Dysregulated metabolism of the late herpes simplex virus 1 transcriptome through the vhs-VP22 axis uncouples virus cytopathic effect and virus production.

Herpes simplex virus 1 (HSV1) expresses its genes in a classical cascade culminating in the production of large amounts of structural proteins to facilitate virus assembly. HSV1 lacking the virus protein VP22 (Δ22) exhibits late translational shutoff, a phenotype that has been attributed to the unrestrained activity of the virion host shutoff (vhs) protein, a virus-encoded endoribonuclease which induces mRNA degradation during infection. We have previously shown that vhs is also involved in regulating the nuclear-cytoplasmic compartmentalisation of the virus transcriptome, and in the absence of VP22 a number of virus transcripts are sequestered in the nucleus late in infection. Here we show that despite expressing minimal amounts of structural proteins and failing to plaque on human fibroblasts, the strain 17 Δ22 virus replicates and spreads as efficiently as Wt virus, but without causing cytopathic effect (CPE). Nonetheless, CPE-causing virus spontaneously appeared on Δ22-infected human fibroblasts, and four viruses isolated in this way had all acquired point mutations in vhs which rescued late protein translation. However, unlike a virus deleted for vhs, these viruses still induced the degradation of both cellular and viral mRNA suggesting that vhs mutation in the absence of VP22 is necessary to overcome a more complex disturbance in mRNA metabolism than mRNA degradation alone. The ultimate outcome of secondary mutations in vhs is therefore the rescue of virus-induced CPE caused by late protein synthesis, and while there is a clear selective pressure on HSV1 to mutate vhs for optimal production of late structural proteins, the purpose of this is over and above that of virus production.

Development of a portable abdominal normothermic regional perfusion (A-NRP) program in the United States.

In situ abdominal normothermic regional perfusion (A-NRP) has been used for liver transplantation (LT) with donation after circulatory death (DCD) liver grafts in Europe with excellent results; however, adoption of A-NRP in the United States has been lacking. The current report describes the implementation and results of a portable, self-reliant A-NRP program in the United States. Isolated abdominal in situ perfusion with an extracorporeal circuit was achieved through cannulation in the abdomen or femoral vessels and inflation of a supraceliac aortic balloon and cross-clamp. The Quantum Transport System by Spectrum was used. The decision to use livers for LT was made through an assessment of perfusate lactate (q15min). From May to November 2022, 14 A-NRP donation after circulatory death procurements were performed by our abdominal transplant team (N = 11 LT, N = 20 kidney transplants, and 1 kidney-pancreas transplant). The median A-NRP run time was 68 minutes. None of the LT recipients had post-reperfusion syndrome, nor were there any cases of primary nonfunction. All livers were functioning well at the time of maximal follow-up with zero cases of ischemic cholangiopathy. The current report describes the feasibility of a portable A-NRP program that can be used in the United States. Excellent short-term post-transplant results were achieved with both livers and kidneys procured from A-NRP.

Mayo Adhesive Probability (MAP) score of non-donated kidney aids in predicting post-operative renal function following donor nephrectomy.

BACKGROUND: To examine the association of preoperative Mayo Adhesive Probability (MAP) scores in the donor (MAPd) and non-donor kidneys (MAPnd) with post-donation renal function. METHODS: Three hundred thirty-one patients undergoing hand assisted laparoscopic donor nephrectomy (HALDN) were reviewed. MAPd and MAPnd were obtained. Estimated glomerular filtration rate (eGFR) was recorded preoperatively and at 1 day, 1 month, and 6 months postoperatively. RESULTS: Two hundred females and 131 males were evaluated with median BMI 26.4 kg/m2 (range 17.1-39.6) and median age 45 years (range 19-78). MAPd score was 0 for 231 patients (69.8%) and > 0 for 100 patients (30.2%). MAPnd score was 0 for 234 patients (70.7%) and > 0 for 97 patients (29.3%). The median preoperative eGFR was 86.6 ml/min/1.73m2 (range 48.8-138.4). After adjusting for preoperative eGFR, BMI, ASA score, and kidney sidedness, postoperative eGFR was associated with MAP score in the non-donated kidney (p = 0.014) but not in the donated kidney (p = 0.24). Compared to donors with MAPnd = 0, donors with a MAPnd > 0, mean eGFR was - 2.33 ml/min/1.73m2 lower at postoperative day 1 (95% CI - 4.24 to - 0.41, p = 0.018), - 3.02 ml/min/1.73m2 lower at 1 month (95% CI - 5.11 to - 0.93, p = 0.005), and - 2.63 ml/min/1.73m2 lower at 6 months postoperatively (95% CI - 5.01 to - 0.26, p = 0.030). CONCLUSIONS: MAP score > 0 in the non-donated kidney is associated with worse renal function in the 6 months following HALDN.

