Liver Allograft Research Articles

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Hepatic allograft rejection after liver transplantation: Clinicopathological debates!

Liver transplantation (LT) represents a life-saving surgical procedure and is considered the current standard of care for the majority of patients having end-stage liver disease. As known, significant progress in organ preservation techniques, perioperative care, and strict immunosuppression protocols are associated with favorable patient/graft survival post-LT. Hence, proper evaluation of liver allograft-related complications among survivors has paid great attention, particularly the rejection sequel after LT. It is a seriously underestimated cause of allograft injury, which pushes researchers for understanding the exact pathogenesis of different types and proper time diagnosis for better management of such complications. However, it still represents a challenge because of the complexities related to diagnosis and histopathology. Hence, increasing clinical awareness with earlier diagnosis of post-LT rejection is essential through stimulating further studies. Therefore, our review will focus on the clinicopathological debates regarding liver allograft loss after transplantation.

Most Cases of Cryptogenic Cirrhosis May Be Nonobese Nonalcoholic Steatohepatitis - Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study.

Objective The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of nonalcoholic steatohepatitis (NASH) in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; p=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, p=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; p=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; p=0.04). Conclusion Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

One fits all: a highly sensitive combined ddPCR/pyrosequencing system for the quantification of microchimerism after hematopoietic and solid organ transplantation.

A combined digital droplet PCR (ddPCR)/pyrosequencing assay system was developed that demonstrated advantages applicable to multiple qualitative and quantitative molecular genetic diagnostic applications. Data for characterizing this combined approach for hematologic stem cell transplantation (HSCT) and allele quantification from graft-derived cell-free (cf) DNA in solid organ transplantation (SOT) is presented. ddPCR and pyrosequencing assays targeting 32 SNPs/markers were established. ddPCR results from 72 gDNAs of 55 patients after allogeneic HSCT and 107 plasma-cfDNAs of 25 liver transplant recipients were compared with established methods/markers, i.e.short-tandem-repeat PCR and ALT, respectively. The ddPCR results were in good agreement with the established marker. The limit of detection was 0.02 % minor allele fraction. The relationship between ddPCR andSTR-PCR was linear with R2=0.98 allowing to transfer previously established clinical STR-PCR cut-offs to ddPCR; 50-fold higher sensitivity and a variation coefficient of <2 % enable the use of low DNA concentrations (e.g. pre-sorted cells). ddPCR detected liver allograft injury at least as sensitive as ALT suggesting that ddPCR is a reliable method to monitor the transplant integrity, especially when other biomarkers are lacking (e.g. kidney). Combining pyrosequencing for genotyping and ddPCR for minor allele quantification enhances sensitivity and precision for the patient after HSCT and SOT. Theassay is designed for maximum flexibility. It is expected to be suitable for other applications (sample tracking, prenatal diagnostics, etc.).

Letter to the Editor: Can ex-situ normothermic perfusion improve graft survival among donation after circulatory death liver allografts?

To the editor, We read with great interest the manuscript by Ibeabuchi et al recently published in Liver Transplantation.1 The authors found that ex-situ normothermic liver perfusion (ENLP) improved graft survival compared to static cold storage among donation after circulatory death (DCD) liver allografts by identifying the United Network of Organ Sharing database. This was consistent with the results of a randomized trial, which confirmed that ENLP was associated with a 50% lower level of graft injury, with these benefits being greatest in the DCD subgroup.2 Besides, considering that ENLP DCDs were performed at 20 (19.8%) of the 101 centers, the authors conducted a subanalysis restricted to the 20 centers to eliminate potential baseline differences in graft outcomes related to center experience, and the results were largely unchanged. Despite this, the results should still be interpreted with caution. The number of ENLP DCDs performed among these 20 centers ranged from 1 to 10 (median: 2; interquartile range: 1–4.5). In only a few cases in each center, it was not clear in what circumstances ENLP was selected, which inevitably led to significant limitations. All the time, the time window for evaluating the feasibility of donor livers is relatively short, and the time for surgery is severely limited. These all lead to the urgency of liver transplantation and sometimes to the fact that part of the liver available for transplantation has to be wasted. The advantages of ENLP are to create a more physiological environment in vitro and maintain the normal physiological function of donor livers, which can provide opportunities for precise evaluation and intervention treatment of donor livers. ENLP intervention allows longer total preservation times, achieves higher organ use rates, and may indeed be a promising option for organ preservation in vitro.3 However, the ENLP process is relatively complex and requires advanced equipment and technological capabilities. Once problems occur in the operation process, it is likely to cause further damage to the liver. Meanwhile, ENLP does not appear to be suitable for split liver transplantation because it may increase the warm ischemia time through additional rewarming steps. Last, whether ENLP is required for the full duration of livers’ preservation or can equally well be applied after a short period of static cold storage when the livers reach the transplant center.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

Emergency retransplant for primary non-function of liver allograft.

