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1.
Cells ; 13(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38727277

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005-0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003-0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881-0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance.


Cytomegalovirus Infections , Cytomegalovirus , Enzyme-Linked Immunospot Assay , Immunocompromised Host , Interferon-gamma , Liver Transplantation , T-Lymphocytes , Humans , Liver Transplantation/adverse effects , Cytomegalovirus/immunology , Male , Female , Enzyme-Linked Immunospot Assay/methods , Middle Aged , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , T-Lymphocytes/immunology , Interferon-gamma/metabolism , Interferon-gamma/immunology , Aged , Adult , Immunosuppressive Agents/therapeutic use , Immunosuppression Therapy
2.
J Cardiothorac Surg ; 19(1): 284, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730503

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.


Counterpulsation , Hemodynamics , Liver Transplantation , Humans , Male , Middle Aged , Counterpulsation/methods , Hemodynamics/physiology , Postoperative Complications/therapy , Quality of Life , Ischemia/surgery , Ischemia/physiopathology
3.
Pediatr Transplant ; 28(4): e14599, 2024 Jun.
Article En | MEDLINE | ID: mdl-38713752

BACKGROUND: The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS: A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS: The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS: Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.


Bone Density , Liver Transplantation , Living Donors , Thoracic Vertebrae , Tomography, X-Ray Computed , Humans , Male , Female , Child , Retrospective Studies , Adolescent , Child, Preschool , Thoracic Vertebrae/surgery , Thoracic Vertebrae/diagnostic imaging , Infant , Young Adult , Treatment Outcome , Sex Factors
4.
J Infect Dev Ctries ; 18(4): 542-549, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38728648

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.


COVID-19 , Liver Transplantation , SARS-CoV-2 , Transplant Recipients , Humans , COVID-19/diagnosis , COVID-19/complications , COVID-19/epidemiology , Male , Risk Factors , Female , Middle Aged , Adult , Transplant Recipients/statistics & numerical data , Severity of Illness Index , Age Factors , Retrospective Studies , Aged , ROC Curve , Tomography, X-Ray Computed , Neutrophils
6.
Lancet Healthy Longev ; 5(5): e346-e355, 2024 May.
Article En | MEDLINE | ID: mdl-38705152

BACKGROUND: Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. METHODS: In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. FINDINGS: Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. INTERPRETATION: The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. FUNDING: None.


Liver Transplantation , Waiting Lists , Humans , Liver Transplantation/mortality , Middle Aged , Adult , United Kingdom/epidemiology , Male , Age Factors , Female , End Stage Liver Disease/surgery , End Stage Liver Disease/mortality , Aged , Algorithms , Severity of Illness Index , Transplant Recipients/statistics & numerical data
7.
BMC Med Genomics ; 17(1): 124, 2024 May 06.
Article En | MEDLINE | ID: mdl-38711024

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.


Glycogen Storage Disease Type I , Liver Neoplasms , Liver Transplantation , Humans , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/pathology , Female , Adolescent , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/complications , Adenoma/genetics , Adenoma/complications , Adenoma/pathology , Adenoma, Liver Cell/genetics , Adenoma, Liver Cell/complications , Adenoma, Liver Cell/pathology , Inflammation/genetics , Inflammation/pathology , Inflammation/complications
9.
Article En | MEDLINE | ID: mdl-38728012

A combined heart+liver transplant is the only option for survival in some patients with end-stage combined cardiac and hepatic disease. These patients may suffer from congenital or acquired cardiac disease. The potential aetiologies of the associated hepatic disease are heterogeneous and include systemic disease that impacts the liver as well as venous congestion in patients with functionally univentricular circulation. In the latter scenario, patients with functionally univentricular circulation often require complex cardiac reconstruction in the setting of a cardiac transplant after staged palliation. During cardiac procurement, our approach is to dissect the entire ascending aorta and aortic arch in continuity; the entire superior caval vein and innominate vein in continuity; and the pulmonary arteries from hilum to hilum if the donor is not a candidate for recovery of the lungs. The cardiac and abdominal organ procurement teams work in parallel during dissection and combined en bloc cardio-hepatectomy. This technique minimizes exposure of both organs to cold ischaemia. This video tutorial demonstrates the key steps for combined en bloc heart+liver organ procurement.


