Liver Transplant Recipients Research Articles

A Tailored Virtual Program for Alcohol Use Disorder Treatment Among Liver Transplant Candidates and Recipients Is Feasible and Associated With Lower Post-Transplant Relapse.

Alcohol-associated liver disease (ALD) is a leading indication for liver transplant (LT) in the United States. Rates of early liver transplant (ELT) with less than 6 months of sobriety have increased substantially. Patients who receive ELT commonly have alcohol-associated hepatitis (AH) and are often too ill to complete an intensive outpatient program (IOP) for alcohol use disorder (AUD) prior to LT. ELT recipients feel alienated from traditional IOPs. We implemented Total Recovery-LT, a tailored virtual outpatient IOP specific for patients under evaluation or waitlisted for LT who were too ill to attend community-based alcohol treatment programs. The 12-week program consisted of weekly group and individual counseling delivered by a master's level Certified Addiction Counselor trained in the basics of LT.Treatment consisted of 12-Step Facilitation, Motivational Interviewing, and Cognitive Behavioral Therapy. We report on program design, implementation, feasibility and early outcomes. From March 2021 to September 2022, 42 patients (36% female, 23 in LT evaluation, 19 post-transplant) enrolled across five cohorts with 76% (32/42) completing the program. Alcohol relapse was more common among noncompleters versus those who completed the program (8/10, 80%vs. 7/32, 22%, p = 0.002). History of trauma or post-traumatic stress symptoms were associated with lower likelihood of completion. Patients' desire for continued engagement after completion led to the creation of a monthly alumni group. Our integrated IOP model for patients with high-risk AUD in LT evaluation or post-transplant is well-received by patients and could be considered a model for LT programs.

Carbapenem-Resistant Enterobacteriaceae Colonization or Infection Was Not Associated with Post-Liver Transplant Graft Failure: An Observational Cohort Study

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) epidemiology among liver transplant (LT) recipients is variable. We studied the impact of CRE colonization and infection on LT recipients’ outcomes. Methods: This observational cohort study included consecutive adult LT recipients between January 2019 and December 2020 at Curry Cabral Hospital, Lisbon, Portugal. Primary exposures were CRE colonization (rectal swabs under a screening program) and infection within 1 year of index LT. Primary endpoint was graft failure within 1 year of the index LT. Results: Among 209 patients, the median (interquartile range [IQR]) age was 57 (47–64) years and 155 (74.2%) were male. CRE colonization was identified in 28 (13.4%) patients during the first year posttransplant (median [IQR] number of rectal swabs per patient of 4 [2–7]). CRE resistance genes identified were OXA48 in 8 (3.6%) patients, KPC in 19 (67.9%) patients, and VIM in 1 (3.6%) patient. Any bacterial/fungal and CRE infections were diagnosed in 88 (42.1%) and 6 (2.9%) patients, respectively, during the first year posttransplant. After adjusting for confounders, neither CRE colonization (aOR [95% CI] = 1.83 [0.71–4.70]; p = 0.21) nor infection (aOR [95% CI] = 1.35 [0.17–11.06]; p = 0.78) was associated with graft failure within 1 year of index LT. Discussion/Conclusion: Under a screening program, CRE colonization and infection prevalence was low and neither was associated with graft failure.

Detecting drug-resistant human cytomegalovirus mutations in liver transplant recipients: A study of the UL97 gene

Human cytomegalovirus (HCMV or HHV-5) is a member of the beta herpesvirus family and remains dormant for life after the initial infection. However, if conditions such as immunosuppression occur, the virus can become active again and lead to severe diseases. The incidence of disease in solid organ transplant (SOT) recipients is reduced by prophylactic use of ganciclovir (either intravenously or orally). This study aimed to determine the pattern of clinical mutations associated with the cytomegalovirus UL97 gene after treatment with ganciclovir and the effect of these mutations on disease progression in liver transplant recipients infected with Iranian HCMV strains. Six HCMV-positive liver transplant recipients were enrolled, comprising 3 (50.0 %) males and 3 (50.0 %) females. Sequence analysis and mutation detection were performed using Finch software (version 1.4.0) and the NCBI Nucleotide Blast database, whereas phylogenetic analysis was performed using MEGA X (version 10.0.5). Mann-Whitney U nonparametric test, Chi-square test, Spearman's correlation coefficient analysis, were employed for statistical analysis. The results of the study showed that two samples from two patients had mutations in the UL97 gene, and the viral load of the mutated samples decreased after administering antiviral medications. Furthermore, the phylogenetic tree demonstrated a close relationship between the Iranian HCMV strains and global reference sequences.

