Liver Transplant Patients Research Articles

The Spillover Effects of Extending Liver Transplantation to Patients with Colorectal Liver Metastases: A Discrete Event Simulation Analysis.

Liver transplantation is an alternative treatment for patients with nonresectable colorectal cancer liver-only metastases (CRLM); however, the potential effects on wait-list time and life expectancy to other patients on the transplant waiting list have not been considered. We explored the potential effects of expanding liver transplantation eligibility to include patients with CRLM on wait-list time and life expectancy in Norway. We developed a discrete event simulation model to reflect the Norwegian liver transplantation waiting list process and included 2 groups: 1) patients currently eligible for liver transplantation and 2) CRLM patients. Under 2 alternative CRLM-patient transplant eligibility criteria, we simulated 2 strategies: 1) inclusion of only currently eligible patients (CRLM patients received standard-of-care palliative chemotherapy) and 2) expanding waiting list eligibility to include CRLM patients under 2 eligibility criteria. Model outcomes included median waiting list time, life expectancy, and total life-years. For every additional CRLM patient listed per year, the overall median wait-list time, initially 52 d, increased by 8% to 11%. Adding 2 additional CRLM patients under the most restrictive eligibility criteria increased the CRLM patients' average life expectancy by 10.64 y and decreased the average life expectancy for currently eligible patients by 0.05 y. Under these assumptions, there was a net gain of 149.61 life-years over a 10-y programmatic period, which continued to increase under scenarios of adding 10 CRLM patients to the wait-list. Health gains were lower under less restrictive CRLM eligibility criteria. For example, adding 4 additional CRLM patients under the less restrictive eligibility criteria increased the CRLM patients' average life expectancy by 5.64 y and decreased the average life expectancy for currently eligible patients by 0.12 y. Under these assumptions, there was a net gain of 96.36 life-years over a 10-y programmatic period, which continued to increase up to 7 CRLM patients. Our model-based analysis enabled the consideration of the potential effects of enlisting Norwegian CRLM patients for liver transplantation on wait-list time and life expectancy. Enlisting CRLM patients is expected to increase the total health effects, which supports the implementation of liver transplantation for CRLM patients in Norway. Given the Norwegian donor liver availability, adding patients with nonresectable colorectal cancer liver-only metastases (CRLM) to the liver transplantation waiting list had an overall modest, but varying, impact on total waiting list time.Survival gains for selected CRLM patients treated with liver transplantation would likely outweigh the losses incurred to patients listed currently.To improve the total life-years gained in the population, Norway should consider expanding the treatment options for CRLM patients to include liver transplantation.Other countries may also have an opportunity to gain total life-years by extending the waiting list eligibility criteria; however, country-specific analyses are required.

Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis

Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.

Treatment of Hyperlipidemia With Alirocumab in a Liver Transplant Recipient With Poor Blood Lipid Control: Case Report

The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, to treat drug-resistant hypercholesterolemia is increasing; however, to date there have been no studies on the use of alirocumab to treat the hyperlipidemia that follows liver transplantation. Here we report a case of successful management of hyperlipidemia, albeit without total reversal of elevated serum triglycerides, with alirocumab monotherapy in a liver transplantation patient who was resistant to rosuvastatin and fenofibrate. In terms of safety, only transient palpitations following the first few alirocumab injections were recorded. This case illustrates that alirocumab can be a viable option for patients who experience poor lipid control after liver transplantation.

Cancer screening in liver transplant patients: think about anal canal!

Cancer screening in liver transplant patients: think about anal canal!

Outcomes of liver transplant recipients with pretransplant malignancies: Insights from a single institution’s experience.