Heart Transplantation , Liver Transplantation , Tissue and Organ Procurement , Humans , Liver Transplantation/methods , Tissue and Organ Procurement/methods , Heart Transplantation/methods , Tissue and Organ Harvesting/methods
10.
Ugeskr Laeger ; 186(15)2024 Apr 08.
Article Da | MEDLINE | ID: mdl-38708697

Cytomegalovirus infection (CMV) can be fatal for organ transplant recipients as shown in this case report. Maribavir is a recently approved drug, which can be used for therapy-refractory CMV infection or when other treatment options cannot be used. The patient in this case report was a CMV-infected liver transplant recipient, who developed a severe erythema and high CMV DNA during valganciclovir therapy. Toxic epidermal necrolysis was suspected. The patient was treated with maribavir, and both CMV DNA and the skin normalised. This case illustrates that maribavir is a useful alternative to other antiviral drugs for CMV infection.


Antiviral Agents , Cytomegalovirus Infections , Dichlororibofuranosylbenzimidazole/analogs & derivatives , Liver Transplantation , Ribonucleosides , Humans , Cytomegalovirus Infections/drug therapy , Liver Transplantation/adverse effects , Antiviral Agents/therapeutic use , Ribonucleosides/therapeutic use , Ribonucleosides/administration & dosage , Benzimidazoles/therapeutic use , Benzimidazoles/adverse effects , Male , Middle Aged , Cytomegalovirus/isolation & purification , Cytomegalovirus/drug effects
11.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(5): 679-685, 2024 May 06.
Article Zh | MEDLINE | ID: mdl-38715509

This study aimed to investigate the differences in peripheral blood lymphocyte subsets among patients with different immune statuses in the early postoperative period after liver transplantation, as well as the dynamic changes during the early post-transplantation period. A retrospective study was conducted, selecting a total of 82 patients who underwent liver transplantation at the General Hospital of PLA Southern Theater Command from January, 2018 to December, 2023. Based on the patients' postoperative immune status, they were categorized into stable group (n=40), infection group (n=21), and rejection group (n=21). Peripheral blood samples of 2-3 ml were collected from patients at weeks 1 to 4 postoperatively, and flow cytometry was employed to measure the absolute values of peripheral blood lymphocyte subsets. For metric data conforming to normal distribution and homogeneity of variance, multiple group comparisons were conducted using ANOVA and Bonferroni multiple comparisons; for non-normally distributed data, the Kruskal Wallis test was used. Friedman test was used to compare different time periods within 4 weeks after liver transplantation. The results showed that there were no statistically significant differences in the absolute values of lymphocyte subsets among the three groups in the first week after liver transplantation (P>0.05); however, significant differences were observed in the absolute values of lymphocyte subsets among the three groups in the second, third, and fourth weeks postoperatively (P<0.05). In the second week, the rejection group showed significantly higher absolute counts of T cells, CD4+T cells, CD8+T cells, NK cells, and B cells compared to the infection group (585.0 vs. 199.0; 324.0 vs.113.0; 188.0 vs.56.0; 57.0 vs.11.0; 145.0 vs.65.0 cells/µl), with statistically significant differences (Z=-3.972, P<0.001; Z=-3.590, P=0.001; Z=-3.978, P<0.001; Z=-3.072, P=0.006; Z=-2.472, P=0.040). In the third week, the rejection group showed significantly higher absolute counts of T cells, CD4+T cells, and CD8+T cells compared to the infection group (660.0 vs.216.0; 350.0 vs.123.0; 184.0 vs.76.0 cells/µl), with statistically significant differences (Z=-3.019, P=0.008; Z=-3.492, P=0.001; Z=-2.845, P=0.013). In the fourth week, the rejection group showed significantly higher absolute counts of T cells, CD4+T cells, CD8+T cells, and B cells compared to the infection group (690.0 vs.273.0; 405.0 vs.168.0; 214.0 vs.96.0; 117.0 vs.48.0 cells/µl), with statistically significant differences (Z=-3.379, P=0.002; Z=-3.068, P=0.006; Z=-3.007, P=0.0086; Z=-2.330, P=0.020). Within 4 weeks after liver transplantation, the absolute values of T cells, CD8+T cells, and NK cells in the fourth week were higher than those in the first week, with statistically significant differences (Z=-3.825, P=0.001; Z=-3.466, P=0.003; Z=-3.526, P=0.003); however, the absolute values of B cells showed an overall decreasing trend, and were significantly lower in the fourth week than in the first and second weeks, with statistically significant differences (Z=3.705, P=0.001; Z=2.630, P=0.009). The changes in lymphocyte subset absolute values in the rejection group were more significant than those in the infection group, with T cells, CD4+T cells, and CD8+T cells showing significant increases in the second, third, and fourth weeks postoperatively compared with the first week, with statistically significant differences (Z=-3.466, P=0.003; Z=-4.661, P<0.001; Z=-5.020, P<0.001; Z=-2.749, P=0.036; Z=-4.422, P<0.001; Z=-4.542, P<0.001; Z=-3.466, P=0.003; Z=-3.765, P=0.001; Z=-4.482, P<0.001); NK cell absolute values in the third and fourth weeks postoperatively were significantly higher than those in the first week, with statistically significant differences (Z=-2.570, P=0.061; Z=-3.765, P=0.001). In summary, monitoring the differences and dynamic changes of lymphocyte subsets in patients after liver transplantation may have certain guiding significance for evaluating the immune function status of patients and adjusting treatment plans.