Journal Article Emergency retransplant for primary non-function of liver allograft Get access James M Halle-Smith, James M Halle-Smith Liver Unit, Queen Elizabeth Hospital, Birmingham, UKCentre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK Search for other works by this author on: Oxford Academic Google Scholar Lewis A Hall, Lewis A Hall Centre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK Search for other works by this author on: Oxford Academic Google Scholar Angus Hann, Angus Hann Liver Unit, Queen Elizabeth Hospital, Birmingham, UKCentre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK Search for other works by this author on: Oxford Academic Google Scholar John L Isaac, John L Isaac Department of Anaesthesia and Critical care, Queen Elizabeth Hospital, Birmingham, UK Search for other works by this author on: Oxford Academic Google Scholar Nick Murphy, Nick Murphy Department of Anaesthesia and Critical care, Queen Elizabeth Hospital, Birmingham, UK Search for other works by this author on: Oxford Academic Google Scholar Keith J Roberts, Keith J Roberts Liver Unit, Queen Elizabeth Hospital, Birmingham, UKCentre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK https://orcid.org/0000-0003-1799-9829 Search for other works by this author on: Oxford Academic Google Scholar Neil Rajoriya, Neil Rajoriya Liver Unit, Queen Elizabeth Hospital, Birmingham, UKCentre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK Search for other works by this author on: Oxford Academic Google Scholar M Thamara P R Perera M Thamara P R Perera Liver Unit, Queen Elizabeth Hospital, Birmingham, UKCentre for Liver and Gastrointestinal Research, University of Birmingham, Edgbaston, UK Correspondence to: Thamara P. R. Perera, The Liver Unit, 3rd Floor Nuffield House, Queen Elizabeth Hospital, Birmingham B15 2TH, UK (e-mail: thamara.perera@uhb.nhs.uk) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, znad110, https://doi.org/10.1093/bjs/znad110 Published: 03 May 2023 Article history Received: 05 March 2023 Accepted: 06 April 2023 Published: 03 May 2023

Morphologic and immunophenotypic evaluation of liver allograft biopsies with contemporaneous serum DSA measurements.

Acute antibody mediated rejection is increasingly identified in liver allografts as a unique form of alloimmune injury associated with donor specific antibodies (DSA). This manifests pathologically as microvascular injury and C4d uptake. Despite the liver allograft's relative resistance to alloimmune injury, liver allografts are not impervious to cellular and antibody-mediated rejection. In this blinded control study, we evaluated CD163 immunohistochemistry and applied the Banff 2016 criteria for diagnosis of acute AMR on a group of indication allograft liver biopsies from DSA positive patients and compared them to indication biopsies from DSA negative controls. Most DSA positive patients were females (75%, p=.027), and underwent transplantation for HCV infection. Significant histopathological predictors of serum DSA positivity were Banff H-score (p=.01), moderate to severe cholestasis (p=.03), and CD163 score>2 (p=.029). Other morphologic features that showed a trend with DSA positivity include Banff portal C4d-score (p=.06), bile ductular reaction (p=.07), and central perivenulitis (p=.07). The odds of DSA sMFI ≥5000 was 12.5 times higher in those with a C4d score>1 than those with aC4d score≤1 (p=.04). Incidence of definite for aAMR in the DSA positive cohort was 25% (n=5), and 0% in the DSA negative cohort. A group of 5 DSA positive cases were not classifiable by the current scheme. Sinusoidal CD163, Banff H-score, and diffuse C4d are predictors of serum DSA, and facilitate recognition of histopathological features associated with serum DSA and tissue-antibody interaction.

Research Highlights.

Research Highlights.

First Report of Immunoglobulin G4-related Hepatic Inflammatory Pseudotumor in Transplanted Liver.