11173 Background: Increasing liver transplantation (LT) utilization has resulted in more and more patients with a history of a non-hepatobiliary malignancy. Rather than deny such patients a lifesaving therapy the benefits must be weighed against risk of tumor recurrence and de novo malignancies (DNM) post-LT, especially with the immunosuppression required. While data has been presented on outcomes of pre transplant malignancies (PTM) in kidney and heart transplants, LT data is lacking. Our aim is to characterize rates of recurrence, DNM, and overall survival (OS) post-LT at a single, high volume American center. Methods: This retrospective study at Houston Methodist Hospital included patients who underwent LT with known history of PTM. Data was extracted from electronic health records, and descriptive statistics performed. Institutional IRB approval is obtained. Results: Between 01/1999- 12/2022, 1617 LTs were performed at our institute. We identified 261 LT recipients with 297 PTM, including 91 non- and 206 hepatobiliary cancers (See Table). Follow-up period ranged from 1 to 23 years. Post-LT malignancies were observed in 66 patients, 25% of the study population. Tumor recurrences accounted for 44 (17%) cases, and DNM were seen in 22 (8%). The DNMs included skin non-melanoma (n=8 cases), head & neck (3), PTLD (2), prostate (2), renal (1), lung (1), CRC (1), pancreatic (1), gynecologic (2), and poorly differentiated (1). The OS rate at 1-, 5-years (excluding those less than 5 years follow-up and unknown), and at time of last follow-up were 86.6%, 60-65% and 70%, respectively. Patients with post-LT malignancies had lower OS compared to those without (46% vs. 77.7%). Conclusions: To our knowledge, this study is the first to assess post-LT outcomes in patients with PTM. This study of LT recipients with PTM demonstrates post-LT malignancy rates of 25%, including 17% with recurrences and 8% with DNM. The latter is within the previously reported range of 3-14% DNM in the general post-LT population and dominated by skin cancers. Post-LT OS is excellent in these recipients and comparable to all LT patients. However, OS is lower in those with post-LT malignancies, implying a possible role for increased cancer surveillance. Limitations include retrospective design and potential chart bias. Future work in this cohort will focus on immunosuppression effects for this high-risk population. [Table: see text]

Effect of liver transplants with retrograde reperfusion on early postoperative recovery of liver function and its risk factors

BackgroundThe purpose of this study was to investigate effect of liver Transplants (LT) with retrograde reperfusion on early postoperative recovery of liver function and its risk factors.MethodsWe conducted a retrospective analysis of clinical data from 136 liver transplantation (LT) patients at the 900th Hospital of the Chinese People’s Liberation Army Joint Support Army, covering the period from January 2015 to January 2021. All participants provided informed consent, adhering to medical ethics guidelines. Patients were stratified into two groups based on the liver perfusion technique used: retrograde reperfusion (RTR, n = 108) and initial portal reperfusion (IPR, n = 28). Our study focused on a subset of 23 patients from each group to compare postoperative liver function recovery. The final analysis included 86 RTR and 28 IPR cases after excluding 8 RTR patients who underwent initial hepatic artery reperfusion and 14 who received simultaneous hepatic artery and portal vein reperfusion. Further subdivision within the RTR group identified 19 patients with early hepatic allograft dysfunction (EAD) and 67 without, allowing for an assessment of the influence of preoperative and intraoperative parameters, as well as perfusion methods, on EAD incidence post-LT.ResultsAlanine aminotransferase (ALT) was 329 (211 ~ 548) and 176 (98 ~ 282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288 ~ 918) and 251 (147 ~ 430) U/L in the IPR group (Z =-1.979, -2.299, P = 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P = 0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after LT.ConclusionRTR LT is more favorable for patients’ early postoperative liver function recovery. For patients undergoing LT for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.

Productivity loss by cancer stage in patients newly diagnosed with hepatocellular carcinoma: A claims database analysis.

