Donor Liver Biopsy Research Articles

Comparing computerized tomography indices and liver biopsy in liver transplantation donors for hepatosteatosis

Background: Selecting the right donor to achieve a successful liver transplantation is very important; thus computerized tomography and liver biopsy are frequently applied in the diagnosis of steatosis in donors. Purpose: We sought to investigate the efficacy of computerized tomography in the evaluation of hepatosteatosis in living donor liver transplantation donors. Material and methods: The living donor liver transplantation cases between January 2015 and December 2017 were screened retrospectively. The study participants were divided into three groups according to the degree of steatosis determined during LB as follows: grade 0: less than 5%, grade 1: 6% to 20%, and grade 2: greater than 20%. Using computerized tomography scans, hepatic attenuation value (CTL), hepatic attenuation value and spleen attenuation value ratio (CTL/S), and the difference between hepatic attenuation value and splenic attenuation values (CTL−S) were determined and the correlations of these indices and the findings of LB were compared. Results: Of the 60 patients (42 males, mean age: 32.4±7.7 years), 43 had grade 0, 15 had grade 1, and two had grade 2 hepatosteatosis, respectively. The CTL, CTL/S, and CTL−S cutoff values were 48.3, 1.06, and 3.2, respectively, while the sensitivity and specificity results of these cutoff values were 64.7% and 88.3%, 64.7% and 86%, and 64.7% and 86% and the area under the curve values were determined to be 0.81, 0.79, and 0.80 (p< 0.001). Conclusion: The use of these noninvasive indices can reduce the need for liver biopsy, which is an invasive procedure, as well as lessen the associated complication and cost rates. Future prospective studies are needed on this subject.

Deep learning quantification of percent steatosis in donor liver biopsy frozen sections.

BackgroundPathologist evaluation of donor liver biopsies provides information for accepting or discarding potential donor livers. Due to the urgent nature of the decision process, this is regularly performed using frozen sectioning at the time of biopsy. The percent steatosis in a donor liver biopsy correlates with transplant outcome, however there is significant inter- and intra-observer variability in quantifying steatosis, compounded by frozen section artifact. We hypothesized that a deep learning model could identify and quantify steatosis in donor liver biopsies.MethodsWe developed a deep learning convolutional neural network that generates a steatosis probability map from an input whole slide image (WSI) of a hematoxylin and eosin-stained frozen section, and subsequently calculates the percent steatosis. Ninety-six WSI of frozen donor liver sections from our transplant pathology service were annotated for steatosis and used to train (n = 30 WSI) and test (n = 66 WSI) the deep learning model.FindingsThe model had good correlation and agreement with the annotation in both the training set (r of 0.88, intraclass correlation coefficient [ICC] of 0.88) and novel input test sets (r = 0.85 and ICC=0.85). These measurements were superior to the estimates of the on-service pathologist at the time of initial evaluation (r = 0.52 and ICC=0.52 for the training set, and r = 0.74 and ICC=0.72 for the test set).InterpretationUse of this deep learning algorithm could be incorporated into routine pathology workflows for fast, accurate, and reproducible donor liver evaluation.FundingMid-America Transplant Society

Percutaneous liver biopsy before organ removal-Impact on organ allocation and costs in liver transplantation

HintergrundDer Stellenwert und die Sicherheit einer perkutanen Leberbiopsie (PLB) bei hirntoten Spendern vor Organentnahme sowie der Einfluss der PLB auf die Organallokation und die Kosten im Rahmen der Lebertransplantation (LT) in der Eurotransplant-Region (ET), werden weiterhin diskutiert.Material und MethodenEine perkutane Leberbiopsie vor Organentnahme erfolgte bei 36 hirntoten Spendern. Die Komplikationsrate, Spendercharakteristika, Ultraschallbefunde, die makroskopische Einschätzung und die histologischen Ergebnisse der PLB wurden analysiert. Zusätzlich wurde eine landesweite Umfrage unter 11 Lebertransplantationsexperten durchgeführt. Der Bedarf einer PLB und ihre Auswirkungen auf den Prozess der Organallokation wurden evaluiert. Mögliche Kosteneinsparungen wurden für verschiedene Szenarien auf der Grundlage von Kostendaten der Deutschen Stiftung Organtransplantation berechnet.ErgebnisseEs wurden keine Komplikationen durch die PLB beobachtet. Die Umfrage ergab, dass das Ergebnis der PLB einen erheblichen Einfluss auf die Allokation von Spenderorganen hat, insbesondere bei solchen mit „extended donor criteria (EDC)“. Die Kostenberechnung ergab ein enormes Kosteneinsparungspotenzial durch eine optimierte Allokation und die Vermeidung unnötiger Organentnahmen.SchlussfolgerungDie PLB ist ein sicheres Verfahren und besitzt ein enormes Potenzial für die Optimierung der Organallokation vor Organentnahme durch eine Reduzierung der kalten Ischämiezeit, Vermeidung unnötiger Verwerfungen von Spenderorganen sowie Kosteneinsparungen. Die klinische Relevanz und der Einfluss der PLB auf die Organallokation konnte durch unsere Daten herausgestellt werden.