Liver Transplantation , Lymphocyte Subsets , Humans , Retrospective Studies , Lymphocyte Subsets/immunology , Postoperative Period , Lymphocyte Count , Male , Female , Graft Rejection/immunology
12.
Pediatr Transplant ; 28(4): e14771, 2024 Jun.
Article En | MEDLINE | ID: mdl-38702924

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.


Graft Survival , Kaplan-Meier Estimate , Liver Transplantation , Tissue Donors , Humans , Child, Preschool , Retrospective Studies , Child , Adolescent , Male , Female , Infant , Age Factors , Infant, Newborn , Proportional Hazards Models , Adult , Treatment Outcome , Living Donors
13.
J Gastrointest Surg ; 28(5): 738-745, 2024 May.
Article En | MEDLINE | ID: mdl-38704208

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.


Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Liver Transplantation , Humans , Liver Transplantation/statistics & numerical data , Male , Female , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Middle Aged , Aged , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Treatment Outcome , Neoadjuvant Therapy/statistics & numerical data , Survival Rate , Databases, Factual , Proportional Hazards Models , Kaplan-Meier Estimate , Retrospective Studies , Neoplasm Staging
14.
J Gastrointest Surg ; 28(5): 731-737, 2024 May.
Article En | MEDLINE | ID: mdl-38704207

BACKGROUND: Long-term medical and quality of life (QOL) outcomes in voluntary liver donors remain under investigated. The objective of the current study was to report long-term medical outcomes and re-evaluate QOL in living liver donors. METHODS: This was a single-center retrospective cohort study of donors who underwent donor hepatectomy between 2012 and 2018. We investigated long-term outcomes in 7 domains. These include medical problems, surgical procedures, work-related issues, pregnancy outcomes, psychiatric interventions, willingness to donate again, and long-term mortality. QOL was evaluated using short-form 36. RESULTS: The median follow-up time was 61.4 months (53.3-83.7). Among 698 donors, 80 (11.5%) experienced medical problems, 4 (0.6%) had work-related issues, and 20 (2.9%) needed psychiatric assistance. Surgery was performed in 49 donors (7%), and females were more likely to have undergone incisional hernia repair (5.8% vs 1.9%, P = .006). There were 79 postdonation pregnancies including 41 normal vaginal deliveries (51.9%), 35 cesarean sections (44.3%), and 3 miscarriages (3.8%). Willingness to donate again was reported by 658 donors (94.3%). Donors whose recipients were alive were more likely to donate again (95.5% vs 90.5%, P = .01). There were 3 deaths (0.4%) in the long-term. The mean physical composite score at initial and follow-up evaluation was 86.7 ± 13.9 and 76.5 ± 20.9 (P = .001), and the mean mental composite score at initial and follow-up evaluation was 92.1 ± 13.5 and 80.7 ± 16 (P = .001). CONCLUSION: The overall long-term outlook in living liver donors is promising. QOL parameters might deteriorate over time and frequent re-evaluation might be considered.


Hepatectomy , Liver Transplantation , Living Donors , Quality of Life , Humans , Female , Male , Retrospective Studies , Adult , Living Donors/psychology , Hepatectomy/psychology , Liver Transplantation/psychology , Middle Aged , Pregnancy , Pregnancy Outcome , Follow-Up Studies , Time Factors , Young Adult , Herniorrhaphy
15.
Hepatol Commun ; 8(5)2024 May 01.
Article En | MEDLINE | ID: mdl-38696374

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.


Continuity of Patient Care , Healthcare Disparities , Liver Diseases , Humans , Liver Diseases/therapy , Chronic Disease , Liver Transplantation , Health Equity , Health Services Accessibility , Liver Cirrhosis/therapy
16.
BMC Genomics ; 25(1): 437, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698335

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.


Gene Expression Profiling , Liver Transplantation , Liver , Tissue Donors , Humans , Liver/metabolism , Liver/pathology , Male , Middle Aged , Female , Transcriptome , Graft Rejection/genetics , Adult
17.
BMC Cancer ; 24(1): 558, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702621

BACKGROUND: Portal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear. METHODS: 110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt-TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC. RESULTS: The incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI-II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group. CONCLUSION: Compared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.