New cancer diagnoses are associated with employment decrease, workplace absenteeism, and attributable costs to employers. To estimate the workplace productivity loss in the year following a new diagnosis of early-, intermediate-, or advanced-stage hepatocellular carcinoma (HCC) in commercially insured US adults. We conducted a retrospective cohort study using Merative MarketScan commercial claims to identify incident HCC diagnoses from 2010 to 2020. Patients were stratified into early-, intermediate-, or advanced-stage cohorts based on presence of secondary malignancy codes or first treatment received. Mean workdays lost and attributable cost in the year following a new diagnosis were calculated using the Kaplan-Meier sample averages to account for censoring. An exploratory analysis was conducted on subgroups in the early and advanced cohorts to assess productivity loss in patients with and without treatment. Mean workdays lost in the year following a new HCC diagnosis among the early, intermediate, and advanced cohorts was 22.6 days (95% CI = 16.0-29.8), 17.4 days (95% CI = 11.9-23.2), and 19.5 days (95% CI = 15.6-23.6), respectively. Corresponding indirect costs were $6,031(95% CI = $4,270-$7,953), $4,644 (95% CI = $3,176-$6,192), and $5,204 (95% CI = $4,163-$6,298). Early-stage patients without a liver transplant and advanced-stage patients who received systemic therapy had 19.7 (95% CI = 12.7-27.4) and 22.0 (95% CI = 16.6-27.7) mean workdays lost, respectively. Productivity loss varies by stage and appears to be higher in early-stage patients who receive more intensive treatments in the first year following a new HCC diagnosis.

Nursing cooperation in orthotopic heart and liver transplantation-A case report

Nursing cooperation in orthotopic heart and liver transplantation Patients with ischemic cardiomyopathy and decompensation of alcoholic liver cirrhosis. To summarize the main points of nursing cooperation for a case of alcoholic liver cirrhosis with decompensated liver function and severe ischemic cardiomyopathy undergoing orthotopic heart-liver transplantation. It is proposed that the nurses in the operating room should have a detailed understanding of the patient’s relevant conditions and special requirements before the operation, and participate in the multidisciplinary professional team to formulate possible emergency plans

Hepatocellular Carcinoma: The Evolving Role of Systemic Therapies as a Bridging Treatment to Liver Transplantation.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Detection of inflammasome activation in liver tissue during the donation process as potential biomarker for liver transplantation

Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains the main source of donated organs, exploration of donation after circulatory death (DCD) addresses donor scarcity but introduces challenges due to warm ischemia. While technical advances have improved outcomes, challenges persist, with a 13% mortality rate within the first year. Delving into liver transplantation complexities reveals the profound impact of molecular signaling on organ fate. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation play a pivotal role, influencing inflammatory responses. The NLRP3 inflammasome, found in hepatocytes, contributes to inflammation, fibrosis, and liver cell death. This study explores these dynamics, shedding light on potential biomarkers and therapeutic targets. Samples from 36 liver transplant patients were analyzed for ASC specks detection and inflammasome-related gene expression. Liver biopsies, obtained before and after cold ischemia storage, were processed for immunofluorescence, qRT-PCR, and Western blot. One year post-LT clinical follow-up included diagnostic procedures for complications, and global survival was assessed. Immunofluorescence detected activated inflammasome complexes in fixed liver tissues. ASC specks were identified in hepatocytes, showing a trend toward more specks in DCD livers. Likewise, inflammasome-related gene expression analysis indicated higher expression in DCD livers, decreasing after cold ischemia. Similar results were found at protein level. Patients with increased ASC specks staining exhibited lower overall survival rates, correlating with IL1B expression after cold ischemia. Although preliminary, these findings offer novel insights into utilizing direct detection of inflammasome activation in liver tissue as a biomarker. They suggest its potential impact on post-transplant outcomes, potentially paving the way for improved diagnostic approaches and personalized treatment strategies in LT.

“My feelings and my thoughts are my lived experience, not the numbers they show me on a piece of paper”: Indigenous experiences of liver transplantation in British Columbia, Canada

ABSTRACT Indigenous Peoples in Canada face healthcare inequities impacting access to solid organ transplantation. The experiences of Indigenous patients during the liver transplant process, and how transplant professionals perceive challenges faced by Indigenous Peoples, has not been studied. Thirteen semi-structured qualitative interviews were conducted via telehealth with Indigenous liver transplant patients (n = 7) and transplant care providers (n = 6) across British Columbia, Canada between April 2021—May 2022. Themes were identified to inform clinical approaches and transplant care planning and validated by Indigenous health experts. Among patient participants: transplants occurred between 1992–2020; all were women; and the mean age at the time of interview was 60 years. Among transplant care provider participants: roles included nursing, social work, and surgery; 83% were women; and the median number of years in transplant care was ten. Three broad themes were identified: Indigenous strengths and resources, systemic and structural barriers, and inconsistent care and cultural safety across health professions impact Indigenous patient care during liver transplantation. This study contributes insights into systemic barriers and Indigenous resilience in the liver transplant journey. Dismantling structural barriers to early linkage to care is needed, and training for transplant clinicians on Indigenous histories, cultural protocols, and cultural safety is strongly recommended.

