De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Days alive and out of hospital after liver transplant: comparing a patient-centered outcome between recipients of grafts from donation after circulatory and brain deaths.

We retrospectively compared outcomes between recipients of donation after circulatory death (DCD) and donation after brain death (DBD) liver allografts using days alive and out of hospital (DAOH), a composite outcome of mortality, morbidity, and burden of care from patient perspective. The initial length of stay and duration of any subsequent readmission for the first year after liver transplantation were recorded. Donor category and perioperative and intraoperative characteristics pertinent to liver transplantation were included. The primary outcome was DAOH365. Secondary outcomes included early allograft dysfunction and hepatic arterial and biliary complications. Although the incidence of both early allograft dysfunction (P < .001) and ischemic cholangiopathy (P < .001) was significantly greater in the recipients of DCD, there were no significant differences in the length of stay and DAOH365. The median DAOH365 was 355 days for recipients of DBD allografts and 353 days for recipients of DCD allografts (P = .34). Increased transfusion burden, longer cold ischemic time, and non-White recipients were associated with decreased DAOH. There were no significant differences in graft failure (P = .67), retransplantation (P = .67), or 1-year mortality (P = .96) between the 2 groups. DAOH is a practical and attainable measure of outcome after liver transplantation. This metric should be considered for quality measurement and reporting in liver transplantation.

Liver transplant outcomes using late allocation grafts.

Post-cross clamp late allocation (LA) liver allografts are at increased risk for discard for many reasons including logistical complexity. Nearest neighbor propensity score matching was used to match 2 standard allocation (SA) offers to every 1 LA liver offer performed at our center between 2015 and 2021. Propensity scores were based on a logistic regression model including recipient age, recipient sex, graft type (donation after circulatory death vs. donation after brain death), Model for End-stage Liver Disease (MELD), and DRI score. During this time, 101 liver transplants (LT) were performed at our center using LA offers. In comparing LA and SA offers, there were no differences in recipient characteristics including indication for transplant ( p = 0.29), presence of PVT ( p = 0.19), TIPS ( p = 0.83), and HCC status ( p = 0.24). LA grafts came from younger donors (mean age 43.6 vs. 48.9 y, p = 0.009) and were more likely to come from regional or national Organ Procurement Organizations (OPOs) ( p < 0.001). Cold ischemia time was longer for LA grafts (median 8.5 vs 6.3 h, p < 0.001). Following LT, there were no differences between the 2 groups in intensive care unit ( p = 0.22) and hospital ( p = 0.49) lengths of stay, need for endoscopic interventions ( p = 0.55), or biliary strictures ( p = 0.21). Patient (HR 1.0, 95% CI, 0.47-2.15, p = 0.99) and graft (HR 1.23, 95% CI, 0.43-3.50, p = 0.70) survival did not vary between the LA and SA cohorts. One-year LA and SA patient survival was 95.1% and 95.0%; 1-year graft survival was 93.1% and 92.1%, respectively. Despite the additional logistical complexity and longer cold ischemia time, LT outcomes utilizing LA grafts are similar to those allocated by means of SA. Improving allocation policies specific to LA offers, as well as the sharing of best practices between transplant centers and OPOs, are opportunities to further help minimize unnecessary discards.

Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score.

BACKGROUND AND AIMS: The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). APPROACH AND RESULTS: Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87. CONCLUSIONS: After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.

Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts.

INTRODUCTION: Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. METHODS: 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. RESULTS: In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. CONCLUSIONS: Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.

Donation after circulatory death transplant outcomes using livers recovered by local surgeons.

Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non-TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End-Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow-up, approximately half of those requiring endoscopy were undergoing a stent-free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re-LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76-5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98-4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.

Infectious complications in acute graft-versus-host disease after liver transplantation.

Graft-versus-hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5-99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin-resistant enterococci and gram-negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia-these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired.

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors.

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7−1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7−1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients.