Intraoperative Events in Liver Transplantation Using Donation After Circulatory Death Donors.

Liver grafts from donation after circulatory death (DCD) are a source of organs to decrease wait-list mortality. While there have been lower rates of graft loss, there are concerns of an increased incidence of intraoperative events in recipients of DCD grafts. We aim to look at the incidence of intraoperative events between recipients of livers from DCD and donation after brain death (DBD) donors. We collected data for 235 DCD liver recipients between 2006 and 2017. We performed a 1:1 propensity match between these patients and patients with DBD donors. Variables included recipient age, liver disease etiology, biological Model for End-Stage Liver Disease (MELD) score, allocation MELD score, diagnosis of hepatocellular carcinoma, and year of transplantation. DCD and DBD groups had no significant differences in incidence of postreperfusion syndrome (P = 0.75), arrhythmia requiring cardiopulmonary resuscitation (P = 0.66), and treatments for hyperkalemia (P = 0.84). In the DCD group, there was a significant increase in amount of total intraoperative and postreperfusion blood products (with exception of postreperfusion packed red blood cells) utilized (P < 0.05 for all products), significant differences in postreperfusion thromboelastography parameters, as well as inotropes and vasopressors used (P < 0.05 for all infusions). There was no difference in patient (P = 0.49) and graft survival (P = 0.10) at 1, 3, and 5 years. In conclusion, DCD grafts compared with a cohort of DBD grafts have a similar low incidence of major intraoperative events, but increased incidence of transient vasopressor/inotropic usage and increased blood transfusion requirements. This does not result in differences in longterm outcomes. While centers should continue to look at DCD liver donors, they should be cognizant regarding intraoperative care to prevent adverse outcomes.

Comparison of longterm outcomes and quality of life in recipients of donation after cardiac death liver grafts with a propensity-matched cohort.

The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score-matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow-up questionnaire and short-form (SF)-12 QOL Survey administration. Median follow-up was >5 years. Graft survival at 1-, 3-, and 5-years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group (P = 0.27). Patient survival at 1-, 3-, and 5-years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group (P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively (P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non-IC group (P < 0.001) and the DBD LT group (P < 0.001); no difference in graft survival was observed between the DCD non-IC group and the DBD LT group (P = 0.50). Physical and Mental Composite Scores on the SF-12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342-351 2017 AASLD.

Outcomes of liver transplantation with liver grafts from pediatric donors used in adult recipients.

Although there is an agreement that liver grafts from pediatric donors (PDs) should ideally be used for pediatric patients, there remain situations when these grafts are turned down for pediatric recipients and are then offered to adult recipients. The present study aimed to investigate the outcomes of using these grafts for liver transplantation (LT) in adult patients. Data from all patients undergoing LT between 2002 and 2014 were obtained from the United Network for Organ Sharing Standard Analysis and Research file. Adult recipients undergoing LT were divided into 2 groups: those receiving a pediatric liver graft (pediatric-to-adult group) and those receiving a liver graft from adult donors (adult-to-adult group). A separate subgroup analysis comparing the PDs used for adult recipients and those used for pediatric recipients was also performed. Patient and graft survival were not significantly different between pediatric-to-adult and adult-to-adult groups (P = 0.08 and P = 0.21, respectively). Hepatic artery thrombosis as the cause for graft loss was higher in the pediatric-to-adult group (3.6%) than the adult-to-adult group (1.9%; P < 0.001). A subanalysis looking at the pediatric-to-adult group found that patients with a predicted graft-to-recipient weight ratio (GRWR) < 0.8 had a higher 90-day graft loss rate than those with a GRWR ≥ 0.8 (39% versus 9%; P < 0.001). PDs used for adult recipients had a higher proportion of donors with elevated aspartate aminotransferase/alanine aminotransferase (20% vs. 12%; P < 0.001), elevated creatinine (11% vs. 4%; P < 0.001), donation after cardiac death donors (12% vs. 0.9%; P < 0.001), and were hepatitis B virus core positive (1% vs. 0.3%; P = 0.002) than PDs used for pediatric recipients. In conclusion, acceptable patient and graft survival can be achieved with the use of pediatric liver grafts in adult recipients, when these grafts have been determined to be inappropriate for usage in the pediatric population. Liver Transplantation 22 1099-1106 2016 AASLD.