Microbiological and molecular studies on a multidrug-resistant Pseudomonas aeruginosa from a liver transplant patient with urinary tract infection in Egypt.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants. In this study, a number of 30 individuals who underwent liver transplants were registered. Ninety urine and 60 wound site swab samples were collected and processed for culturing, identification, and antimicrobial sensitivity. Extensively drug-resistant strain EMARA01 was confirmed through Sanger sequencing and was then processed for whole genome sequencing to characterize the genomic pattern. Sequencing data were processed for de novo assembly using various tools and databases, including genome annotation, serotype identification, virulence factor genes, and antimicrobial resistance gene. Pangenome analysis of randomly selected 147 reference strains and EMAR01 sequenced strain was performed using the Bacterial Pan Genome Analysis (BPGA) software. Of these total examined samples, nosocomial infection due to P. aeruginosa was detected in twelve patients' samples. AST analysis showed that P. aeruginosa strains exhibit resistance to tobramycin, erythromycin, and gentamicin, followed by piperacillin and ofloxacin, and no strains exhibit resistance to meropenem and imipenem. The CARD database identified 59 AMR genes similar to the EMAR01 strain genome and mostly belong to the family involved in the resistance-nodulation-cell division (RND) antibiotic efflux pump. Five genes; nalC, nalD, MexR, MexA, and MexB, exhibit resistance to 14 classes of antibiotics, while two AMR; CpxR, and OprM, exhibit resistance to 15 classes of drugs. Pangenome analysis revealed that the pan-genome remained open, suggesting the potential for acquiring accessory and unique genes. Notably, the genes predominantly involved in amino acid transport metabolism were identified using the KEGG database. This study provides valuable insights into the antimicrobial resistance profile, genetic features, and genomic evolution of P. aeruginosa strains causing UTIs in liver transplant patients. The findings emphasize the significance of comprehending AMR mechanisms and genetic diversity in P. aeruginosa for developing effective treatment strategies and infection control measures.

Assessment of Liver Transplant Eligibility in Chronic Liver Disease Patients: A Cross-Sectional Study From a Tertiary Care Hospital of Pakistan.

The burden of chronic liver disease (CLD) is increasing globally and the ultimate treatment is a liver transplant. As Pakistan is a developing country, liver transplantation is not easily available due to limited resources.This study aims to assess the patients with CLD for liver transplantation and to find the frequency of eligible candidates for liver transplantation. A cross-sectional observational study was conducted on patients with CLD from June 2022 to December 2022.Total bilirubin, serum creatinine complete blood count, serum electrolytes, and international normalised ratio (INR) were done. The Model for End-Stage Liver Disease (MELD) score was calculated and the frequency of eligible patients for liver transplant was determined. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA). In our study, 149 patients were enrolled with a mean age of 46.81±15.7 years. There were 58.7% male and 41.6% female patients. The mean duration of liver cirrhosis was 18.22±11.7 months. The mean MELD score was 20.71±5.2. The common liver cirrhosis stages were stage II and stage II was found in 32.2% of each. Hepatocellular carcinoma (HCC) was present in 15.4% of patients. There were 25.5% of patients eligible for liver transplants. In our study, we found that significant numbers of patients with CLD were eligible for liver transplantation.