BACKGROUND & AIMS: Grafts from HCV-seropositive donors can now be considered for liver transplantation (LT) owing to the advent of direct-acting antivirals (DAAs). We report on our multicenter experience of transplanting liver grafts from HCV-seropositive donors into HCV-seronegative recipients. METHODS: This is a prospective multicenter observational study evaluating outcomes in adult HCV-seronegative LT recipients who received grafts from HCV-seropositive donors in 3 US centers. RESULTS: From 01/18 to 09/19, 34 HCV-seronegative LT recipients received grafts from HCV-seropositive donors (20 HCV-viremic and 14 non-viremic). Seven grafts were from cardiac-dead donors. The median MELD-Na score at allocation was 20. Six recipients underwent simultaneous liver-kidney transplant and 4 repeat LT. No recipient of an HCV-non-viremic graft developed HCV viremia. All 20 patients who received HCV-viremic grafts had HCV viremia confirmed within 3 days after LT. DAA treatment was started at a median of 27.5 days after LT. Median pre-treatment viral load was 723,000 IU/ml. All (20/20) patients completed treatment and achieved SVR12. Treatment was well tolerated with minimal adverse events. One patient developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease, despite achieving viral clearance. This patient died due to presumed infectious complications. A recipient of an HCV-non-viremic graft died with acute myocardial infarction 610 days post LT. CONCLUSIONS: Transplantation of liver grafts from HCV-seropositive donors into HCV-seronegative recipients resulted in excellent short-term outcomes. Antiviral therapy was effective and well tolerated. Careful ongoing assessment and prompt initiation of antiviral therapy are recommended. Longer term follow-up in carefully conducted clinical trials is still required to confirm these results. LAY SUMMARY: This study shows that livers from donors exposed to HCV expand the donor pool and can be used safely in patients who are seronegative for hepatitis C infection. Treatment, initiated early post transplantation, is effective and resulted in cure in all patients.

Statin Therapy and the Incidence of Thromboembolism and Vascular Events Following Liver Transplantation.

Statin therapy may reduce the risk of venous thromboembolism (VTE), which may impact solid organ transplant outcomes. We evaluated the incidence of VTE and other complications after liver transplantation stratified by hyperlipidemia status and statin use using a retrospective cohort study approach. We reviewed all primary orthotopic liver transplantation (OLT) records from January 2014 to December 2019 from our center. Intraoperative deaths were excluded. Recipient, donor clinical and demographic data were collected. We developed risk-adjusted models to assess the effect of statin use on the occurrence of VTE, hepatic artery complications (HACs), graft failure, and death, accounting for clinical covariates and competing risks. A total of 672 OLT recipients were included in the analysis. Of this cohort, 11.9% (n = 80) received statin therapy. A total of 47 patients (7.0%) had VTE events. HACs occurred in 40 patients (6.0%). A total of 42 (6.1%) patients experienced graft loss, whereas 9.1% (n = 61) of the cohort died during the study interval. Eighty OLT recipients (29.8%) were treated with statins. In the statin treated group, 0% of patients had VTE versus 7.9% of those not on statins (P = 0.02). HACs were identified in 1.2% of the statin group and 6.8% of the nonstatin group. Untreated hyperlipidemia was associated with a 2.1-fold higher risk of HACs versus patients with no hyperlipidemia status (P = 0.05). Statin therapy was associated with significantly better risk-adjusted thromboembolic event-free survival (absence of VTE, cerebrovascular accident, myocardial infarction, HACs, and death); hazard ratio, 2.7; P = 0.01. These data indicate that statin therapy is correlated with a lower rate of VTE and HACs after liver transplantation.

Interobserver Agreement for Classifying Post-liver Transplant Biliary Strictures in Donation After Circulatory Death Donors.

INTRODUCTION: Biliary strictures are a common complication of donation after circulatory death (DCD) liver transplantation (LT) and require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. Three classification systems, based on cholangiograms, have been proposed for categorizing post-LT biliary strictures. We examined the interobserver agreement for each of the three classifications. METHODS: DCD LT recipients from 2012 through March 2017 undergoing ERCP for biliary strictures were included in the study. Initial cholangiograms delineating the entire biliary tree prior to endoscopic intervention were selected. One representative cholangiogram was selected from each ERCP. Five interventional endoscopists independently viewed each anonymized cholangiogram and classified the post-LT stricture according to each of the three classification systems. The Ling classification proposes four types of post-LT strictures based on their location. The Lee classification proposes four classes based on location and number of intrahepatic strictures. The binary system classifies strictures into anastomotic or non-anastomotic types. The Krippendorff's alpha reliability estimate was used to grade the strength of agreement as "poor," "fair," "moderate," "good," or "excellent" for values between 0-0.20, 0.21-0.4, 0.41-0.6, 0.61-0.08, and 0.81-1, respectively. RESULTS: One hundred DCD LT recipients (age 57.07 ± 8.8 years; 71 males) were initially evaluated. Of these, 49 patients who underwent 206 ERCP procedures for biliary strictures were included in the analysis. One hundred thirty-nine cholangiograms were selected and subsequently classified by five endoscopists. Interobserver agreement for post-LT biliary strictures was 0.354 for Ling classification (fair agreement), 0.405 for Lee classification (fair agreement), and 0.421 for the binary classification (moderate agreement). The binary classification provided the least amount of detail regarding the location and number of biliary strictures. DISCUSSION: The currently available classification systems for assessing post-LT biliary strictures have sub-optimal interobserver agreement. A better-designed classification system is needed for categorizing post-LT biliary strictures.

