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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.
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
3.
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
4.
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
5.
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
6.
Exp Clin Transplant ; 22(4): 294-299, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742320

OBJECTIVES: Bronchiectasis is characterized by abnormal, persistent, and irreversible enlargement of the bronchi. Many etiological factors have been described, but there are limited data on the development of bronchiectasis after organ transplantation. Our study is the first to study evaluate the frequency of bronchiectasis in heart and liver transplants as well as kidney transplants. Our aim is to analyze the frequency of bronchiectasis development after solid-organ transplant and the characteristics of the cases and to evaluate potential relationships. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent solid-organ transplant at the Baskent University Faculty of Medicine Hospital through the hospital electronic information system. Demographic, clinical, and laboratory data and thoracic computed tomography scans were evaluated. RESULTS: The study included 468 patients (151 females/317 males). Kidney transplant was performed in 61.5% (n = 207), heart transplant in 20.3% (n = 95), and liver transplant in 18.2% (n = 85) of patients. Development of bronchiectasis was detected in only 13 patients (2.7%). We determined a 13.64-fold risk of developing bronchiectasis in patients with chronic obstructive pulmonary disease and 10.08-fold risk in patients with pneumonia by multivariate regression analyzes, in which all possible risk factors for the development of bronchiectasis after transplant were evaluated. CONCLUSIONS: The pathophysiology of transplantassociated bronchiectasis has not yet been clarified. Underlying diseases, recurrent pulmonary infections, and potential effects from immunosuppressive drugs may contribute to the pathogenesis of bronchiectasis. Further prospective studies are needed to include long-term health outcomes in transplant patients with and without bronchiectasis.


Bronchiectasis , Heart Transplantation , Liver Transplantation , Humans , Bronchiectasis/epidemiology , Bronchiectasis/etiology , Bronchiectasis/diagnosis , Bronchiectasis/diagnostic imaging , Retrospective Studies , Male , Female , Risk Factors , Middle Aged , Adult , Treatment Outcome , Liver Transplantation/adverse effects , Turkey/epidemiology , Heart Transplantation/adverse effects , Kidney Transplantation/adverse effects , Time Factors , Risk Assessment , Aged , Organ Transplantation/adverse effects , Young Adult , Hospitals, University , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology
7.
Exp Clin Transplant ; 22(4): 311-313, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742323

Biliary strictures afterlivertransplant are amenable to endoscopic dilatation or percutaneous dilatation and stenting in most cases. In rare cases, for recurrence or tight stricture, surgery is required, and hepaticojejunostomy is the favored procedure. We report a case of posttransplant stricture in a duct-to-duct anastomosis that could not be accessed due to prior gastric bypass. Despite multiple percutaneous transhepatic cholangiography dilatations, the stricture recurred, and the patient was taken up for bilioenteric bypass. During surgery, dense adhesions in the infracolic compartment with chronically twisted jejunal loops, due to prior mini gastric bypass, were encountered, which prevented the creation of a jejunal Roux limb. Hepaticoduodenostomy was performed with no recurrence of stricture at 12 months. Hepaticoduodenostomy is a viable option for surgical management of recurrent biliary strictures, especially in a setting of prior bariatric/diversion procedures.


Duodenostomy , Liver Transplantation , Recurrence , Reoperation , Humans , Liver Transplantation/adverse effects , Constriction, Pathologic , Treatment Outcome , Cholestasis/etiology , Cholestasis/surgery , Cholestasis/diagnostic imaging , Middle Aged , Anastomosis, Surgical , Female , Male , Cholangiography
8.
Exp Clin Transplant ; 22(4): 284-293, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742319

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.