#1043 Metabolomics and proteomics study on kidney function post-liver transplantation

Abstract Background and Aims Hepatorenal syndrome (HRS) is a serious complication characterized by kidney dysfunction in patients with advanced liver disease. The pathophysiology of HRS is poorly understood and involves a combination of hemodynamic, circulatory, inflammatory, and hormonal factors. While some patients with HRS restore kidney function after liver transplantation (LT), others continue to have impaired kidney function. Understanding the mechanisms associated with persistent kidney dysfunction is essential for developing effective treatments and stratifying patients for combined liver-kidney transplantation versus LT only. Method We analyzed serum samples from 10 patients of the multicenter prospective study (INAID CTOT14). Five of them had no HRS and maintained an eGFR > 50 ml/min post-LT. One patient with HRS recovered kidney function post-LT. Four patients with HRS failed to regain kidney function at one- and two-months post-LT (eGFR < 30 ml/min). We categorized the five patients without HRS and one patient with recovered eGFR as Normal Kidney Function (NKF) group and the other four patients as Impaired Kidney Function (IKF) group. Serum samples were collected at one (visit 1) and two months (visit 2) post-LT and stored at −80°C until analysis. Both untargeted metabolomics and proteomics analysis were conducted using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS) on Agilent® Q-TOF 6546. Data was analyzed by Agilent® Qualitative Workflow 10, Agilent® Profinder 10, MetaboAnalyst (V6.0), and Spectrum Mill MS software. Results A total of 150 metabolites were identified by LC-MS/MS based metabolomics. Principal component analysis (PCA) did not show significant differences between visit 1 and visit 2 samples (Fig. 1A). Therefore, visit 1 and visit 2 samples were analyzed together. With 12 samples in NKF and 8 samples in IKF group, the PCA score plot showed distinct clustering of the two groups (Fig. 1B). Volcano plot analysis was conducted to analyze metabolite differences between NKF and IKF. P-values were calculated using a Student's t-test, and differential metabolites were identified with a P-value cut-off of < .05 and a fold change > 2.0. The result revealed 37 downregulated and 13 upregulated metabolites when comparing NKF and IKF (Fig. 1C). Notably, creatinine was among the downregulated metabolites in the NKF group, validating the accuracy of our analysis. Untargeted proteomics analysis was also performed on all 20 samples. Using a P-value cut-off of .05 and a fold change >1.25, 43 proteins were found to be upregulated, and four proteins to be downregulated when comparing NKF to IKF. Fig. 2A lists the top 10 regulated proteins, with beta-2-microglobulin as the most significantly changed. Reactome® pathway analysis of these 47 proteins highlighted potential impacts on various biological pathways (Fig. 2B), providing potential valuable insights into the molecular alterations associated with kidney function post-LT. Conclusion Our comprehensive metabolomics and proteomics study characterized the molecular alterations associated with kidney function post-LT. The identified metabolites and proteins may provide valuable insights for understanding persistent kidney damage. Future research is warranted to confirm and correlate these findings with clinical outcomes, enhancing the applicability and significance of our results in the broader context of HRS and LT.

Socioeconomic deprivation is associated with worse patient and graft survival following adult liver transplantation.

The impact of social determinants of health (SDOH) on adult liver transplant recipient outcomes is not clear at a national level. Further understanding of the impact of SDOH on patient outcomes can inform effective equitable healthcare delivery. Unadjusted and multivariable models were used to analyze the Scientific Registry of Transplant Recipients to evaluate the association between the Social Deprivation Index (SDI) based on liver transplant recipient's residential location and patient and graft survival. We included adult recipients between 1/1/2008-12/1/2021. Patient and graft survival were lower in adults living in areas with deprivation scores above the median. Five-year patient and graft survival were 78.7% and 76.5% respectively in the cohort above median SDI compared to 80.5% and 78.3% below median SDI. Compared to the recipients in low deprivation residential areas, recipients residing in highest deprivation (SDI quintile=5) cohort had 6% higher adjusted risk of mortality (Adjusted Hazard Ratio [AHR]=1.06,95%C.I. 1.01-1.13) and 6% higher risk of graft failure (AHR=1.06,95% C.I. 1.001-1.11). The increased risks for recipients residing in more vulnerable residential areas were higher (AHR=1.11,95% CI 1.03-1.20 for both death and graft loss) following the first-year post-transplantation. Importantly, overall risk for graft loss associated with SDI was not linear but instead accelerated above the median level of deprivation. In the United States, SDOH, as reflected by residential distress, significantly impact 5-year patient and graft survival. The overall effect of residential deprivation are modest, but importantly, results illustrate they are more strongly associated with longer-term follow up and accelerate at higher deprivation levels. Further research is needed to evaluate effective interventions and policies to attenuate disparities in outcomes among recipients in highly disadvantaged areas.