Simultaneous liver and kidney transplantation in elderly patients: Outcomes and validation of a clinical risk score for patient selection.

 Introduction and aim. Many transplant programs have expanded eligibility to include patients previously ineligible because of advanced age. Outcomes of simultaneous liver-kidney transplantation (SLK) in recipients with advanced age are not known. MATERIAL AND METHODS: Data from patients undergoing transplantation between 2002 and 2015 were obtained from the UNOS Standard Analysis and Research file. RESULTS: SLK recipients aged ≥ 65 years (N = 677), SLK recipients aged < 65 years (N = 4517), and recipients of liver transplant alone(LTA) aged ≥ 65 years(N = 8495) were compared. Recipient characteristics were similar between the SLK groups. Similar patient and graft survival were observed in SLK recipients aged ≥ 65 years compared to SLK recipients aged < 65 years and LTA recipients aged ≥ 65 years. Importantly, in a subgroup analysis, superior survival was seen in the SLK group aged ≥ 65 years compared to LTA recipients aged ≥ 65 years who underwent dialysis in the week prior to transplantation (p < 0.001). A prediction model of patient survival was developed for the SLK group aged ≥ 65 years with predictors including: age ≥ 70 years (3 points), calculated MELD score (-1 to 2 points), and recipient ventilator status at the time of SLK (4 points). The risk score predicted patient survival, with a significantly inferior survival seen in patients with a score ≥ 4 (p < 0.001). CONCLUSIONS: Age should not be used as a contraindication for SLK transplantation. The validated scoring system provides a guide for patient selection and can be used when evaluating elderly patients for SLK transplantation listing.

A novel objective method for deceased donor and recipient size matching in liver transplantation.

Although the consequences of implantation of a large whole liver graft into a small recipient such as compression and compromise of graft perfusion are well known, no accepted measure to aid in donor-to-recipient size matching exists. Donor liver graft and recipient native liver weights as well as donor and recipient size and amount of ascites were investigated in 1953 patients who underwent liver transplantation using deceased donor grafts between January 2002 and July 2013. We used a previously described formula for liver resections (standardized total liver volume [sTLV] = -794.41 + 1267.28 × body surface area [m(2)]) for calculating sTLV, in the current cohort of deceased liver donors. Early allograft dysfunction (EAD) and graft survival were the primary outcome measures. The formula for calculating sTLV for liver resections was validated as an accurate predictor of liver volume in the current cohort of deceased liver donors (r(2) = 0.45; P < 0.001). A cutoff point of sTLV ratio ≥ 1.25 was determined through receiver operating characteristic curves, and patients were dichotomized into 2 groups. In the sTLV ratio ≥ 1.25 group, 50% of patients developed EAD compared to 25% of patients in the sTLV ratio < 1.25 group (P < 0.001). The proportion of patients developing graft failure within 90 days was 9.6% in the sTLV ratio ≥ 1.25 group and 5.4% in the sTLV ratio < 1.25 group (P = 0.045). This study validates the use of the sTLV for prediction of actual donor liver weight in the transplant setting. Using this formula, donors with a calculated sTLV size ratio ≥ 1.25 have an increased risk of EAD and therefore caution should be used when that value is exceeded. This adjusted size ratio can be used as a decision aid when considering donor and recipient matching with potential liver organ offers.

Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations.

Surgical site infections after liver retransplantation: incidence and risk factors.