Blood Coagulation , Blood Platelets , End Stage Liver Disease , Liver Transplantation , Predictive Value of Tests , Splenectomy , Thrombelastography , Humans , Liver Transplantation/adverse effects , Male , Female , Middle Aged , Splenectomy/adverse effects , Treatment Outcome , Blood Coagulation/drug effects , Adult , End Stage Liver Disease/surgery , End Stage Liver Disease/diagnosis , End Stage Liver Disease/blood , Time Factors , Blood Platelets/drug effects , Platelet Activation/drug effects , Platelet Function Tests , Platelet Aggregation Inhibitors/administration & dosage , Anticoagulants/administration & dosage , Platelet Count , Blood Coagulation Tests , Aspirin/administration & dosage , Prospective Studies
9.
Exp Clin Transplant ; 22(4): 318-321, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742325

Tigecycline is a parenteral glycycline antibiotic that is used to treat severe infections caused by susceptible organisms, butitis also associated with hepatotoxicity. We present 2 similar patients with hepatic steatosis possibly associated with early tigecycline after transplant. In the first case, a 61-year-old woman underwent liver transplant for acute severe hepatitis; 6 days posttransplant, because of nonroutine resistant fever, the patient received tigecycline combined with daptomycin. Retransplant was applied to the patient on day 12 posttransplant because of acute liver failure secondary to hepatic vein thrombosis. After retransplant, biochemical levels gradually increased, exceeding the upper limit of normal. In liver biopsy, the patient had macrovesicular steatosis in 70% to 80% ofthe parenchyma. In the second case, a 53-yearold woman underwent liver transplant for liver cirrhosis. Tigecycline was added to the treatment because of recurrent fever on day 6 after transplant, with treatment also comprising piperacillin-tazobactam and meropenem. On day 15 of the patient's tigecycline treatment, her liver function tests were elevated. In liver biopsy, the patient had 30% to 40% macrovesicular steatosis and canalicular cholestasis in the parenchyma, especially in zone 3. Reports of hepatic steatosis associated with early tigecycline after transplant are quite new to the literature.


Anti-Bacterial Agents , Fatty Liver , Liver Transplantation , Tigecycline , Humans , Tigecycline/adverse effects , Female , Middle Aged , Liver Transplantation/adverse effects , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Fatty Liver/chemically induced , Fatty Liver/diagnosis , Treatment Outcome , Biopsy , Minocycline/adverse effects
10.
Exp Clin Transplant ; 22(4): 314-317, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742324

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.


Antifungal Agents , Immunocompromised Host , Liver Cirrhosis, Biliary , Liver Transplantation , Mucormycosis , Humans , Male , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/immunology , Mucormycosis/drug therapy , Mucormycosis/etiology , Middle Aged , Liver Transplantation/adverse effects , Antifungal Agents/therapeutic use , Fatal Outcome , Liver Cirrhosis, Biliary/surgery , Liver Cirrhosis, Biliary/microbiology , Liver Cirrhosis, Biliary/diagnosis , Treatment Outcome , Opportunistic Infections/microbiology , Opportunistic Infections/immunology , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Debridement , Allografts , Hepatectomy , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Multiple Organ Failure/etiology , Multiple Organ Failure/microbiology
11.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38731866

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.


Fatty Liver , Liver Transplantation , Organ Preservation , Reperfusion Injury , Tissue Donors , Humans , Reperfusion Injury/prevention & control , Liver Transplantation/methods , Liver Transplantation/adverse effects , Organ Preservation/methods , Fatty Liver/pathology , Liver/pathology , Organ Preservation Solutions , Animals , Perfusion/methods
12.
Medicina (Kaunas) ; 60(4)2024 Apr 18.
Article En | MEDLINE | ID: mdl-38674295

Background and Objectives: The aim of this study is to evaluate the clinical and laboratory changes of ischemia and reperfusion injury in the remnant livers of donors with and without Pringle maneuver. Furthermore, we evaluated the recipients who have been transplanted with liver grafts from these donors. Methods and Materials: A total of 108 patients (54 living liver donors and 54 liver recipients) who underwent donor hepatectomy and recipients who living donor liver transplantation, were included in this randomized double-blind study between February 2021 and June 2021. The donors were divided into two groups: Pringle maneuver applied (n = 27) and Pringle maneuver not applied (n = 27). Similarly, recipients with implanted liver obtained from these donors were divided into two groups as the Pringle maneuver was performed (n = 27) and not performed (n = 27). Blood samples from donors and recipients were obtained on pre-operative, post-operative 0 h day (day of surgery), post-operative 1st day, post-operative 2nd day, post-operative 3rd day, post-operative 4th day, post-operative 5th day, and liver tissue was taken from the graft during the back table procedures. Liver function tests and complete blood count, coagulation tests, IL-1, IL-2, IL-6, TNF-α, and ß-galactosidase measurements, and histopathological findings were examined. Results: There was no statistically significant difference in the parameters of biochemical analyses for ischemia-reperfusion injury at all periods in the donors with and without the Pringle maneuver. Similarly, there was no statistically significant difference between in the recipients in who received liver grafts harvested with and without the Pringle maneuver. There was no statistically significant difference between the two recipient groups in terms of perioperative bleeding and early bile duct complications (p = 0.685). In the histopathological examinations, hepatocyte damage was significantly higher in the Pringle maneuver group (p = 0.001). Conclusions: Although the histological scoring of hepatocyte damage was found to be higher in the Pringle maneuver group, the Pringle maneuver did not augment ischemia-reperfusion injury in donors and recipients that was evaluated by clinical and laboratory analyses.