Baseline Lung Allograft Dysfunction After Bilateral Lung Transplantation Is Associated With an Increased Risk of Death: Results From a Multicenter Cohort Study.

A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level. This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart. BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; P = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; P = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; P = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; P = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log10(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: -0.0095 [0.0007] versus -0.0109 [0.0007]; P = 0.15). BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.

Lung Donation and Transplant Recipient Outcomes at Independent vs Hospital-Based Donor Care Units

Centralizing deceased organ donor management and organ recovery into donor care units (DCUs) may mitigate the critical organ shortage by positively impacting donation and recipient outcomes. To compare donation and lung transplant outcomes between 2 common DCU models: independent (outside of acute-care hospitals) and hospital-based. This is a retrospective cohort study of Organ Procurement and Transplantation Network deceased donor registry and lung transplant recipient files from 21 US donor service areas with an operating DCU. Characteristics and lung donation rates among deceased donors cared for in independent vs hospital-based DCUs were compared. Eligible participants included deceased organ donors (aged 16 years and older) after brain death, who underwent organ recovery procedures between April 26, 2017, and June 30, 2022, and patients who received lung transplants from those donors. Data analysis was conducted from May 2023 to March 2024. Organ recovery in an independent DCU (vs hospital-based DCU). The primary outcome was duration of transplanted lung survival (through December 31, 2023) among recipients of lung(s) transplanted from cohort donors. A Cox proportional hazards model stratified by transplant year and program, adjusting for donor and recipient characteristics was used to compare graft survival. Of 10 856 donors in the starting sample (mean [SD] age, 42.8 [15.2] years; 6625 male [61.0%] and 4231 female [39.0%]), 5149 (primary comparison group) underwent recovery procedures in DCUs including 1466 (28.4%) in 11 hospital-based DCUs and 3683 (71.5%) in 10 independent DCUs. Unadjusted lung donation rates were higher in DCUs than local hospitals, but lower in hospital-based vs independent DCUs (418 donors [28.5%] vs 1233 donors [33.5%]; P < .001). Among 1657 transplant recipients, 1250 (74.5%) received lung(s) from independent DCUs. Median (range) duration of follow-up after transplant was 734 (0-2292) days. Grafts recovered from independent DCUs had shorter restricted mean (SE) survival times than grafts from hospital-based DCUs (1548 [27] days vs 1665 [50] days; P = .04). After adjustment, graft failure remained higher among lungs recovered from independent DCUs than hospital-based DCUs (hazard ratio, 1.85; 95% CI, 1.28-2.65). In this retrospective analysis of national donor and transplant recipient data, although lung donation rates were higher from deceased organ donors after brain death cared for in independent DCUs, lungs recovered from donors in hospital-based DCUs survived longer. These findings suggest that further work is necessary to understand which factors (eg, donor transfer, management, or lung evaluation and acceptance practices) differ between DCU models and may contribute to these differences.

Effects of Hepatic Artery Type And Number on Bile Complications in Right Lobe Living Donor Liver Transplant Recipients: Single Center Experience Without Hepatic Artery Thrombosis

Purpose: Hepatic artery provides blood supply to the biliary tract of the graft, one of the causes of the biliary complications that may occur in the post-transplant period may be the problems of the recipient's hepatic artery. We examined the effect of post-transplant biliary complications according to the type and number of recipient hepatic artery. Materials and Methods: One hundred eighty five patients older than 18 years of age who underwent right lobe LDLT for end-stage liver cirrhosis were included in the study. The recipient's right hepatic artery (RHA), left hepatic artery (LHA), propria hepatic artery (PHA) and common hepatic artery (CHA), which were anastomosed to the graft artery and double hepatic artery anastomoses formed of the right and left hepatic arteries, were examined. Biliary complications were analyzed statistically in terms of single or double artery anastomosis and anastomoses with the right or the other hepatic arteries. Results: There was no statistically significant difference between single and dual artery anastomoses in terms of bile duct stricture or leakage (p=0.767). No statistically significant difference was observed between RHA, LHA, PHA, CHA, and between single and dual arteries in the evaluation of artery selection between those with and without biliary tract complications (p=0.445) Conclusion: Hepatic artery type selection and number of the recipient does not change the biliary tract complication.

