FGF15 improves outcomes after brain dead donor liver transplantation with steatotic and non-steatotic grafts in rats.

BACKGROUND & AIMS: Donation after brain death (DBD) grafts are associated with reduced graft quality and function post liver transplantation (LT). We aimed to elucidate i) the impact of FGF15 levels on DBD grafts; ii) whether this impact resulted from altered intestinal FXR-FGF15; iii) whether administration of FGF15 to donors after brain death could confer a benefit on graft function post LT; and iv) whether FGF15 affects bile acid (BA) accumulation. METHODS: Steatotic and non-steatotic grafts from DBD donors and donors without brain death were transplanted in rats. FGF15 was administered alone or combined with either a BA (cholic acid) or a YAP inhibitor. RESULTS: Brain death induced intestinal damage and downregulation of FXR. The resulting reduced intestinal FGF15 was associated with low hepatic FGF15 levels, liver damage and regenerative failure. Hepatic FGFR4-Klb - the receptor for FGF15 - was downregulated whereas CYP7A1 was overexpressed, resulting in BA accumulation. FGF15 administration to DBD donors increased hepatic FGFR4-Klb, reduced CYP7A1 and normalized BA levels. The benefit of FGF15 on liver damage was reversed by cholic acid, whereas its positive effect on regeneration was maintained. YAP signaling in DBD donors was activated after FGF15 treatment. When a YAP inhibitor was administered, the benefits of FGF15 on regeneration were abolished, whereas its positive effect on hepatic damage remained. Neither the Hippo-YAP-BA nor the BA-IQGAP1-YAP axis was involved in the benefits of FGF15. CONCLUSION: Alterations in the gut-liver axis contribute to the reduced quality of DBD grafts and the associated pathophysiology of LT. FGF15 pre-treatment in DBD donors protected against damage and promoted cell proliferation. LAY SUMMARY: After brain death, potential liver donors have reduced intestinal FXR, which is associated with reduced intestinal, circulatory and hepatic levels of FGF15. A similar reduction in the cell-surface receptor complex Fgfr4/Klb is observed, whereas CYP7A1 is overexpressed; together, these molecular events result in the dangerous accumulation of bile acids, leading to damage and regenerative failure in brain dead donor grafts. Herein, we demonstrate that when such donors receive appropriate doses of FGF15, CYP7A1 levels and hepatic bile acid toxicity are reduced, and liver regeneration is promoted.

Update on liver transplantation-newer aspects

Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well as for certain early-stage liver tumors. Currently, the greatest challenge facing LT is the simple fact that there are not enough adequate livers for all the potential patients that could benefit from LT. Despite efforts to expand the donor pool to include living and deceased donors, organ shortage is still a major problem in many countries. To solve this problem, the use of marginal liver grafts has become an inevitable choice. Although the definition of marginal grafts or criteria for expanded donor selection has not been clarified yet, they are usually defined as grafts that may potentially cause primary nonfunction, impaired function, or late loss of function. These include steatotic livers, older donors, donors with positive viral serology, split livers, and donation after cardiac death (DCD). Therefore, to get the best outcome from these liver grafts, donor-recipient selection should be vigilant. Alcohol- related liver disease (ALD) is one of the most common indications for LT in Europe and North America. Traditionally, LT for alcoholic liver disease was kept limited for patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Besides, the initial results of early liver transplantation (ELT) without waiting for 6 months of abstinence period are satisfactory in severe alcoholic hepatitis (SAH). It will be important to take care of these patients from a newer perspective.

The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

BACKGROUND & AIMS: Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. METHODS: Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. RESULTS: Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. CONCLUSIONS: Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. RESULTS: Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION: Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Modified technique for aortic cross-clamping during liver donor procurement.

