Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC. Methods: In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver. Results: The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02). Conclusions: This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

Simultaneous Liver Kidney Transplantation in a Primary Type 2 Hyperoxaluria With Corrected TOF and Severe Cardiomyopathy: A Case Report.

Background: Primary type 2 hyperoxaluria is a very rare genetic disorder,1,2 where in the progression to renal failure was assumed to be insidious and not very common.3 PH2 is due to deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR),1,2 which was thought to have extra-hepatic production also.4 The progression to renal failure in these patient subgroups is well documented in the Literature and the role of SLK (simultaneous liver and kidney transplantation) has not been clearly established.8. Method: We present a case report of a young girl with PH2, who successfully underwent SLK, with evidence of reduction in the urine oxalate levels post SLK. Results: PH2, though a rare genetic disease, has a proven potential to progress to chronic renal failure requiring transplantation, renal transplantation alone has not shown any benefit, these patients can be offered SLK as a primary treatment option, to improve the outcomes, this needs further validation with consensus and studies.

Differentiation and immunosuppressive function of CD19+CD24hiCD27+ regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway.

BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

Median Arcuate Ligament Syndrome (MALS) in Hepato-Pancreato-Biliary Surgery: A Narrative Review and Proposed Management Algorithm.

Median arcuate ligament syndrome (MALS) is an uncommon condition characterized by the compression of the celiac trunk by the median arcuate ligament. Due to the anatomical proximity to the foregut, MALS has significant implications in hepato-pancreato-biliary (HPB) surgery. It can pose complications in pancreatoduodenectomy and orthotopic liver transplantation, where the collateral arterial supply from the superior mesenteric artery is often disrupted. The estimated prevalence of MALS in HPB surgery is approximately 10%. Overall, there is consensus for a cautious approach to MALS when embarking on complex foregut surgery, with a low threshold for intraoperative median arcuate ligament release or hepatic artery reconstruction. The role of endovascular intervention in the management of MALS prior to HPB surgery continues to evolve, but more evidence is required to establish its efficacy. Recognizing the existing literature gap concerning optimal management in this population, we describe our tertiary center experience as a clinical algorithm to facilitate decision-making. Research question: What is the significance and management of median arcuate ligament syndrome in patients undergoing hepato-pancreato-biliary surgery?

Characterization of Perioperative Serotonin in Patients Undergoing Orthotopic Liver Transplantation.

Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff's criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.

Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

Association of Serum Levels and Immunohistochemical Labelling of Des-Gamma-Carboxy-Prothrombin in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is one of the main reasons for liver transplantation (LT). Biomarkers, such as alpha-foetoprotein (AFP) and Des-gamma-carboxy-prothrombin (DCP), can be helpful in defining the recurrence risk post LT. This study aims to evaluate the association between the intensity of DCP immunohistochemical labelling and serum DCP levels in patients undergoing LT for HCC. We carried out a prospective monocentric study including patients who all underwent LT for cirrhosis between 2016 and 2018 and all fell under the Milan criteria. The accepted diagnostic criteria for HCC were contrast-enhanced imaging and histology. Thirty-nine patients were followed for a median of 21 months, with HCC lesions categorized into negative, focally positive, and diffusely positive groups based on DCP immunohistochemistry. The serum DCP levels were significantly higher in the positive groups (258 mAU/mL for the focally and 257 mAU/mL for the diffusely positive) than in the negative group (48 mAU/mL) (p = 0.005) at diagnosis and at the time of liver transplantation (220 mAU/mL for the diffuse positive group). Microvascular invasion (58.8% vs. 19.0% for the diffusely positive and negative groups, respectively, p < 0.001) and lesion size (20 mm in the diffusely labelled group versus 12 mm in the other groups, p = 0.002) were significantly correlated with DCP labelling. Late recurrence occurred only in the positive groups; in the negative group, it occurred within the first 3 months after transplantation. DCP labelling in liver lesions correlates with serum levels and a more aggressive tumour profile. Further investigation is needed to determine if highly DCP-labelled tumours allow for the better selection of high-risk patients before LT.

Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.

Clinical characteristics of liver transplant recipients with COVID-19 and analysis of risk factors for the severe disease.