Single-center experience of intraoperative ligation of the splenic artery for prevention of splenic artery steal syndrome in patients after living donor liver transplant

Background. Living donor liver transplant is an effective method of treatment in patients with different types of endstage liver diseases. Unfortunately, patients undergoing such a complex treatment sometimes develop various vascular complications. Splenic artery steal syndrome has emerged as a cause of graft ischemia in living donor liver transplant recipients and may lead to high liver enzyme levels, cholestasis, hepatic artery thrombosis, and even a graft loss in some severe cases.Objective. Evaluation of the first results in the experience of our center with a routine intraoperative ligation of the splenic artery during the procedure of right lobe living donor liver transplantation in adult recipients for the prevention of the steal syndrome development in the postoperative period.Material and methods. Living donor liver transplant recipients with known hepatic arterial flow impairment were retrospectively studied. Patients were allocated into groups with regard whether the splenic artery had been ligated or not during the transplant procedure. Arterial complications were reviewed in both groups.Results. None of 30 patients with ligated splenic artery developed splenic artery steal syndrome after living donor liver transplant. splenic artery steal syndrome occurred in 60% patients with non-ligated splenic artery. Surgical technique of performing arterial anastomosis was not related to the splenic artery steal syndrome development (p&lt;0.01 There was no local ischemic necrosis noted in the spleen in patients with the ligated splenic artery.Conclusion. Based on the analysis of our own experience and literature data, the splenic artery ligation appears to be an effective and safe method for preventing a splenic artery steal syndrome in patients following right lobe liver transplantation, with a minimal risk of ischemic complications for the spleen. However, further studies with larger sample sizes are needed to obtain more reliable results. Ultrasound examination and endovascular intervention are the primary tools for an early detection of abnormalities and rapid restoration of arterial blood flow in the hepatic artery of the graft.

Pneumonia promotes pulmonary metastasis of HCC after transplantation via VEGF regulated PI3K/AKT/Cas-9 signaling and angiogenesis

Aim: Pneumonia is the most frequent early postoperative complication in liver transplantation (LT) recipients. Inflammation may provide a favorable environment for tumor implantation, so we aimed to evaluate the impact of pneumonia on pulmonary metastasis of hepatocellular carcinoma (HCC) and reveal its underlying mechanism. Methods: A training cohort with 234 LT recipients were recorded and analyzed. Using the propensity-score method, we matched covariates between patients with and without pneumonia. A model for predicting pulmonary metastasis was built and validated in an independent validating cohort containing 179 subjects. A mouse model was built to mimic HCC pulmonary metastasis. The potential pathway was revealed by cytokine array analysis and validated in vitro . Results: Pneumonia was an independent risk factor for pulmonary metastasis in liver transplant recipients. It promoted pulmonary metastasis in both the clinical setting and the mouse model. In vitro , LPS-stimulated VEGF secretion from macrophages in the lung significantly reduced cell apoptosis and activated PI3K/AKT/cas-9 signaling. Administration of VEGF receptor2 inhibitor Vatalanib could reduce metastasis and improve prognosis in pneumonia mice. Conclusion: Pneumonia promotes HCC pulmonary metastasis by activating PI3K/AKT/Cas-9 signaling in HCC cells via macrophage-originated VEGF. Vatalanib might be efficient in reducing HCC pulmonary metastasis in liver transplant recipients with pneumonia.

Constructing an Intent-to-Treat Score Index to Predict Survival Outcomes in Pediatric Liver Transplant Recipients.

Waitlist and posttransplant outcomes have been widely reported for pediatric liver transplantation. Yet, analyzing these metrics individually fails to provide a holistic perspective for patients and their families. Intent-to-treat (ITT) analysis fills this gap by studying the associations between waitlist outcomes, organ availability, and posttransplant outcomes. Our study aimed to construct a predictive index utilizing ITT analysis for pediatric liver transplant recipients (Pedi-ITT). We performed a retrospective analysis utilizing de-identified data provided by the United Network for Organ Sharing (UNOS) from March 1, 2002, to December 31, 2021. We analyzed data for 12 926 pediatric recipients (age <18). We conducted a univariate and multivariable logistic regression to find the significant predictive factors affecting ITT survival. A scoring index was constructed to stratify outcome risk on the basis of the significant factors identified by regression analysis. Multivariable analysis found the following factors to be significantly associated with death on the waitlist or after transplant: gender, diagnosis, UNOS region, ascites, diabetes mellitus, age at the time of listing, serum sodium at the time of listing, total bilirubin at the time of listing, serum creatinine at the time of listing, INR at the time of listing, history of ventilator use, and history of re-transplantation. Using receiver operator characteristic analysis, the Pedi-ITT index had a c-statistic of 0.79 (95% confidence interval [CI]: 0.76-0.82). The c-statistics of the Model for End-Stage Liver Disease/Pediatric for End-Stage Liver Disease and pediatric version of the Survival Outcomes Following Liver Transplantation score indices were 0.74 (CI: 0.71-0.76) and 0.69 (CI: 0.66-0.72), respectively. The Pedi-ITT index provides an additional prognostic model with moderate predictive power to assess outcomes associated with pediatric liver transplantation. Further analysis should focus on increasing the predictive power of the index.