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow-derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress-triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

The role of deceased donor liver biopsy: An analysis of 5449 liver transplant recipients.

No standard exists for the use of deceased donor liver biopsy during procurement. We sought to evaluate liver biopsy and the impact of findings on outcomes and graft utilization. A prospective observational study of donors after neurologic determination of death was conducted from 02/2012-08/2017 (16 OPOs). Donor data were collected through the UNOS Donor Management Goals Registry Web Portal and linked to theScientific Registry of Transplant Recipients (SRTR) for recipient outcomes. Recipients of biopsied donor livers (BxDL) were studied and a Cox proportional hazard analysis was used to identify independent predictors of 1-year graft survival. Data from 5449 liver transplant recipients were analyzed, of which 1791(33%) received a BxDL. There was no difference in graft or patient survival between the non-BxDL and BxDL recipient groups. On adjusted analysis of BxDL recipients, macrosteatosis (21%-30%[n=148] and >30%[n=92]) was not found to predict 1-year graft survival, whereas increasing donor age (HR1.02), donor Hispanic ethnicity (HR1.62), donor INR (HR1.18), and recipient life support (HR2.29) were. Excellent graft and patient survival can be achieved in recipients of BxDL grafts. Notably, as demonstrated by the lack of effect of macrosteatosis on survival, donor to recipient matching may contribute to these outcomes.

Hepatic Computed Tomography Volumetry for Noninvasive Detection of Hepatic Steatosis and Steatohepatitis in Living Liver Donors.

Detection of hepatic steatosis in donors is an important step for selection of a suitable liver allograft in living-donor transplant. This study aimed to investigate the role of hepatic computed tomography volumetry as a noninvasive method for detection of hepatic steatosis in living liver donors. In a cross-sectional study, individuals who had undergone liver biopsy as a pretransplant checkup before living-donor liver transplant were included. The segmental liver volumes were measured by computed tomography scan with intravenous contrast enhancement. Our study included 179 individuals. Mean total volume of the liver was 1705.2 ± 256.5 cm³ in those with steatohepatitis and 1419.4 ± 241.2 cm³ in those without steatohepatitis (P < .001). Higher total volume of the liver (odds ratio of 1.005; 95% confidence interval, 1.001-1.010; P = .012) and total liver volume-to-standard liver volume ratio (odds ratio of 1.090; 95% confidence interval, 1.021-1.163; P = .009) were independent predictors of steatohepatitis. A cutoff value of 1531 cm³ for total liver volume was a predictor of presence of steatohepatitis in liver biopsies of donors (sensitivity = 83%; specificity = 71%; area under the curve = 0.809; P < .001). Computed tomography volumetry may be considered as an auxiliary noninvasive method for estimation of hepatic steatosis/steatohepatitis and may be used as a guide to select donor candidates for liver biopsy.

247 – Deep Learning Algorithm Accurately Predicts Percent Steatosis in Donor Liver Biopsy Frozen Sections

247 – Deep Learning Algorithm Accurately Predicts Percent Steatosis in Donor Liver Biopsy Frozen Sections

The Intestinal-Liver Axis of FGF15-FGFR4-PPARα Signal Control Liver Ischemia Reperfusion Injury Through Regulating Autophagy