INTRODUCTION: Liver transplant (LT) recipients were at a high risk of infection during the coronavirus disease 2019 (COVID-19) pandemic. Our purpose was to compare the clinical characteristics of severe and non-severe groups of LT recipients with COVID-19, and to analyze their risk factors for severe disease. METHODOLOGY: 79 LT recipients with COVID-19 were divided into a non-severe group (n = 60) and a severe group (n = 19), and differences in clinical characteristics, laboratory tests, and chest computed tomography (CT) performance were analyzed. Logistic regression was used to identify risk factors with severe COVID-19. Receiver operating characteristic (ROC) curves were plotted and the area under curve (AUC) values were calculated to assess the predictive value for severe COVID-19. RESULTS: Age was statistically different (p < 0.001) between the two groups. The difference in neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), D-dimer, urea, C-reactive protein (CRP), lactate dehydrogenase (LDH), and the number of lung segments involved in inflammation between the two groups were statistically significant (p < 0.05). The results revealed that age (OR = 1.255, 95% CI 1.079-1.460), NLR (OR = 1.172, 95% CI 1.019-1.348), and Scr (OR = 1.041, 95% CI 1.016-1.066) were independent risk factors for severe COVID-19. The ROC results showed that high values for age, NLR and Scr predicted severe COVID-19, with AUC values of 0.775, 0.841 and 0.820, respectively, and 0.925 for the three factors combined. CONCLUSIONS: Advanced age, and elevated NLR and Scr are independent risk factors for severe COVID-19 in LT recipients.

Intraoperative hypotension during liver transplantation and postoperative outcomes: Retrospective cohort study.

STUDY OBJECTIVES: Evaluation of the association between intraoperative hypotension (IOH) and important postoperative outcomes after liver transplant such as incidence and severity of acute kidney injury (AKI), MACE and early allograft dysfunction (EAD). DESIGN: Retrospective, single institution study. SETTINGS: Operating room. PATIENTS: 1576 patients who underwent liver transplant in our institution between January 2005 and February 2022. MEASUREMENTS: IOH was measured as the time, area under the threshold (AUT), or time-weighted average (TWA) of mean arterial pressure (MAP) less than certain thresholds (55,60 and 65 mmHg). Associations between IOH exposures and AKI severity were assessed via proportional odds models. The odds ratio from the proportional odds model estimated the relative odds of having higher stage of AKI for higher exposure to IOH. Associations between exposures and MACE and EAD were assessed through logistic regression models. Potential confounding variables including patient baseline and surgical characteristics were adjusted for all models. MAIN RESULTS: The primary analysis included 1576 surgeries that met the inclusion and exclusion criteria. Of those, 1160 patients (74%) experienced AKI after liver transplant surgery, with 780 (49%), 248(16%), and 132 (8.4%) experiencing mild, moderate, and severe injury, respectively. No significant association between hypotension exposure and postoperative AKI (yes or no) nor severity of AKI was observed. The odds ratios (95% CI) of having more severe AKI were 1.02 (0.997, 1.04) for a 50-mmHg·min increase in AUT of MAP <55 mmHg (P = 0.092); 1.03 (0.98, 1.07) for a 15-min increase in time spent under MAP <55 mmHg (P = 0.27); and 1.24 (0.98, 1.57) for a 1 mmHg increase in TWA of MAP <55 mmHg (P = 0.068). The associations between IOH and the incidence of MACE or EAD were not significant. CONCLUSION: Our results did not show the association between IOH and investigated outcomes.

Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

BACKGROUND AND AIMS: Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. METHODS: In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR) ≥ 1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4 months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. RESULTS: In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p = 0.013) and delayed versus early initiation of corticosteroid (after vs. before 5 days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p = 0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (OR: 2.542; 95% CI: 1.188-5.440; p = 0.016) and delayed initiation of corticosteroids (OR: 3.578; 95% CI: 1.084-11.812; p = 0.036) were independent predictors of liver transplant free survival at 6 months after diagnosis. CONCLUSION: Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

Dominant stricture in paediatric-onset primary sclerosing cholangitis is associated with impaired prognosis in a long-term follow-up.

