compared with HCV- patients who underwent a DCD transplant (group 2) (P=0.14). Importantly, a statistically significant difference in graft survival was seen in HCV+ patients undergoing DCD transplant (group 1) (73%) as compared with DBD transplant (group 3) (93%)(P=0.01). There was a statistically significant increase in HCV recurrence at 3 months (76% vs. 16%) (P=0.005) and severe HCV recurrence within the first year (47% vs. 10%) in the DCD group (P=0.004). CONCLUSIONS: HCV recurrence is more severe and progresses more rapidly in HCV+ recipients who receive grafts from DCD compared with those who receive grafts from DBD. DCD liver transplantation in HCV+ recipients is associated with a higher rate of graft failure compared with those who receive grafts from DBD. Caution must be taken when using DCD grafts in HCV+ recipients.

Organ donation after cardiac death: donor and recipient outcomes after the first three years of the Ontario experience.

PURPOSE: The aim of this study was to explore donor and recipient outcomes from organ donation after cardiac death (DCD) in Ontario and to examine the impact of DCD on deceased donation rates in Ontario since its implementation. METHODS: Donor data were obtained from the Trillium Gift of Life Network (TGLN) TOTAL database from June 1, 2006 until May 31, 2009. All DCDs were tracked, including unsuccessful DCD attempts during that time. For the first 36 months after DCD implementation, all Ontario solid organ transplant programs that utilized organs from DCD provided clinical outcome data at one year. Total DCD activity until December 1, 2010 was also tracked. In addition, we compared organ donation and DCD rates across all Canadian jurisdictions and the USA. RESULTS: For the first 36 months of DCD activity in Ontario, June 1, 2006 to May 31, 2009, there were 67 successful DCDs out of 87 attempted DCDs in 18 Ontario hospitals, resulting in 128 kidney, 41 liver, and 21 lung transplants. The one-year kidney patient and death-censored allograft survivals were 96 and 97%, respectively. Mean (SD) creatinine at 12 months was 150 (108) µmol·L(-1). In 26 (20%) extended criteria donors (ECD-DCD), the one-year creatinine was 206 (158) µmol·L(-1) vs 137 (80) µmol·L(-1) in 102 standard criteria donors (SCD-DCD) (P = 0.002). The one-year liver and lung allograft survivals were 78% and 70%, respectively. Since its implementation four and a half years ago, DCD has accounted for 10.9% of deceased donor activity in Ontario. In 2009, Ontario had a record number of organ donors. Of the 221 deceased donors, 37 (17%) donors were DCD. By December 1, 2010 there were 121 DCD Ontario donors resulting in > 300 solid organ transplants and accounting for 90% of all DCD activity in the country. CONCLUSION: The rapid update of DCD in Ontario can be attributed to strong proponents in the critical care and transplantation communities with continued support from Trillium Gift of Life Network (TGLN). Ontario is the only province to demonstrate growth in deceased donor rates over the last decade (25% over the last four years), which can be attributed primarily to the success of its DCD activity.

The clinical consequences of utilizing donation after cardiac death liver grafts into hepatitis C recipients.

UNLABELLED: Chronic liver failure from hepatitis C virus (HCV) remains the leading indication for liver transplantation (LT). Donation after cardiac death (DCD) donors are becoming a more frequent source of liver grafts. Hepatitis C recipients of standard donation after brain death (DBD) allografts may have inferior long-term results, and more so when expanded criteria organs are used. Given the nature of DCD grafts, a focus on the consequences to HCV recipients is of major importance. We analyzed the graft outcomes in HCV and non-HCV liver transplant recipients of DCD grafts. RESULTS: 21 patients underwent LT using a DCD grafts (9 HCV, 12 non-HCV) the donor body mass index and age was similar in both groups. One non-HCV recipient was retransplanted for primary non-function (PNF 8%). Biliary complications occurred in 22% (2/9) of the HCV group, 50% (6/12) in the non-HCV group (p = 0.21). After a mean of 19 months follow up, excellent patient and graft survival was seen in the non-HCV recipients of DCD grafts (100 and 92%, respectively). These outcomes were numerically less in HCV recipients (78, 67%). In the HCV recipients of DCD grafts, 33% (3/9) suffered graft loss, two from fatal aggressive fibrosing cholestatic (FCH) HCV and one due to ischemic cholangiopathy. CONCLUSION: Although a statistically significant difference in patient/graft survival for HCV and non-HCV recipients of DCD organs was not shown, it is clear that more dire consequences exist for HCV recipients of DCD grafts, highlighting the need for larger data sets for evaluating this patient population.