Immunoglobulin (Ig)G4–related hepatic inflammatory pseudotumor (IgG4-HIPT) is a rare subset of IgG4-related disease characterized by IgG4-positive plasma cell infiltration and fibrosis.1 Only 28 cases have been reported, all occurring in native livers.1-3 We report herein the first case of IgG4-HIPT developing in a transplanted liver. All ethical approval and consent procedures were approved by the Medical Ethical Committee of Icahn School of Medicine at Mount Sinai. According to the institutional guidelines, the patient’s signed privacy consent is not necessary for a single case report with deidentified patient-specific information. Our patient, who is a 62-y-old women who underwent liver transplantation for primary biliary cholangitis 14 y prior, presented with bacteremia. Laboratory tests showed normal white blood cell count, elevated gamma-glutamyl transferase 101 U/L (normal, 8–35), normal alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Blood culture was positive for methicillin-resistant Staphylococcus aureus and Klebsiella oxytoca. Serological tests for hepatitis A, B, C, and E; cytomegalovirus; and Epstein-Barr virus were negative. Serum total IgG 1654 mg/dL (normal, 586–1602) and IgG4 171 mg/dL (normal, 2–96) were elevated. Computed tomography (Figure 1A) and magnetic resonance imaging (Figure 1C–E) of the abdomen revealed a 6-cm infiltrative mass in segment 8 of the liver. A biopsy of the lesion demonstrated parenchymal collapse replaced with fibrosis and sheets of plasma cells (Figure 1F). Immunohistochemical stains showed up to 150 IgG4-positive plasma cells per high power field and an IgG4:IgG ratio of 60% (Figure 1G and H). There was no evidence of malignancy, recurrent primary biliary cholangitis, acute cellular rejection, or chronic rejection, and a diagnosis of IgG4-HIPT was rendered. Given the patient’s bacteremia, she was started on intravenous daptomycin and ertapenem. Prednisone was deferred because she was asymptomatic from the lesion. The patient was restarted on mycophenolate mofetil 1 mo postdischarge. Repeat computed tomography of the abdomen 7 mo later demonstrated the decreased size of the lesion to 2.3 cm (Figure 1B).FIGURE 1.: Radiology features (A–E). A, Contrast-enhanced computed tomography images demonstrate an infiltrative enhancing mass in segment 8 measuring 6 cm (arrow). B, Follow-up postcontrast computed tomography after 7 mo demonstrates the decreased conspicuity and size of the lesion (measuring 2.3 cm, arrow). Contrast-enhanced MRI obtained during the (C) arterial, (D) portal venous, and (E) delayed venous phases demonstrates an ill-defined lobulated infiltrative progressively enhancing mass (arrow). Microscopic and immunohistochemical features (F–H). F, The inflammatory cells consist predominantly of lymphocytes and plasma cells (arrow) (hematoxylin and eosin stain ×200). The inflammatory cells demonstrated diffuse reactivity for (G) cluster of differentiation 138 and (H) immunoglobulin G4. MRI, magnetic resonance imaging.IgG4-related disease is generally described as an autoimmune disease because the oligoclonal expansions of both activated B cells and cytotoxic CD4+ T cells were considered central to the process.4 In our case, the IgG4-HIPT developed in a liver allograft in a patient on immunosuppression (tacrolimus target trough level 2–6 ng/dL, mycophenolate mofetil 500 mg twice daily). It may seem counterintuitive that an autoimmune process may develop in such a setting. On the other hand, infections such as Escherichia coli and Klebsiella may also incite an IgG4-predominant inflammatory response.3 In our case, the patient developed bacteremia with methicillin-resistant Staphylococcus aureus and Klebsiella at the time the liver mass was noted. Bacterial translocation from the gut to the portal circulation may have provoked an intrahepatic inflammatory response. This theory was further supported by partial or complete treatment response observed in the current and prior reported cases2 upon administration of antibiotics. Diagnosing IgG4-HIPT is challenging because of its rarity and overlapping clinical and radiological features with malignancy. Because IgG4-HIPT is clinically benign, the recognition of this entity is important to avoid unnecessary treatment.

Long-term outcomes after normothermic machine perfusion in liver transplantation—Experience at a single North American center

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta’s liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our 7-year experience applying NMP to extend preservation time in liver transplantation using a “back-to-base” approach. From 2015 to 2021, 79 livers were transplanted following NMP, compared with 386 after SCS only. NMP livers were preserved for a median time of minutes compared with minutes in the SCS cohort (P < .0001). Despite this, we observed significantly improved 30-day graft survival (P = .030), although there were no differences in long-term patient survival, major complications, or biliary or vascular complications. We also found that although SCS time was strongly associated with increased graft failure at 1 year in the SCS cohort (P = .006), there was no such association among NMP livers (P = .171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.