Determining the Relationship Between Quality of Life and Perceived Stress in Liver Transplant Patients Receiving Immunosuppression Therapy

Objective: This study was conducted to evaluate the relationship between quality of life and perceived stress in liver transplant patients receiving immunosuppression therapy. Materials and Methods: This study is a cross-sectional study with the participation of 124 liver transplant patients hospitalized in the liver transplantation center of a university hospital. Results: The results of the correlation analysis between the perceived stress scale (PSS) and the 36-item Short Form Health Survey (SF-36) subscales of the participants: A negative and weak significant relationship was found between physical function, physical role difficulty, emotional role difficulty, energy/vitality, social functioning, general health perception, and pain sub-dimensions (r=-0.209 and -0.480). A negative, moderate and significant relationship was found between PSS and the mental health sub-dimension (r=-0.563). As a result of the regression analysis, the effect of the PSS total score average on SF-36 sub-dimensions was examined, and it was found that it had the highest and negative effect on the mental health sub-dimension with a rate of 31.7% (R2=.317; B=-1.962; p

Characterising the challenges of managing difficult red blood cell alloantibodies in liver transplant recipients

AimsFormation of red blood cell alloantibodies (RBCAs) complicates transfusion support in liver transplantation (LT). Difficult RBCAs (DAs, >3 antibodies or antibodies for which <25% donors are antigen negative) further challenge...

Gas6/AXL Alleviates Hepatic Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the PI3K/AKT Pathway.

Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear. A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury. Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury. AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.

Enhanced external counterpulsation treatment improves multi-organ hemodynamics for postoperative liver transplantation patient. A case report

IntroductionPost liver transplantation (LT) patients endure high morbidity rate of multi-organ ischemic symptoms following reperfusion. We hypothesize that enhanced external counterpulsation (EECP) as a typical non-invasive assisted circulation procedure, which can efficiently inhibit the relative ischemic symptoms via the systemic improvement of hemodynamics.Case presentationA 51-year-old male patient, 76 kg, 172 cm, received orthotopic LT surgery for viral hepatitis B induced acute-on-chronic liver failure hepatic failure. His medical records revealed ischemic symptoms in multi-organ at the time of hospital discharge, including headache, refractory insomnia, abdominal paralysis, and lower limb pain. The EECP treatment was introduced for assisted rehabilitation and to improve the postoperative quality of life. Doppler Ultrasound examination showed significant augmentation of blood flow volume in the carotid arteries, the hepatic artery, the portal vein and the femoral artery during EECP intervention. A standard 35-hour EECP treatment led to significant improvement in quality of life, e.g. sleep quality and walking ability.ConclusionWe report a case of multi-organ ischemic symptoms in a post LT patient. EECP treatment can significantly improve the quality of life via the systematic promotion of hemodynamics.

Proton Pump Inhibitors Induced Hyponatremia in a Liver Transplanted Patient—The Role of Deprescribing: A Case Report and Literature Review

Liver transplant patients are frail subjects due to lifelong therapy with immunosuppressants. In these patients, comorbidity and polytherapy increase the risk of adverse drug reactions. In this study, we report the development of hyponatremia, probably related to pantoprazole in a liver transplant patient. Sertraline dismission and treatment with sodium chloride did not improve clinical symptoms and laboratory levels. Pantoprazole dismission induced an improvement in clinical symptoms and the normalization of sodium levels. A five-month follow-up revealed the absence of clinical symptoms and normal serum sodium levels.