Surgical site infections (SSIs) after liver transplantation (LT) are associated with an increased risk of graft loss and death. The incidence of SSIs after LT and their risk factors have been determined for first LT but not for second LT. The importance of reporting the incidence of SSIs risk-stratified by first LT versus second LT is not known. All patients undergoing second LT at a single institution between 2003 and 2011 (n = 152) were reviewed. The Kaplan-Meier method was used to estimate the cumulative SSI incidence. Relative risks (RRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models were used to evaluate associations of potential risk factors with SSIs after second LT. Thirty-one patients developed SSIs (6 superficial SSIs, 1 deep SSI, and 24 organ/space SSIs). The cumulative incidence of SSIs 30 days after LT was 20.8% (95% CI = 14%-27%), which was slightly but not significantly higher than the previously reported incidence of SSIs after first LT at our institution between 2003 and 2008 (16%, RR = 1.32, 95% CI = 0.90-1.93, P = .16). Units of transfused red blood cells [RR (doubling) = 1.38, 95% CI = 1.02-1.86, P = .04] and hepaticojejunostomy (RR = 2.22, 95% CI = 1.05-4.72, P = .04) were the only factors associated with SSIs after second LT in single-variable analysis. The associations weakened in a multivariate analysis (P = .07 and P = .07, respectively), potentially because of the correlation of red blood cell transfusions and hepaticojejunostomy (P = .08). In conclusion, the incidence of SSIs after second LT was slightly higher but not significantly different than the published incidence of SSIs (16%) after first LT at the same institution. Significant independent risk factors for SSIs after second LT were not identified. Risk stratification for retransplantation may not be necessary when the incidence of SSIs after LT is being reported.

Personalized Pre-clinic Nursing Telemedicine Visit: An Efficient and Efficacious Approach for Bowel and Bladder Dysfunction in Children.

OBJECTIVES: To evaluate the effectiveness and efficacy of a Registered Nurse (RN) led educational pre-clinic telephone call on compliance and outcomes in children with bowel and bladder dysfunction (BBD). METHODS: A retrospective chart review of a prospectively applied protocol in a single academic institution was performed for children aged 4-17 presenting with BBD. All children underwent a pre-clinic RN telemedicine visit where they were educated on pathophysiology of BBD, provided personalized urotherapy and bowel recommendations and instructed to complete pre-clinic questionnaires and voiding diaries. Patients were evaluated by a provider 4weeks following RN call. Data collected included compliance with forms, bowel management and need for imaging/testing, medications, and biofeedback. Patients were considered to improve with urotherapy alone if they were discharged from urology without the need for medications and/or biofeedback. RESULTS: In total, 277 patients completed an RN call and 224 patients attended a provider visit between December 2020 and June 2022. Mean age was 9.4years (3:1 Female to Male ratio). During the RN call, 154 (56%) patients had bowel management initiated. Of the 224 patients seen by a provider, 69% (n = 154) had symptom improvement or resolution with urotherapy alone. Thirty-eight patients (17%) enrolled in biofeedback with 7 (3%) completing all 8 sessions. Thirty-two patients (14%) required medication for daytime bladder symptoms. CONCLUSION: Our novel RN-led pre-clinic telemedicine visit demonstrates excellent compliance and patient outcomes for children with BBD and can reduce the use of unnecessary imaging, medications, and time-consuming treatments such as biofeedback.

Impact of Perioperative Prophylaxis With Enterococcus Activity on Risk of Surgical-Site Infection After Pancreas Transplantation.

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods: We performed a retrospective cohort study of PT recipients from 2010-2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results: Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions: Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

The surgical intensive care unit optimal mobility score predicts mortality and length of stay.