Combination of everolimus and low-dose tacrolimus controls histological liver allograft injury as sufficiently as high-dose tacrolimus.

The combination of everolimus (EVR) and low-dose tacrolimus (lowTAC) prevents T cell-mediated rejection of liver grafts as sufficiently as high-dose tacrolimus (highTAC) and mycophenolate, but is associated with a preserved kidney function within the first years after orthotopic liver transplantation (OLT). However, none of the available studies assessed the histological pattern of graft injury or fibrosis in surveillance biopsies (svLbx). All svLbx taken under at least one month of stable immunosuppression with either EVR (aim 3-8 ng/ml) combined with lowTAC (aim 3-5 ng/ml) or highTAC (aim 5-8 ng/ml) combined with mycophenolate (500-1500 mg/day) within the first three to four years after OLT at our center were included. Patients who were switched to EVR because of insufficient control of alloreactivity were excluded. Reasons for switches to EVR were mainly malignancies before or after OLT, or chronic kidney injury. We were able to include 20 svLbx with EVR/lowTAC and 49 with highTAC/mycophenolate. Both groups had similar liver enzymes and similar kidney function. The EVR/lowTAC group exhibited lower TAC trough levels at svLbx (4.4 vs. 6.6 ng/ml; p<.001) in comparison to highTAC/mycophenolate. Histological graft injury quantified by the rejection activity index and hepatitis activity index (Ishak), as well as fibrosis were not significantly different between the EVR/lowTAC and highTAC/mycophenolate groups. Likewise, subclinical TCMR, histological criteria justifying immunosuppression minimization, and steatosis had equal prevalence in both regimens. Immunosuppression was adjusted according to the svLbx findings. Immunosuppression regimens had similarly low rates of rejection after immunosuppression reduction, when relevant graft injury was absent in the biopsy. In conclusion, EVR/lowTAC seems to control alloreactivity and histological graft injury as sufficiently as highTAC/mycophenolate within the first 3-4 years after OLT.

Can ex-situ normothermic perfusion improve graft survival compared to static cold storage among donation after circulatory death liver allografts?

Limited data suggest that ex-situ normothermic liver perfusion (ENLP) may improve the outcomes of donation after circulatory death (DCD) liver transplants compared to static cold storage (SCS). All adult DCD liver transplants performed between 2016 and 2021 were identified in the United Network of Organ Sharing database. ENLP liver transplants were compared to SCS using inverse probability of treatment weighting to balance clinical and demographic confounders. The primary analysis simulated intention-to-treat with inverse probability of treatment weighting-adjusted Cox models. Compared to SCS DCDs (N = 3,079), recipients of ENLP DCDs (N = 65) had lower Model of End Stage Liver Disease scores at transplant (16.5 v. 18.8, p = 0.033), longer wait times (468 ± 720 vs. 246 ± 467d; p < 0.001), and received livers from donors with a greater BMI (29.2 vs. 27.5; p = 0.008). ENLP preservation was associated with a lower risk of graft failure (HR 0.31 vs. SCS, 95% CI:0.12-0.86, p = 0.023) and a lower incidence of retransplantation. A sub-analysis restricted to the 20 centers performing ENLP, encompassing 946 SCS DCDs, demonstrated similar results: (HR 0.33 vs. SCS, 95% CI: 0.13-0.94, p = 0.021). Among 111 patients who required retransplantation and where the etiology of graft failure was identified, graft failure due to ischemic cholangiopathy was noted in 1 ENLP and 46 SCS. In this retrospective analysis of the early US DCD ENLP experience, there may exist a graft survival benefit to transplants performed with ENLP compared to SCS.

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice.

Early allograft dysfunction (EAD) is a severe event leading to graft failure after liver transplant (LT). Extracellular high-mobility group box-1 (HMGB1) is a damage-associated molecular pattern that contributes to hepatic ischemia-reperfusion injury (IRI). However, the contribution of intracellular HMGB1 to LT graft injury remains elusive. We hypothesized that intracellular neutrophil-derived HMGB1 from recipients protects from post-LT EAD. We generated mice with conditional ablation or overexpression of Hmgb1 in hepatocytes, myeloid cells, or both. We performed LTs and injected lipopolysaccharide (LPS) to evaluate the effect of intracellular HMGB1 in EAD. Ablation of Hmgb1 in hepatocytes and myeloid cells of donors and recipients exacerbated early allograft injury after LT. Ablation of Hmgb1 from liver grafts did not affect graft injury; however, lack of Hmgb1 from recipient myeloid cells increased reactive oxygen species (ROS) and inflammation in liver grafts and exacerbated injury. Neutrophils lacking HMGB1 were more activated, showed enhanced pro-oxidant and pro-inflammatory signatures, and reduced biosynthesis and metabolism of inositol polyphosphates (InsPs). On LT reperfusion or LPS treatment, there was significant neutrophil mobilization and infiltration into the liver and enhanced production of ROS and pro-inflammatory cytokines when intracellular Hmgb1 was absent. Depletion of neutrophils using anti-Ly6G antibody attenuated graft injury in recipients with myeloid cell Hmgb1 ablation. Neutrophil HMGB1 derived from recipients is central to regulate their activation, limits the production of ROS and pro-inflammatory cytokines, and protects from early liver allograft injury.