Undue tension on the donor vessels during organ procurement is associated with intimal dissection, which can form the nidus for the thrombosis of the hepatic artery (HA) and graft loss. According to the US OPTN database, 143 grafts were discarded in the last 15 yr due to vascular damage during procurement. The most common technique to expose the supraceliac aorta is dissection between the left lateral segment of the liver and the esophagus-stomach. In obese donors, due to restricted space and in pediatric donors where the vessels are very delicate and this space is very small, the replaced or accessory left HA(R/A LHA) is prone to damage if approached conventionally. We describe a technique for the exposure of the supraceliac aorta in which the aorta is approached from the left side behind the gastroesophageal junction that does not require division of the gastrohepatic ligament. From May 2007 to May 2013, 104 liver procurements were performed. Eighty-nine (85.6%) were adults, and 15 (14.4%) were pediatric donors. Twenty-three (22.1%) had R/A LHA. No donor organ suffered any damage. One adult recipient with R/A LHA suffered HA thrombosis not related to it. In summary, this technical modification offers improved safety during cadaveric procurement and increases the ease.

Porcine acellular dermal matrix for delayed abdominal wall closure after pediatric liver transplantation.

Children are one of the groups with the highest mortality rate on the waiting list for LT. Primary closure of the abdominal wall is often impossible in the pediatric population, due to a size mismatch between a large graft and a small recipient. We present a retrospective cohort study of six pediatric patients, who underwent delayed abdominal wall closure with a biological mesh after LT, and in whom early closure was impossible. A non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) Reconstructive Tissue Matrix; LifeCell Corp, Bridgewater, NJ, USA) was used in all of the cases of the series. After a mean follow-up of 26 months (21-32 months), all patients were asymptomatic, with a functional abdominal wall after physical examination. Non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) ) is a good alternative for delayed abdominal wall closure after pediatric LT. Randomized controlled trials are necessary to determine the best moment and the best technique for abdominal wall closure.

Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts.

BACKGROUND/AIMS: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. METHODS: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. RESULTS: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). CONCLUSION: FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Native portal vein embolization for persistent hyperoxaluria following kidney and auxiliary partial liver transplantation.

Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM-R). Following initial combined APLT-KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM-R could be corrected by trans-hepatic native PVE. The resulting increased APLT/NLM-R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT-KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function.

Adiponectin and resistin protect steatotic livers undergoing transplantation.

BACKGROUND & AIMS: Numerous steatotic livers are discarded for transplantation because of their poor tolerance to ischemia-reperfusion. Controversial roles for adiponectin and related adipocytokines visfatin and resistin have been described in different liver pathologies, nevertheless it is unknown their possible implication in ischemia-reperfusion injury associated with liver transplantation. Our study aimed at characterizing the role of the adiponectin-derived molecular pathway in transplantation with steatotic and non-steatotic liver grafts. METHODS: Steatotic and non-steatotic liver transplantation was carried out and the hepatic levels of adiponectin, visfatin and resistin were measured and modulated either pharmacologically or surgically. RESULTS: Steatotic liver grafts exhibited downregulation of both adiponectin and resistin when subjected to transplantation. Adiponectin pre-treatment only protected steatotic grafts and did it so through a visfatin-independent and resistin-dependent mechanism. Adiponectin-derived resistin accumulation activated the PI3K/Akt pathway, unravelling AMPK as an upstream mediator of adiponectin's actions in steatotic grafts. Strategies aimed at increasing adiponectin including either AMPK activators or the induction of ischemic preconditioning (which activates AMPK) increased resistin accumulation, prevented the downregulation of PI3K/Akt pathway and protected steatotic liver grafts. Conversely, PI3K/Akt pathway upregulation and hepatic protection induced by adiponectin were abolished when resistin action was inhibited. CONCLUSIONS: Our findings reveal a new protective pathway in steatotic liver transplantation, namely AMPK-adiponectin-resistin-PI3K/Akt, which may help develop new strategies aimed at increasing either adiponectin or resistin in the steatotic liver undergoing transplant to ultimately increase organ donor pool and reduce waiting list.

Ascending aorta cannulation for isolated liver procurement in extended criteria donors: a safe option in case of massive infrarenal aortic atherosclerosis.