Simultaneous liver-kidney transplantation from donation after cardiac death donors: an updated perspective.

Outcomes of both donation after cardiac death (DCD) liver and kidney transplants are improving. Experience in simultaneous liver-kidney transplant (SLK) using DCD donors, however, remains limited. In an updated cohort (2010-2018), outcomes of 30 DCD SLK and 131 donation after brain death (DBD) SLK from Mayo Clinic Arizona and Mayo Clinic Minnesota were reviewed. The Model for End-Stage Liver Disease score was lower in the DCD SLK group (23 vs 29, P = .01). Kidney delayed graft function (DGF) rates were similar between the 2 groups (P = .11), although the duration of DGF was longer for DCD SLK recipients (20 vs 4 days, P = .01). Liver allograft (93.3% vs 93.1%, P = .29), kidney allograft (93.3% vs 93.1%, P = .91), and patient (96.7% vs 95.4%, P = .70) 1-year survival rates were similar. At 1 year, there were no differences in the estimated glomerular filtration rate (57.7 ± 18.2 vs 56.3 ± 17.7, P = .75) or progression of fibrosis (ci) on protocol kidney biopsy (P = .67). A higher incidence of biliary complications was observed in the DCD SLK group, with ischemic cholangiopathy being the most common (10.0% vs 0.0%, P = .03). The majority of biliary complications resolved with endoscopic management. With appropriate selection, DCD SLK recipients can have results equivalent to those of DBD SLK recipients.

Perioperative and long-term outcomes of utilizing donation after circulatory death liver grafts with macrosteatosis: A multicenter analysis.

BACKGROUND: Given the potentially additive risk from using donor livers that are both steatotic and from a donation after circulatory death (DCD) donor, there is a paucity of data on the outcome of DCD liver transplantation (LT) utilizing livers with macrosteatosis. METHODS: All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona, and Mayo Clinic-Rochester from 1999 to 2019 were included (N = 714). Recipients of DCD LT were divided into 3 groups: those with moderate macrosteatosis (30%-60%), mild macrosteatosis (5%-30%), and no steatosis (<5%). RESULTS: Patients with moderate macrosteatosis had a higher rate of postreperfusion syndrome (PRS; 53.9% vs 26.2%; P = .002), postreperfusion cardiac arrest (7.7% vs 0.3%; P < .001), primary nonfunction (PNF; 7.7% vs 1.0%; P = .003), early allograft dysfunction (EAD; 70.8% vs 45.6% and 8.3%; P = .02), and acute kidney injury (AKI; 39.1% vs 19.4%; P = .02) than patients with no steatosis. No difference in any of the perioperative complications was seen between the mild macrosteatosis and the no steatosis groups except for the rate of EAD (56.8% vs 45.6%; P = .04). No difference in ischemic cholangiopathy (IC), vascular thrombosis/stenosis or graft, and patient survival was seen between the 3 groups. CONCLUSION: DCD donors with mild macrosteatosis < 30% can be utilized with no increase in perioperative complications and similar patient and graft survival compared to DCD donors with no steatosis. When utilizing DCD donors with moderate macrosteatosis higher rates of PRS, PNF, postreperfusion cardiac arrest, EAD, and AKI should be anticipated.

Outcomes of endoscopic therapy in donation after cardiac death liver transplant biliary strictures.