OBJECTIVES: To test if the surgical intensive care unit optimal mobility score predicts mortality and intensive care unit and hospital length of stay. DESIGN: Prospective single-center cohort study. SETTING: Surgical intensive care unit of the Massachusetts General Hospital. PATIENTS: One hundred thirteen consecutive patients admitted to the surgical intensive care unit. INVESTIGATIONS: We tested the hypotheses that the surgical intensive care unit optimal mobility score independent of comorbidity index, Acute Physiology and Chronic Health Evaluation II, creatinine, hypotension, hypernatremia, acidosis, hypoxia, and hypercarbia predicts hospital mortality, surgical intensive care unit and total hospital length of stay. MEASUREMENTS AND MAIN RESULTS: Two nurses independently predicted the patients' mobilization capacity by using the surgical intensive care unit optimal mobility score the morning after admission, whereas a third nurse recorded the achieved mobilization levels of patients at the end of the day. A multidisciplinary expert team measured patients' grip strength and assessed their predicted mobilization capacity independently. Multivariate analysis revealed that the surgical intensive care unit optimal mobility score was the only independent predictor of mortality. Surgical intensive care unit optimal mobility score, hypotension, and hypernatremia (>144 mmol/L) independently predicted intensive care unit length of stay, whereas the surgical intensive care unit optimal mobility score and hypernatremia predicted total hospital length of stay. The Acute Physiology and Chronic Health Evaluation II score was not identified in the multivariate analysis. The surgical intensive care unit optimal mobility score was also a reliable and valid instrument in predicting achieved mobilization levels of patients. CONCLUSIONS: In surgical critically ill patients presenting without preexisting impairment of functional mobility, the surgical intensive care unit optimal mobility score is a reliable and valid tool to predict mortality and intensive care unit and hospital length of stay.

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors.

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole-to-cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021-1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368-21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole-to-cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts.

Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts.

Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

 Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.

A single-center experience with biliary reconstruction in retransplantation: duct-to-duct or Roux-en-Y choledochojejunostomy.

Retransplantation is the only therapy for patients who have a failing liver graft, and it can be technically challenging. Although duct-to-duct (DD) biliary reconstruction is considered standard in deceased donor orthotopic whole organ liver transplantation, Roux-en-Y (RY) choledochojejunostomy is preferred by most for biliary reconstruction in retransplantation. We performed a retrospective review of 128 patients who underwent retransplantation after a first transplant with DD biliary construction. Of these 128 patients, 83 had DD biliary reconstructions, and 45 had RY biliary reconstructions. Log-rank tests were used to compare the complication rates between the DD and RY groups, whereas multivariate Cox proportional hazards models were used to compare patient and graft survival between the groups. The median Model for End-Stage Liver Disease score at retransplantation was significantly higher in the DD group (27 versus 21, P = 0.005). The median length of follow-up was 3.3 years. The biliary complication rates were 7% and 11% in the DD group and 10% and 10% in the RY group 30 days and 1 year after retransplantation, respectively (P = 0.73). The rates of primary graft nonfunction complications, hepatic artery thrombosis complications, and reoperation did not differ significantly between groups (all P ≥ 0.37). In comparison with RY reconstruction, there was no evidence of a difference in patient survival (relative risk = 0.79, P = 0.47) or graft survival (relative risk = 0.94, P = 0.85) for patients with DD reconstruction in multivariate analysis. In conclusion, our results provide evidence that DD biliary reconstruction is feasible in liver retransplantation without increased rates of biliary complications or compromised patient and graft survival. Further studies with larger sample sizes are needed.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus.

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV(+) patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV(+) patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV(+) recipients. Seventy-seven HCV(+) patients who received DCD liver grafts were compared to 77 matched HCV(+) patients who received donation after brain death (DBD) liver grafts and 77 unmatched non-HCV patients who received DCD liver grafts. There were no differences in 1-, 3-, and 5-year patient or graft survival among the groups. Multivariate analysis showed that the Model for End-Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006-1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493-7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV(+) groups for fibrosis progression based on protocol biopsy samples up to 5 years post-transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non-1 genotypes: HR = 2.739, 95% CI = 1.047-7.143, P = 0.040). In conclusion, this match-controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV(+) patients.

Should donation after cardiac death liver grafts be used for retransplantation?

INTRODUCTION: Donation after cardiac death (DCD) donors provide an important source of livers that has been used to expand the donor pool. As a consequence of increased numbers of OLT, allograft failure due to early and late complications and disease recurrence are more commonly encountered. The only life saving treatment for patients with liver allograft failure is liver re-transplantation (LR). The use of DCD liver grafts for LR is controversial. MATERIAL AND METHODS: Between February 1998 and June 2008, 10 patients underwent LR with DCD allografts. Five (50%) patients had no post operative complications. The 30 day, 1 year, and 3 year patient survival are 80, 60, and 60%, respectively. When DCD grafts are used for sick patients with high MELD scores for LR, the patient and graft survivals are prohibitively low. CONCLUSION: We do not recommend utilization of DCD liver grafts for LR if a candidate recipient has moderate to high MELD score.