The chronic organ shortage and the increased number of patients on the waiting list for liver transplantation have led to a progressive increase in the use of extended criteria donors. Nowadays more and more overweight donors with several comorbidities are selected for donation providing acceptable patient and liver graft survival. These donors have often aortic atherosclerosis which can spare the hepatic artery making suitable the liver for procurement. Massive aortic atherosclerosis localized to infrarenal aorta can challenge aortic cannulation for organ cooling. We herein describe in a stepwise approach the aortic cannulation realized at the ascending aorta level in case of massive infrarenal aortic atherosclerosis in ECD donors. This technique represents a safe option when abdominal aorta is not suitable for cannulation and it should be included into the surgical armamentarium of liver transplant surgeon.

NO-IL-6/10-IL-1ß axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats.

Introduction: Brain death (BD) and steatosis are both risk factors for organ dysfunction or failure in liver transplantation (LT). Material and methods: Here, we examine the role of interleukin 6 (IL- 6) and IL-10 in LT of both non-steatotic and steatotic liver recovered from donors after brain death (DBDs), as well as the molecular signaling pathways underlying the effects of such cytokines. Results: BD reduced IL-6 levels only in nonsteatotic grafts, and diminished IL-10 levels only in steatotic ones. In both graft types, BD increased IL-1ß, which was associated with hepatic inflammation and damage. IL-6 administration reduced IL-1ß only in non-steatotic grafts and protected them against damage and inflammation. Concordantly, IL-1ß inhibition via treatment with an IL-1 receptor antagonist caused the same benefits in non-steatotic grafts. Treatment with IL-10 decreased IL-1ß only in steatotic grafts and reduced injury and inflammation specifically in this graft type. Blockading the IL-1ß effects also reduced damage and inflammation in steatotic grafts. Also, blockade of IL-1ß action diminished hepatic cAMP in both types of livers, and this was associated with a reduction in liver injury and inflammation, then pointing to IL-1ß regulating cAMP generation under LT and BD conditions. Additionally, the involvement of nitric oxide (NO) in the effects of interleukins was evaluated. Pharmacological inhibition of NO in LT from DBDs prompted even more evident reductions of IL-6 or IL-10 in non-steatotic and steatotic grafts, respectively. This exacerbated the already high levels of IL-1ß seen in LT from DBDs, causing worse damage and inflammation in both graft types. The administration of NO donors to non-steatotic grafts potentiated the beneficial effects of endogenous NO, since it increased IL-6 levels, and reduced IL-1ß, inflammation, and damage. However, treatment with NO donors in steatotic grafts did not modify IL-10 or IL-1ß levels, but induced more injurious effects tan the induction of BD alone, characterized by increased nitrotyrosine, lipid peroxidation, inflammation, and hepatic damage. Conclusion: Our study thus highlights the specificity of new signaling pathways in LT from DBDs: NO-IL-6-IL-1ß in non-steatotic livers and NO-IL-10-IL-1ß in steatotic ones. This opens up new therapeutic targets that could be useful in clinical LT.

National Liver Allocation Policy-Consensus Document by the Liver Transplantation Society of India for a Nationally Uniform System of Allocation of Deceased Donor Liver Grafts.

Background: Deceased donor liver transplantation (DDLT) is increasing in India and now constitutes nearly one-third of all liver transplantation procedures performed in the country. There is currently no uniform national system of allocation of deceased donor livers. Methods: A national task force consisting of 19 clinicians involved in liver transplantation from across the country was constituted under the aegis of the Liver Transplantation Society of India to develop a consensus document addressing the above issues using a modified Delphi process of consensus development. Results: The National Liver Allocation Policy consensus document includes 46 statements covering all aspects of DDLT, including minimum listing criteria, listing for acute liver failure, DDLT wait-list management, system of prioritisation based on clinical urgency for adults and children, guidelines for allocation of paediatric organs and allocation priorities for liver grafts recovered from public sector hospitals. Conclusion: This document is the first step in the setting up of a nationally consistent policy of deceased donor liver allocation.