BACKGROUND AND OBJECTIVES: The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown. This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC. METHODS: Patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 were identified from hospital records or our PSC registry. Data including clinical, laboratory, cholangiography, and cytology at diagnosis and during follow-up (until July 2023) were reviewed. We graphed the Kaplan-Meier failure function and fitted crude and multivariable Cox model to calculate hazard ratios (HR) and 95% confidence intervals (CI) for selected variables. In these analyses, DS was treated as a time-varying variable. RESULTS: We identified 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total, 35 (51%) had concomitant autoimmune hepatitis. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing liver transplantation for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). No cholangiocarcinomas or deaths occurred during the follow-up. CONCLUSIONS: DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcome.

Financial toxicity in living donor liver transplantation: a call to action for financial neutrality.

After two decades of limited growth, LDLT has been increasingly accepted as a promising solution to the growing organ shortage in the U.S. With experience, LDLT offers superior graft and patient survival with low rates of rejection. However, not all waitlisted patients have equal access to LDLT, with financial toxicity representing a substantial barrier. Potential living liver donors face indirect, direct, and opportunity costs associated with donation as well as insurance-based discrimination and variable employer leave policies. There are multiple potential national, local, and patient-centered solutions to address some of the cost-related issues associated with living LDLT. These include standardization of employer leave policies, creation of federal and state-led tax relief programs, optimization of National Living Donor Assistance Center use, engagement of independent living donor advocates, creation of financial toolkits, and encouragement of recipient or donor-led fundraising. In this piece, members of the North American Living Liver Donation Group, a consortium of 37 LDLT programs, explore these financial challenges and discuss solutions to achieve financial neutrality, where individuals can donate free from financial constraints or gains. As a community, it is imperative that we confront factors driving financial toxicity to improve equity and access to LDLT.

Assessing hepatic steatosis by magnetic resonance in potential living liver donors.

PURPOSE: To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings. METHODS: A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner. RESULTS: Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604-0.798, r = 0.654, 95% CI: 0.544-0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 (P < 0.001, 95% CI: 0.766-0.907) and 0.810 ± 0.036 (P < 0.001, 95% CI: 0.739-0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 (P < 0.001 95% CI: 0.804-0.937) and 0.855 ± 0.036 (P < 0.001, 95% CI: 0.784-0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively. CONCLUSION: The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy.

Genome-wide DNA methylation and transcriptomic analysis of liver tissues subjected to early ischemia/reperfusion injury upon human liver transplantation.

INTRODUCTION AND OBJECTIVES: Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors. PATIENTS AND METHODS: 12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq. RESULTS: Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response. CONCLUSIONS: In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI.

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

INTRODUCTION: Post 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 PRESENTATION: A 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. CONCLUSION: We 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.

Enhanced Role of Multi-Pair Donor Swaps in Response to Size Incompatibility: The First Two 5-Way and the First 6-Way Liver Paired Exchanges.

A significant portion of liver transplantations in many countries is conducted via living-donor liver transplantation (LDLT). However, numerous potential donors are unable to donate to their intended recipients due to factors such as blood-type incompatibility or size incompatibility. Despite this, an incompatible donor for one recipient may still be a viable donor for another patient. In recent decades, several transplant centers have introduced liver paired exchange (LPE) programs, facilitating donor exchanges between patients and their incompatible donors, thereby enabling compatible transplants. Initially, LPE programs in Asia primarily involved ABO-i pairs, resulting in 2-way exchanges mainly between blood-type A and B recipients and donors. This practice has led to a modest 1-2% increase in LDLTs at some centers. Incorporating size incompatibility alongside blood-type incompatibility further enhances the efficacy and significance of multiple-pair LPEs. Launched in July 2022, a single-center LPE program established at Inönü University Liver Transplant Institute in Malatya, Türkiye, has conducted thirteen 2-way, nine 3-way, four 4-way, two 5-way, and one 6-way LPEs until February 2024. In 2023 alone, this program facilitated 64 LDLTs, constituting 27.7% of the total 231 LDLTs performed. This paper presents the world's first two 5-way LPEs and the first 6-way LPE.