Background The hallmarks of liver ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver transplantation, include severe cell death that contributes to early graft failure. Emerging evidence indicates that the liver-intestine signal fibroblast growth factor 15 (FGF15)-fibroblast growth factor receptor 4 (FGFR 4) plays a critical regulatory role in liver physiology/pathology. FGF15 is secreted in the ileum and binding to FGFR4 in liver. However, the role of FGF15-FGFR4 signal in liver I/R injury remains unknown. Methods and Results Quantitative immunohistochemistry for 243 cases human donor liver biopsy at 1 hour after reperfusion showed that the FGFR4 expression significantly correlates with higher early allograft dysfunction and poor long term survival of liver transplantation recipients. In mice 70% liver I/R model, serum FGF15 and liver FGFR4 expression were 6-fold and 5-fold upregulated at 72 hour of reperfusion, respectively. Pharmacological inhibition by BLU9931 or genetic knock out of FGFR4 could protect liver injury through upregulating autophagy, and subsequently reduce mitochondrial dysfunction and endoplasmic reticulum stress. We then demonstrated FGFR4 could transcriptional down regulate autophagy by inhibition of PPARα during reperfusion. Through CHIP-seq data we identified that PPARα promoted transcription of autophagy genes (Atg3 and Atg7) by directly binding to their promoter. Knockdown either Atg3 or Atg7 abolished protective effect of BLU9931 on I/R injury. Finally in ex vivo porcine liver machine perfusion model, we confirmed that infusion Fgf15 recombinant protein aggravate liver I/R injury by inhibition of PPARα and subsequently autophagy. Conclusion This study uncovers the intestinal and liver cross talk (FGF15-FGFR4-PPARα signal) as a key role regulating liver I/R. The potently and selectively FGFR4 inhibitor BLU9931 may be used as a promising agent to ameliorate liver I/R.

Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation.Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory.The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. MethodsTwenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 μm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. ResultsAssessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. ConclusionsOil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis.

Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections. Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM. The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

Can negligible hepatic steatosis determined by magnetic resonance imaging–proton density fat fraction obviate the need for liver biopsy in potential liver donors?

The purpose of this study is to determine whether magnetic resonance (MR)-proton density fat fraction (PDFF) estimate of negligible hepatic fat percentage (<5%) can exclude significant hepatic steatosis (≥10%) in living liver donor candidates obviating the need for liver biopsy and to perform intraindividual comparisons between MR-PDFF techniques for hepatic steatosis quantification. In an ethics-approved retrospective study, 144 liver donor candidates with magnetic resonance spectroscopy (MRS) and 6-echo Dixon magnetic resonance imaging (MRI) between 2013 and 2015 were included. A subset of 32 candidates underwent liver biopsy. Hepatic fat percentage was determined using MR-PDFF and histopathology-determined fat fraction as the reference standard. A receiver operating characteristic analysis with positive predictive value, negative predictive value (NPV), sensitivity, and specificity was performed to discriminate between clinically significant steatosis (≥10%) or not (<10%) at MRS-PDFF and MRI-PDFF thresholds of 5% and 10%. Pearson correlation and Bland-Altman analyses between MRS-PDFF and MRI-PDFF were performed for intraindividual comparison of hepatic steatosis estimation. There was significant association between MRS-PDFF and MRI-PDFF with HP-FP. High NPV of 95% (95% confidence interval [CI], 78%-99%) and 100% (95% CI, 76%-100%) as well as an area under the curve of 0.90 (95% CI, 0.79-1.0) and 0.93 (95% CI, 0.84-1.0) were obtained with a cutoff threshold of 5% MRI-PDFF and MRS-PDFF, respectively, to exclude clinically significant steatosis (≥10%). Intraindividual comparison between MRS-PDFF and MRI-PDFF showed a Pearson correlation coefficient of 0.83. Bland-Altman analysis showed a mean difference of 1% with 95% limits of agreement between -1% and 3%. MR-PDFF estimate of negligible hepatic fat percentage (<5%) has sufficient NPV for excluding clinically significant hepatic steatosis (≥10%) in living liver donor candidates obviating the need for liver biopsy. It may be sufficient to acquire only the multiecho Dixon MRI-PDFF for hepatic steatosis estimation. Liver Transplantation 24 470-477 2018 AASLD.

Donor CD163 and nestin-positive cells predict graft function in living donor liver transplant.

To evaluate the effect of donor liver resident mesenchymal cells, M2 macrophages on liver graft outcome after living donor liver transplantation. Seventy donor biopsies were included in the study. Outcomes at day 3, 7, 30, and 180 postliver transplantation were assessed. Mesenchymal stem cells and M2 macrophages in donor liver biopsies were evaluated. Mean age of recipients was 40.9±13.6years. Sex mismatched transplants were 44 (M→F=9; F→M=35). On area under receiver operative curve analysis, donor biopsy (DB) nestin ≥3 and CD 163≥32/200x at day 3; CD163≥32 at day 7; CD 163>32, pRBC of <6.5 units at day 30, and DB nestin ≥3, CD 163≥32 and pRBC<6.5 units at day 180 predicted adequate graft functions. On multivariate analysis, higher DB nestin (P=.009) and lower cryoprecipitate (P=.009) usage at day 3, higher DB CD163 (P=.006) at day 7, higher DB CD163 (P=.018) and reduced transfusion of packed cell (pRBC) (P=.014) at day 30 and higher DB nestin (P=.011), higher CD163 (P=.009), and reduced pRBC (P=.045) at day 180 were the predictors of better outcome. Donor liver biopsy nestin+ and CD163+ can predict early graft outcome in living donor liver transplantation.