BACKGROUND: Biliary strictures after donation-after-cardiac-death (DCD) liver transplantation (LT) require multiple endoscopic retrograde cholangiopancreatographies (ERCP). The outcomes of endoscopic dilation and maximal stenting are not well-characterized in this high-risk population. METHODS: DCD LT recipients who underwent LT and ERCP from 2012-2018 were selected. Anastomotic and non-anastomotic strictures were treated with balloon dilation and maximal stenting. A successful stent-free trial was defined as absence of biochemical, clinical or imaging evidence of strictures on follow-up exceeding 6 months. Adverse events were defined as unplanned admission or inpatient evaluation within 7 days of ERCP. RESULTS: Forty-nine DCD LT recipients underwent ERCP and 34 patients were diagnosed with strictures (20 anastomotic). Stent-free trial was successful in 27 patients. Adverse events occurred after 20 ERCPs. Patients with anastomotic strictures required fewer stents (1.43 ± 1.37 vs 2.63 ± 1.66; P < 0.001), shorter procedure and fluoroscopy times (34.15 ± 20.9 vs 59.6 ± 30.7 minutes, P < 0.001; 5.99 ± 7.4 vs 14.73 ± 10.74 minutes, P < 0.001), fewer relapses (10% vs 57%, P = 0.003), shorter intervals between initial ERCP and stent-free success (136.9 ± 118.3 vs 399.56 ± 234.7; P = 0.003), and between LT and stent-free success (227.8 ± 171.9 vs 464.1 ± 224.6 days; P = 0.005) compared to non-anastomotic strictures. CONCLUSION: Endoscopic dilation and maximal stenting resolves biliary strictures in DCD LT recipients with sustained success and relatively few adverse events.

Fatal diffuse pulmonary fat microemboli following reperfusion in liver transplantation with the use of marginal steatotic allografts.

Organ shortage is a major cause of delayed liver transplantation and increased waitlist time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplantation. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ, with marked preservation reperfusion injury. The mechanism of diffuse fat microemboli in this setting and possible relationship to other perioperative syndromes (transfusion-related lung injury, acute kidney injury, and postreperfusion syndrome) is discussed.

Predictors of Biliary Strictures After Liver Transplantation Among Recipients of DCD (Donation After Cardiac Death) Grafts.

INTRODUCTION: Biliary strictures are a common complication among donation after cardiac death (DCD) liver transplantation (LT) recipients and may require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. We evaluated the risk factors associated with development of biliary strictures in DCD LT recipients. METHODS: DCD LT recipients who underwent transplantation from 2012 to 2017 were divided into 2 groups: (a) those with anastomotic or non-anastomotic biliary strictures who required ERCP ("stricture group") and (b) those who did not require ERCP or had cholangiograms without evidence of biliary strictures ("non-stricture group"). Clinical data, cholangiograms and laboratory values at day 0 and day 7 after LT were compared between the two groups. RESULTS: Forty-nine of the 100 DCD LT recipients underwent ERCP. Thirty-four of these 49 LT recipients had evidence of anastomotic or non-anastomotic biliary strictures (stricture group), while the remaining 66 LT recipients comprised the non-stricture group. Donor age was significantly higher in stricture group compared to non-stricture group (49.2 ± 1.8 vs 42.8 ± 1.57 years, respectively; p = 0.01). The stricture group had a significantly higher total bilirubin at day 0 (3.5 ± 0.37 vs 2.6 ± 0.21 mg/dL; p = 0.02) and INR at day 7 (1.24 ± 0.06 vs 1.13 ± 0.01; p = 0.048) compared to the non-stricture group. Multi-variate analysis demonstrated significant association between biliary strictures and total bilirubin at day 0 of LT and age of donor. CONCLUSION: Biliary strictures occur frequently in DCD LT recipients and may be associated with older age of donor. Hyperbilirubinemia immediately after transplant and higher INR in the first 7 days after transplant may predict subsequent development of biliary strictures.

Diagnosis and Management of Genetic Iron Overload Disorders.

Iron overload disorders lead to excess iron deposition in the body, which can occur as a result of genetic or secondary causes. Genetic iron overload, referred to as hereditary hemochromatosis, may present as a common autosomal recessive mutation or as one of several uncommon mutations. Secondary iron overload may result from frequent blood transfusions, exogenous iron intake, or certain hematological diseases such as dyserythropoietic syndrome or chronic hemolytic anemia. Iron overload may be asymptomatic, or may present with significant diseases of the liver, heart, endocrine glands, joints, or other organs. If treated appropriately prior to end-organ damage, life expectancy has been shown to be similar compared to matched populations. Alongside clinical assessment, diagnostic studies involve blood tests, imaging, and in some cases liver biopsy. The mainstay of therapy is periodic phlebotomy, although oral chelation is an option for selected patients.