Hepatectomy , Liver Transplantation , Living Donors , Reperfusion Injury , Humans , Reperfusion Injury/etiology , Male , Hepatectomy/methods , Hepatectomy/adverse effects , Female , Middle Aged , Liver Transplantation/methods , Liver Transplantation/adverse effects , Adult , Double-Blind Method , Liver/blood supply , Liver/injuries , Liver/surgery
13.
World J Gastroenterol ; 30(14): 1958-1962, 2024 Apr 14.
Article En | MEDLINE | ID: mdl-38681123

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.


End Stage Liver Disease , HIV Infections , Liver Transplantation , Humans , HIV Infections/epidemiology , HIV Infections/complications , HIV Infections/diagnosis , Liver Transplantation/adverse effects , Liver Transplantation/methods , China/epidemiology , End Stage Liver Disease/surgery , End Stage Liver Disease/mortality , End Stage Liver Disease/diagnosis , End Stage Liver Disease/virology , Treatment Outcome , Prevalence , Coinfection , Antiretroviral Therapy, Highly Active , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis B/diagnosis , Hepatitis B/complications
14.
Sci Adv ; 10(15): eadm8841, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608023

Allograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell-mediated rejection (TCMR), or chronic rejection (CR). This approach generated a spatially resolved proteomic atlas of 461,816 cells (42 phenotypes) derived from 96 pathologist-selected regions of interest. Our analysis revealed that regulatory (HLADR+ Treg) and PD1+ T cell phenotypes (CD4+ and CD8+ subsets), combined with variations in M2 macrophage polarization, were a unique signature of active TCMR. These data provide insights into the alloimmune microenvironment in clinical LT, including identification of potential targets for focused immunotherapy during rejection episodes and suggestion of a substantial role for immune exhaustion in TCMR.


Immune System Exhaustion , Liver Transplantation , Liver Transplantation/adverse effects , Proteomics , Biopsy , Immunotherapy
15.
World J Gastroenterol ; 30(11): 1488-1493, 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38617447

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation. Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses, providing the highest available evidence on the protective effect of machine perfusion (MP) over static cold storage in liver transplantation (LT). Based on a protective effect with less complications and improved graft survival, the field has seen a paradigm shift in organ preservation. This editorial focuses on the role of MP in LT and how it could become the new "gold standard". Strong collaborative efforts are needed to explore its effects on long-term outcomes.


Liver Transplantation , Perfusion , Humans , Blood Coagulation Tests , Cryopreservation , Graft Survival , Liver Transplantation/adverse effects
16.
Am J Case Rep ; 25: e943042, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38627956