Liver biopsy in assessment of extended criteria donors.

The safety and liver utilization with prerecovery liver biopsy (PLB) in extended criteria liver donors are unclear. We conducted a retrospective cohort study in 1323 brain death donors (PLB = 496) from 3 organ procurement organizations (OPOs). Outcomes were complications, preempted liver recovery (PLR), and liver transplantation (LT). Additional analyses included liver-only and propensity score-matched multiorgan donor subgroups. PLB donors were older (57 versus 53 years; P < 0.001). Hepatitis C antibody positivity (14.3% versus 9.6%, P = 0.01) and liver-only donors (42.6% versus 17.5%; P < 0.001) were more prevalent. The PLB cohort had fewer complications (31.9% versus 42.3%; P < 0.001). In the PLB cohort, PLR was significantly higher (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.42-4.92) and LT lower (OR, 0.69; 95% CI, 0.52-0.91). In liver-only and propensity score-matched multiorgan donor subgroups, PLR was significantly higher (OR, 1.76; 95% CI, 1.06-2.94 and OR, 2.29; 95% CI, 1.37-3.82, respectively) without a decrease in LT (OR, 0.71; 95% CI, 0.43-1.18 and OR, 0.91; 95% CI, 0.63-1.33, respectively) in PLB subgroups. In conclusion, in extended criteria liver donors, PLB is safe and decreases futile liver recovery without decreasing LT. Increased use of PLB, especially in liver-only donors, is likely to save costs to OPOs and transplant centers and improve efficiencies in organ allocation. Liver Transplantation 24 182-191 2018 AASLD.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis on Liver Biopsy During Transplantation

BackgroundAssessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis. Materials and MethodsTwenty consecutive intraoperative donor liver biopsy specimens were evaluated by a pathologist at the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service. The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6 (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB special stain. After a 3-week washout period, only the slides stained with H&E were re-assessed for fibrosis stage by the same pathologist blinded to donor patient data. ResultsCombination H&E-CAB staging fibrosis score was higher in 20%, lower in 10%, and the same in 70% of biopsy specimens as determined using only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain alone. ConclusionsCAB staining may be performed on frozen tissue from liver biopsy during a transplantation process without a significant delay in diagnosis. Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

Donor Liver Small Droplet Macrovesicular Steatosis Is Associated With Increased Risk for Recipient Allograft Rejection.

Although donor livers with <30% large droplet macrovesicular steatosis (MaS) and/or small droplet MaS (irrespective of percentage) are considered safe to use, this consensus is based on variable definitions of MaS subtypes and/or without a reproducible scoring system. We analyzed 134 donor liver biopsies from allografts transplanted at University of California at San Francisco between 2000 and 2015 to determine whether large and/or small droplet MaS is a risk factor for poor outcomes. Large droplet MaS was defined as a fat droplet occupying greater than one half of an individual hepatocyte, with nuclear displacement, and scored as the percentage of total parenchymal area replaced by large fat droplets on ×40 magnification. Small droplet MaS was defined as 1 to several discrete fat droplets, each occupying less than one half of an individual hepatocyte, and scored as the percentage of remaining hepatocytes (ie, hepatocytes not occupied by large fat droplets) containing small fat droplets on ×200 magnification (ie, small droplet MaS is the percentage of "remaining hepatocytes" with small fat droplets, and "remaining hepatocytes" is defined as 100% minus percent large droplet MaS). Thus, total MaS equals the sum of large and small droplet MaS, which cannot exceed 100%. Electronic medical records were reviewed to determine outcomes. There was an increased risk for acute cellular rejection (hazard ratio=2.5, P=0.0108) and bile duct loss suggestive of chronic ductopenic rejection (hazard ratio=2.4, P=0.0130) in donor livers with ≥30% small droplet MaS. Large droplet MaS (up to 60%) was not associated with adverse outcomes. Patient survival was not adversely affected by steatosis. Excellent agreement on the estimation of large (weighted κ=0.682) and small droplet MaS (weighted κ=0.780) was achieved. Our approach to donor steatosis scoring can identify liver allograft recipients at increased risk for rejection and highlights the importance of distinguishing between small and large droplet MaS in this evaluation.