Reassessing Geographic, Logistical, and Cold Ischemia Cutoffs in Liver Transplantation

Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications (P = .11). There were no differences in patient (P = .88) or graft survival (P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

NAFLD: A pretransplant and post-transplant conundrum.

1_mbm16h84Kaltura.

Selecting DCD Recipients Using Predictive Indices.

Using the Organ Procurement and Transplantation Network database, we performed univariate and multivariate retrospective analyses on 4228 DCD liver allograft recipients. We identified 8 significant factors and incorporated them into the weighted RSI to predict 3-mo survival following DCD liver transplantation with a C-statistic of 0.6971. The most significant recipient risk factors were recipient serum sodium levels >150 mEq/L at transplant, recipient albumin <2.0 g/dL at transplant, and a history of portal vein thrombosis. Because Model for End-Stage Liver Disease (MELD) score components were included as individual predictors, the DCD RSI predicts survival independently of MELD. Upon comparison with 3 previous recipient risk scores-Balance of Risk, Renal Risk Index, Patient-Survival Outcomes Following Liver Transplantation-the DCD RSI was determined to be superior at selecting optimal candidates pre-DCD transplantation, yielding a C-statistic of 0.6971. After verifying the performance of predictive indices for selection of DCD recipients, the DCD RSI is best used to preselect patients for optimized outcomes after DCD transplantation. This can increase utilization of DCD donors by improving outcomes.

Normothermic machine perfusion for older transplant recipients.

Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database. The use of NMP on outcomes in elderly recipients was reviewed using both the UNOS/SRTR database (2016-2022) and institutional data (2018-2020). Characteristics and clinical outcomes were compared between the NMP and static cold (control) groups within both populations. Nationally, using the UNOS/SRTR database, we identified 165 elderly recipients from 28 centers who received a liver allograft undergoing NMP and 4270 that underwent traditional cold static storage. NMP donors were older (48.3 vs. 43.4 years, p< 0.01), had similar rates of steatosis (8.5% vs 8.5%, p= 0.58), were more likely to be from a DCD (41.8% vs 12.3%, p< 0.01), and had a higher donor risk index (DRI; 1.70 vs. 1.60, p< 0.02). NMP recipients had similar age but had a lower MELD score at transplant (17.9 vs. 20.7, p= 0.01). Despite increased marginality of the donor graft, NMP recipients had similar allograft survival and decreased length of stay, even after accounting for recipient characteristics including MELD. Institutional data showed that 10 elderly recipients underwent NMP and 68 underwent cold static storage. At our institution, NMP recipients had a similar length of stay, rates of complications, and readmissions. NMP may mitigate donor risk factors that are relative contraindications for transplantation in elderly liver recipients, increasing the donor pool. The application of NMP in older recipients should be considered.

Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts

IntroductionBroader 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. Methods1-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. ResultsIn 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. ConclusionsExcellent 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.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

Human immunodeficiency virus (HIV)-positive patients coinfected with hepatitis B virus (HBV) are eligible for liver transplantation (LT) in Africa and Southeast Asia, particularly China. However, the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT (ABOi-LT) is unknown. To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with end-stage liver disease (ESLD). We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT. The pretransplantation HIV viral load was undetectable, with no active opportunistic infections. Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses, followed by an intraoperative regimen of intravenous immunoglobulin, methylprednisolone, and basiliximab. Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil, and prednisone. At the intermediate-term follow-up, patients showed undetectable HIV viral load, CD4(+) T cell counts greater than 150 cells/μL, no HBV recurrence, and stable liver function. A liver allograft biopsy showed no evidence of acute cellular rejection. Both patients survived at 36-42 mo of follow-up. This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes, suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.