BACKGROUND A paradoxical air embolism (PAE) occurs when air entering the central venous circulation reaches the systemic circulation, occurring through an intracardiac shunt or intrapulmonary shunting. Patients presenting for liver transplantation often have intrapulmonary shunting due to pulmonary arterial vasodilation, even in the absence of hepatopulmonary syndrome. Here, we present a case of hemodynamic collapse believed to be caused by a PAE, which was diagnosed intraoperatively with transesophageal echocardiography (TEE). CASE REPORT A 60-year-old man who was diagnosed with non-alcoholic steatohepatitis cirrhosis presented for deceased donor orthotopic liver transplantation with utilization of normothermic machine perfusion. Following reperfusion of the liver allograft, TEE detected intrapulmonary shunting resulting in air within the left atrium, left ventricle, and ascending aorta. The patient developed severe biventricular dysfunction with ST-segment changes on electrocardiography monitoring and became acutely hypotensive with significant hepatic congestion 5 min after liver reperfusion. High doses of inotropic and vasopressor support were used as well as inhaled nitric oxide. The patient recovered after 30 min of medical management. The liver transplantation operation was successfully completed and the patient was discharged home on postoperative day 7. CONCLUSIONS Intracardiac air at the time of reperfusion during liver transplantation can originate from the donor allograft and result in PAE in the setting of intrapulmonary shunting. PAE can result in intracoronary air and should be considered in cases of hemodynamic instability in liver transplantation, especially if air is seen within the left atrium, left ventricle, and ascending aorta.


Embolism, Air , Liver Transplantation , Male , Humans , Middle Aged , Liver Transplantation/adverse effects , Embolism, Air/etiology , Liver Cirrhosis/complications , Echocardiography, Transesophageal
17.
Sci Rep ; 14(1): 7828, 2024 04 03.
Article En | MEDLINE | ID: mdl-38570629

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).


Hyperthyroidism , Hypothyroidism , Liver Transplantation , Female , Humans , Hyperthyroidism/epidemiology , Hyperthyroidism/complications , Hypothyroidism/etiology , Hypothyroidism/complications , Liver Transplantation/adverse effects , Prevalence , Risk Factors , Thyrotropin , Male , Adult
18.
Hepatobiliary Pancreat Dis Int ; 23(2): 117-122, 2024 Apr.
Article En | MEDLINE | ID: mdl-38619051

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.


Liver Neoplasms , Liver Transplantation , Humans , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Consensus
19.
Pediatr Transplant ; 28(3): e14727, 2024 May.
Article En | MEDLINE | ID: mdl-38613151

BACKGROUND: Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence. METHODS: Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures. RESULTS: Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3-215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses. CONCLUSIONS: In our cohort, the presence of two biliary anastomoses and post-transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.


Liver Transplantation , Male , Humans , Child , Child, Preschool , Female , Liver Transplantation/adverse effects , Constriction, Pathologic/epidemiology , Constriction, Pathologic/etiology , Constriction, Pathologic/therapy , Incidence , Risk Factors , Referral and Consultation
20.
Pediatr Transplant ; 28(3): e14749, 2024 May.
Article En | MEDLINE | ID: mdl-38623878

AIM: Acquired post-transplant diaphragmatic hernia (PTDH) is a rare complication of liver transplantation (LT) in children. We aimed to present our experience in PTDH, and a possible causative background is discussed. METHODS: Medical records of patients who had undergone diaphragmatic repair following LT between 2015 and 2023 were reviewed. Demographic information, details of primary diseases necessitating LT, transplantation techniques, and clinical findings associated with PTDH were evaluated. RESULTS: There were seven patients with PTDH. Median age at transplantation was 69 (range: 9-200) months. Five patients received a left lateral sector, one patient had a right lobe, and one had a left lobe graft. Time between LT and PTDH was 9 (2-123) months. One patient who was diagnosed in the postoperative 10th year was asymptomatic. Respiratory distress and abdominal pain were the main symptoms among all. All patients underwent laparotomy, and primary repair was performed in six patients, and one patient required mesh repair because of a large defect. Small intestine herniated in most cases. There were two complicated cases with perforation of the stomach and colonic volvulus. There is no recurrence or long-term complications for the median 60 (20-119) month follow-up period. CONCLUSION: PTDH is a rare but serious complication. Majority of symptomatic cases present within the first postoperative year, whereas some late-presenting cases may not be symptomatic. Inadvertent injury to the inferior phrenic vasculatures due to excessive use of cauterization for control of hemostasis may be a plausible explanation in those cases.


Hernia, Diaphragmatic , Intestinal Volvulus , Liver Transplantation , Humans , Child , Liver Transplantation/adverse effects , Hernia, Diaphragmatic/surgery , Hernia, Diaphragmatic/complications , Tomography, X-Ray Computed/adverse effects , Abdominal Pain/complications
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