The Role of Neuregulin-1 in Steatotic and Non-Steatotic Liver Transplantation from Brain-Dead Donors.

BACKGROUND: Brain death (BD) and steatosis are key risk factors to predict adverse post-transplant outcomes. We investigated the role of Neuregulin-1 (NRG1) in rat steatotic and non-steatotic liver transplantation (LT) from brain death donors (DBD). METHODS: NRG1 pathways were characterized after surgery. RESULTS: NRG1 and p21-activated kinase 1 (PAK1) levels increased in steatotic and non-steatotic grafts from DBDs. The abolishment of NRG1 effects reduced PAK1. When the effect of either NRG1 nor PAK1 was inhibited, injury and regenerative failure were exacerbated. The benefits of the NRG-1-PAK1 axis in liver grafts from DBDs were associated with increased vascular endothelial growth factor-A (VEGFA) and insulin growth factor-1 (IGF1) levels, respectively. Indeed, VEGFA administration in non-steatotic livers and IGF1 treatment in steatotic grafts prevented damage and regenerative failure resulting from the inhibition of either NRG1 or PAK-1 activity in each type of liver. Exogenous NRG1 induced greater injury than BD induction. CONCLUSIONS: This study indicates the benefits of endogenous NRG1 in liver grafts from DBDs and underscores the specificity of the NRG1 signaling pathway depending on the type of liver: NRG1-PAK1-VEGFA in non-steatotic livers and NRG1-PAK1-IGF1 in steatotic livers. Exogenous NRG1 is not an appropriate strategy to apply to liver grafts from DBD.

Volumetric assessment of hepatic grafts using a light detection and ranging system for 3D scanning: Preliminary data.

BACKGROUND: Liver transplantation has evolved into a safe life-saving operation and remains the golden standard in the treatment of end stage liver disease. The main limiting factor in the application of liver transplantation is graft shortage. Many strategies have been developed in order to alleviate graft shortage, such as living donor partial liver transplantation and split liver transplantation for adult and pediatric patients. In these strategies, liver volume assessment is of paramount importance, as size mismatch can have severe consequences in the success of liver transplantation. AIM: To evaluate the safety, feasibility, and accuracy of light detection and ranging (LIDAR) 3D photography in the prediction of whole liver graft volume and mass. METHODS: Seven liver grafts procured for orthotopic liver transplantation from brain deceased donors were prospectively measured with an LIDAR handheld camera and their mass was calculated and compared to their actual weight. RESULTS: The mean error of all measurements was 17.03 g (range 3.56-59.33 g). Statistical analysis of the data yielded a Pearson correlation coefficient index of 0.9968, indicating a strong correlation between the values and a Student's t-test P value of 0.26. Mean accuracy of the measurements was calculated at 97.88%. CONCLUSION: Our preliminary data indicate that LIDAR scanning of liver grafts is a safe, cost-effective, and feasible method of ex vivo determination of whole liver volume and mass. More data are needed to determine the precision and accuracy of this method.

Elastography in the evaluation of liver allograft.

Elastography is an established technique in the evaluation of chronic liver diseases. While there is a large clinical experience and data available regarding the performance of elastography in native liver, elastography experience with liver grafts is limited and still growing. Both ultrasound-based elastography techniques and MR Elastography (MRE) are useful in the assessment of liver fibrosis in liver transplants. Technical modifications for performing elastography will be required for optimum evaluation of the graft. In general, caution needs to be exercised regarding the use of elastography immediately following transplantation as post-operative changes, perioperative conditions/complications, inflammation, and rejection can cause increased stiffness in the graft. In the follow-up, detection of increased stiffness with elastography is useful for predicting development of fibrosis in the graft. Adjunctive MRI or ultrasound with Doppler also provides comprehensive evaluation of anatomy, vascular anastomosis and patency, biliary tree, and stiffness for fibrosis. In this review, we provide a brief overview of elastography techniques available followed by the literature review of elastography in the evaluation of grafts and illustration with clinical examples.

Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors.