Carcinoma, Hepatocellular , Hypertension, Portal , Liver Neoplasms , Liver Transplantation , Neoplasm Recurrence, Local , Portal Vein , Humans , Liver Transplantation/adverse effects , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Male , Female , Portal Vein/pathology , Portal Vein/surgery , Middle Aged , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Case-Control Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Hypertension, Portal/surgery , Hypertension, Portal/complications , Aged , Adult
18.
Wiad Lek ; 77(3): 577-584, 2024.
Article En | MEDLINE | ID: mdl-38691803

OBJECTIVE: Aim: to review information resources and analysis of the own experience on this problem for the provision of modern knowledge in the pathogenesis of the pathology, the latest diagnostic and treatment technologies, with consideration of the need to adhere to a single strategy in the management of patients with BA. PATIENTS AND METHODS: Materials and Methods: The analysis of the data regarding the results of existing studies evaluating the clinical benefit and safety of diagnostic and treatment methods in Biliary atresia. CONCLUSION: Conclusions: BA is the leading cause of neonatal cholestasis development. Early diagnostics of BA, based on the complex evaluation of clinical-laboratory, instrumental and morphological signs of the pathology, has a significant meaning. Surgical correction during the first 2 months of life - the Kasai procedure, as well as dynamic post-surgery follow-up significantly prolong the life of children and allow postponing liver transplantation. The highest patient survival both at the first stage of treatment - conduction of the Kasai procedure and the stage of liver transplantation may be achieved by joined work of surgeons and pediatricians, which allows considering the whole row of possible problems.


Biliary Atresia , Liver Transplantation , Humans , Biliary Atresia/surgery , Biliary Atresia/diagnosis , Infant, Newborn , Infant , Child
19.
Exp Clin Transplant ; 22(3): 167-179, 2024 Mar.
Article En | MEDLINE | ID: mdl-38695585

Cholangiocarcinoma is the second most common primary hepatic neoplasm, accounting for 10% to 20% of primary liver tumors and 3% of all gastrointestinal neoplasms. The 3 anatomic types (intrahepatic, perihilar, and distal) have distinct epidemiologies, etiopathogenesis, and clinical outcomes. Surgical resection remains the current standard of treatment, but outcomes remain poor. With the continued expansion of liver transplant programs, use of liver transplant for malignant indications has also increased, with reports of encouraging outcomes. However, given the scarcity of livers fortransplant and accompanying possible complications, liver transplant for treatment of patients with cholangiocarcinomas remains experimental in most of the world. We reviewed the existing literature on treatment modalities for cholangiocarcinoma with emphasis on the pros and cons of surgical resection and indications, protocols, and outcomes of liver transplant as a treatment modality for patients with cholangiocarcinoma.


Bile Duct Neoplasms , Cholangiocarcinoma , Liver Transplantation , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/pathology , Liver Transplantation/adverse effects , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Treatment Outcome , Risk Factors , Hepatectomy/adverse effects
20.
Exp Clin Transplant ; 22(3): 223-228, 2024 Mar.
Article En | MEDLINE | ID: mdl-38695591

OBJECTIVES: Donor safety is paramount in living donor liver transplantation. However, there remains a risk of postoperative complications for some donors. Here, we provide a comprehensive assessment of donor morbidity by a single team with 17 years of experience at a single center. MATERIALS AND METHODS: We retrospectively reviewed 453 donor hepatectomies of living donor liver transplants at Kumamoto University from August 2000 to March 2017. Posterior segment graft cases were excluded in this study. RESULTS: The donors were classified by graft type as follows: right lobe (n = 173), left lobe (n = 149), and left lateral segment (n = 131). The overall complication rate was 29.8%, and the severe complication (Clavien-Dindo grade IIIa or higher) rate was 9.1%. The most frequent complication was bile leakage, with an overall incidence of 13.9% and severe incidence of 4.6%. Among the 3 types of graft, there were no significant differences in bile leakage with any Clavien-Dindo grade. However, upper gastrointestinal complications, such as a duodenal ulcer and gastric stasis, were related to left lobe donation. CONCLUSIONS: There were no significant differences in the incidence of postoperative donor complications, except upper gastrointestinal complications, among the 3 types of graft.


Hepatectomy , Liver Transplantation , Living Donors , Humans , Retrospective Studies , Liver Transplantation/adverse effects , Hepatectomy/adverse effects , Female , Male , Japan/epidemiology , Risk Factors , Treatment Outcome , Adult , Time Factors , Middle Aged , Incidence , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Young Adult , Risk Assessment
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