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.

Bronchiectasis After Solid-Organ Transplant: A Retrospective Single Center Study.

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.

Hepaticoduodenostomy for Recurrent Biliary Anastomotic Stricture after Liver Transplant.

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.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

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.

Tigecycline-Associated Hepatic Steatosis After Liver Transplant: A Case Report.

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.

Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

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.

Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Solid Organ Transplant Litigation at One of Europe's Largest University Hospitals.

Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase in litigation related to medical activity. Litigation relating to solid organ transplantation that took place in the 29 units of the Assistance Publique-Hôpitaux de Paris and was the subject of a judicial decision between 2015 and 2022 was studied. A total of 52 cases of SOT were recorded, all in adults, representing 1.1% of all cases and increasing from 0.71% to 1.5% over 7 years. The organs transplanted were 25 kidneys (48%), 19 livers (37%), 5 hearts (9%) and 3 lungs (6%). For kidney transplants, 11 complaints (44%) were related to living donor procedures and 6 to donors. The main causes of complaints were early post-operative complications in 31 cases (60%) and late complications in 13 cases (25%). The verdicts were in favour of the institution in 41 cases (79%). Solid organ transplants are increasingly the subject of litigation. Although the medical institution was not held liable in almost 80% of cases, this study makes a strong case for patients, living donors and their relatives to be better informed about SOT.

Maribavir for treatment of cytomegalovirus infection in a liver-transplanted patient.

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.

Current State of Liver Transplantation for Cholangiocarcinoma: A Comprehensive Literature Review.

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.

Donor Complications Following Living Donor Hepatectomy: 17-Year Experience of a Single Team in One Institution of Japan.

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.

Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study.

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.

Asystolic donor warm ischemia time is associated with development of postreperfusion syndrome in donation after circulatory death liver transplant.

BACKGROUND: Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes. METHODS: This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure < 80 mmHg; oxygen saturation < 80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression. RESULTS: The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p = .02; 5.2 mg/dL vs. 3.4 mg/dL), POD 3 (p = .049; 4.5 mg/dL vs. 2.8 mg/dL), and POD 7 (p = .04; 3.1 mg/dL vs. 1.9 mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p = .01; 48.2% vs. 23.1%). CONCLUSION: Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.

Immunomonitoring via ELISPOT Assay Reveals Attenuated T-Cell Immunity to CMV in Immunocompromised Liver-Transplant Patients.

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.

Oral candidiasis in liver transplant patients: species identification and antifungal susceptibility profile.

OBJECTIVE: This study aimed to verify oral candidiasis, identify the causative species, and investigate the antifungal susceptibility of yeasts isolated from liver transplant patients. METHODS: A descriptive analysis of 97 patients who underwent liver transplantation was conducted at a hospital. Two clinical examinations (Collections A and B) of the oral cavity were performed. Oral material was collected from all patients, inoculated in Sabouraud Dextrose Agar, and incubated at 35℃ for 48 hours. Samples were identified by molecular sequencing of the internal trascribed space region of rDNA. RESULTS: An antifungal susceptibility test with fluconazole, amphotericin B, and micafungin was performed using the Clinical and Laboratory Standards Institute yeast broth microdilution method. Among the patients, 15 presented with oral candidiasis: eight in Collection A and seven in Collection B. The primary type of candidiasis was atrophic, followed by pseudomembranous candidiasis. The most prevalent species was Candida albicans (nine), followed by Candida glabrata (three), Candida tropicalis (two), and Candida dubliniensis (one). Regarding susceptibility to fluconazole, of the 15 samples, 11 were susceptible, three were susceptible in a dose-dependent manner, and one was resistant. CONCLUSION: The most commonly identified type of candidiasis was atrophic, with C. albicans and C. glabrata being the most prevalent causative species. One fluconazole-resistant isolate each of C. tropicalis and C. albicans were identified.

A new method to predict venous complications in pediatric liver transplantation: Evaluation of splenic parameters by ultrasonography.

BACKGROUND: Venous complications after pediatric liver transplantation seriously affect the survival rate of patients and grafts. At present, the diagnostic indicators have not been unified. Venous complications may cause portal hypertension, which may lead to splenomegaly and splenic vein dilatation. Therefore, the changes in spleen may be closely related to the venous complications. The purpose of this study was to explore the relationship between ultrasonic splenic parameters and venous complications and to study whether these splenic parameters can be used for the diagnosis of venous complications. METHODS: We retrospectively included pediatric patients who underwent liver transplantation and collected ultrasonic spleen parameters before, and then 1-3 days, 1-3 weeks, 1-3 months, and 4-12 months after liver transplantation. We observed whether there were portal vein or hepatic vein complications within 1 year after liver transplantation. RESULTS: Among 109 pediatric patients after liver transplantation included in our study, 11 of them suffered from portal vein complications and nine hepatic vein complications. Spleen transverse diameter, spleen longitudinal diameter, spleen portal vein diameter, spleen index, spleen transverse diameter ratio, spleen longitudinal diameter ratio, and spleen index ratio were independent risk factors of venous complications. The accuracy of spleen transverse diameter (AUROC: 0.73), spleen index (AUROC: 0.70), spleen transverse diameter ratio (AUROC: 0.71), and spleen index ratio (AUROC: 0.72) in predicting venous complications were higher than other ones. CONCLUSIONS: Ultrasonic examination is a common follow-up method for pediatric patients after liver transplantation and the application of ultrasonic spleen parameters may be helpful to monitor venous complications.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

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.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

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).

Biliary strictures post pediatric liver transplantation-incidence and risk factors in a single tertiary referral transplant center.

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.