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

HBV-infection rate and long-term outcome after liver-transplantation of anti-HBc-positive liver-grafts to HBV-naïve recipients: A retrospective study.

BACKGROUND: Anti-HBc only positive liver grafts may be suitable for HBV-naive recipients insofar as an appropriate infection prophylaxis is performed. Therefore, we investigated the effect of prophylactic regimens on HBV infection prevention and long-term outcome of anti-HBc-positive graft recipients. PATIENTS AND METHODS: This retrospective monocenter study consisted of a cohort of 1912 patients who underwent deceased donor liver transplantation at our transplant center between June 1987 and July 2019. 81 HBV-naïve patients after reception of an anti-HBc-positive liver-graft and consecutive HBV prophylaxis were selected for further examination. HBV infection rate and host- and graft-survival rates were compared to a matched control group consisting of 162 HBV-naïve patients after reception of anti-HBc-negative grafts. Pharmaceutical HBV prophylaxis included: only HBIG, only NUCs, or combined HBIG and NUCs. RESULTS: Compared to control cases of HBV-naïve anti-HBc-negative graft recipients, no differences in host- and graft-survival rate were determined.13 of 81 anti-HBc-positive graft recipients (16%) developed HBV-infection after liver transplantation. No patient suffered from HBV infection after receiving modern NUCs. Survival analysis showed no statistical differences between patients with and without infection concerning host- and graft-survival. CONCLUSION: Especially in times of organ shortage, anti-HBc-positive liver grafts may be useful for liver transplantation in HBV-naïve recipients. Efficient prophylactic regimens can prevent HBV-infection.

Current Status of Liver Transplantation Using Marginal Grafts.

The use of marginal liver grafts has become an inevitable option because of the continuous increase in the number of patients awaiting liver transplantation and the severe shortage of suitable donors. Recently, several approaches have been adapted to expand the donor pool and improve the outcome of marginal grafts in both deceased and living donor liver transplantation. Accordingly, this review discusses the various types of marginal grafts in both deceased and living donor liver transplantation, their outcome and the up-to-date innovations or strategies to extend the donor pool and improve the patient and graft survival post-transplant.

Transient elastography for assessment of fibrosis and steatosis of liver grafts from brain-death donors.

BACKGROUND: An objective and accurate evaluation of liver grafts is required to improve the prognosis of liver transplant recipients and to increase the number of available liver grafts. AIM: To compare outcomes using FibroScan with that of pathology in liver grafts from brain-dead donors (DBD). METHODS: Liver grafts from 52 DBD were examined using ultrasound (US), FibroScan before liver transplantation (LT). Blood tested before LT and a biopsy was performed pre- or intra-operation to determine pathology. The diagnostic accuracy of the FibroScan results was compared with the pathology results, which is the gold standard for evaluating liver grafts. The donors enrolled were grouped by the stage of liver fibrosis (F0-F4) and steatosis (S0-S3), based on Kleiner's scoring system of nonalcoholic fatty liver disease, respectively. RESULTS: The liver stiffness (LS) value in group F1 was significantly increased compared with group F0 (8.74±1.32kPa and 5.93±1.64kPa, respectively, P<0.01). The LS value had a significant positive correlation with the liver graft fibrosis stage (r=0.73, P<0.01). The area under receiver operating characteristic curves (AUROC) for F1 stage fibrosis was 0.93 (P<0.01). Significant differences in the controlled attenuation parameter (CAP) were found among groups S0, S1, and S2 (173.30±38.36dB/m, 230.29±23.27dB/m, 250.00±57.01dB/m, respectively; F=12.41, P<0.01). The CAP was associated with the liver graft steatosis stage (r=0.64, P<0.01). The AUROC for S1 and S2 stage steatosis in liver grafts was 0.89 (P=0.002) and 0.83 (P=0.007), respectively. CONCLUSIONS: Transient elastography quantifies fibrosis and steatosis in liver grafts from 52 DBD with a high diagnostic accuracy and provides further imaging evidence for use in assessing liver grafts.