How to Perform Selective Liver Biopsy in Living Liver Donors Using Plain Computed Tomography

Preoperative donor liver biopsy is the criterion standard to verify the quality of a liver. However, it can cause some complications, thus this study was designed to know whether selective liver biopsy is possible or not, and to find a subgroup that does not require preoperative biopsy. We reviewed preoperative images and postoperative outcome in 118 donors from September 2013 to January 2014. Visual grading of steatosis on plain computed tomography (CT) was performed and compared steatosis on preoperative liver biopsy was done within 7 days from the CT scan. Visual grades of plain CT were 1 (n = 50, 42.4%), 2 (n = 47, 39.8%), 3 (n = 13, 11.0%), 4 (n = 7, 5.9%), and 1 (n = 1, 0.8%). Macrovesicular steatosis on liver biopsy according to visual grades were 1 (0.67 ± 1.3%), 2 (1.67 ± 1.8%), 3 (6.23 ± 6.4%), 4 (14.7 ± 16.6), and 5 (30%). Right liver grafts including right lobe, modified right lobe, and extended right lobe were procured in 106 (89.9%) donors, and 16% (17/106) of the donors were visual grades 3, 4, and 5. Eleven donors (64.7%) were accepted for right liver donation after liver biopsy, whereas 6 (35.3%) donors were deemed possible to donate right liver after weight reduction and reevaluation of steatosis. Transient hepatic dysfunction after right hepatectomy was significantly increased according to the increment of visual grade. Preoperative liver biopsy may not be necessary in visual grade 1 or 2 donors, but should be performed for grade 3 and 4 donors based on recipient's urgency so as to decide whether to proceed with right hepatectomy or not.

A fatal case of transplantation-mediated alloimmune thrombocytopenia following liver transplantation

ABSTRACTObjective and importance: Transplantation-mediated alloimmune thrombocytopenia (TMAT) occurs when leukocytes transferred in a donor organ from a patient with immune thrombocytopenia (ITP), mount a response against recipient platelets. We present the first fatal case of TMAT following liver transplantation and review its aetiology and treatment.Clinical presentation: The liver donor had ITP and died from an intracranial haemorrhage. The recipient platelet count fell to 2 × 109/l on post-operative day 2. Treatment refractory thrombocytopenia resulted in pulmonary haemorrhage and death. TMAT did not occur in a kidney recipient from the same ITP donor.Intervention: Extramedullary haematopoiesis was identified in the donor liver biopsy. Antibodies against platelet GPIb/IX were demonstrated in both donor and recipient. The thrombocytopenia was refractory to platelet transfusions, intravenous immunoglobulin, methylprednisolone, rituximab, romiplostim, plasmapheresis, vincristine and splenic artery embolization. On review of the literature, severe thrombocytopenia (<10 × 109/l) has started within 3 days of transplantation in all reported TMAT cases. Serious non-fatal bleeding was observed in 3/5 previously reported cases. The optimal treatment is unclear. TMAT should resolve as donor lymphocytes are eliminated but re-transplantation may be required in severe refractory cases. TMAT has been reported in recipients of a liver but not kidney or heart transplant from ITP donors, probably because of the greater burden of co-transplanted lymphoid tissue.Conclusion: Before using the liver of an ITP donor, the recipient’s fully informed consent is required. However, the risk of TMAT from an ITP donor is currently unknown and systematic review of donor registries is needed.

Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation.

Aims/IntroductionTo investigate whether donor liver steatosis increases the incidence of new‐onset diabetes after transplantation (NODAT) in liver transplant recipients.Materials and MethodsWe retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non‐steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients.ResultsOf the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non‐steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non‐steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025–3.073; P = 0.041).ConclusionsDonor liver steatosis increases NODAT incidence among liver transplant recipients.

Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver.

The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations. Hepatic NK cells were isolated from donor liver perfusates and biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56(bright) NK cells were Eomes(hi) T-bet(lo) , a phenotype virtually absent from peripheral blood. These NK cells express the chemokine receptor CXCR6 (chemokine (C-X-C motif) receptor 6), a marker of tissue residency, which is absent from hepatic CD56(dim) and blood NK cells. Compared to blood populations, these hepatic CD56(bright) NK cells have increased expression of activatory receptors (NKp44, NKp46, and NKG2D). They show reduced ability to produce IFN-γ but enhanced degranulation in response to challenge with target cells. This functionally distinct population of hepatic NK cells constitutes 20-30% of the total hepatic lymphocyte repertoire and represents a tissue-resident immune cell population adapted to the tolerogenic liver microenvironment.