Association of Preoperative Red Cell Distribution Width with Postoperative Outcomes in Liver Transplantation Recipients

Background: The 1-year mortality rate after liver transplantation is approximately 8%-20%. It is important to explore risk factors associated with postoperative outcomes in liver transplantation recipients (LTRs). Red cell distribution width (RDW) is an indicator that assesses the variability in the volume of red blood cells in circulation. RDW is not only related to inflammatory levels and nutritional status but also associated with postoperative outcomes in surgical patients. However, the relationship between preoperative RDW and postoperative outcomes in LTRs remains unclear. Therefore, we designed a retrospective observational study to investigate the impact of preoperative RDW levels on postoperative outcomes in LTRs. Methods: We retrospectively collected clinical data of patients who underwent allogeneic liver transplantation at West China Hospital, Sichuan University, from January 2016 to December 2020. The primary outcome was 1-year mortality. Secondary outcomes included 30-day mortality, long-term survival, early postoperative graft dysfunction, acute kidney injury, renal replacement therapy, pulmonary complications, duration of postoperative mechanical ventilation, length of ICU stay, and length of hospital stay. Patients were divided into two groups: RDW ≤ 14.5% and RDW &gt; 14.5%. We selected 14 covariates and used propensity score matching (PSM) to adjust for baseline characteristics. Postoperative outcomes and long-term survival were analyzed after PSM. Receiver operating characteristics (ROC) curves and subgroup analyses were also performed. Results: A total of 661 patients who underwent liver transplantation surgery were screened for this study. Finally, 438 patients were included in the statistical analysis. After PSM, there were no statistically significant differences in postoperative mortality and complications between the RDW ≤ 14.5% group and the RDW &gt; 14.5% group (P &gt; 0.05). The comparison of long-term survival between the two groups also showed no statistical difference (hazard ratio = 0.67, 95% confidence interval: 0.28-1.61, P = 0.358). Subgroup analyses showed consistent results. The ROC curve indicated that the predictive ability of preoperative RDW levels for 1-year mortality is moderate (area under the ROC curve 0.661). Conclusion: Preoperative RDW levels do not affect postoperative mortality and the incidence of complications in LTRs. However, these results still need further research for verification.

Donor to recipient age matching in lung transplantation: A European experience

BackgroundThe age profile of organ donors and patients on lung transplantation (LT) waiting lists have changed over time. In Europe, the donor population has aged much more rapidly than the recipient population, making allocation decisions on lungs from older donors common. In this study we assessed the impact of donor and recipient age discrepancy on LT outcomes in the UK and France. MethodsA retrospective analysis of all adult single or bilateral LT in France and the UK between 2010 and 2021. Recipients were stratified into 3 age groups: young (≤ 30 years), middle-aged (30 to 60) and older (≥60). Their donors were also stratified into 2 groups <60, ≥ 60. Primary graft dysfunction (PGD) rates and recipient survival was compared between matched and mismatched donor and recipient age groups. Propensity matching was employed to minimize covariate imbalances and to improve the internal validity of our results. ResultsOur study cohort was 4,696 lung transplant recipients (LTRs). In young and older LTRs, there was no significant difference in 1 and 5-years post-transplant survival dependent on the age category of the donor. Young LTRs who received older donor grafts had a higher risk of severe grade 3 PGD. ConclusionOur findings show that clinically usable organs from older donors can be utilized safely in LT, even for younger recipients. Further research is needed to assess if the higher rate of PGD3 associated with use of older donors has an effect on long-term outcomes.

Detection of Activated Pepsin in Bronchoalveolar Lavage and Acute Cellular Rejection in Lung Transplant Recipients

Detection of Activated Pepsin in Bronchoalveolar Lavage and Acute Cellular Rejection in Lung Transplant Recipients

Invasive Pulmonary Aspergillosis in Lung Transplant Recipients: Retrospective Clinical Analysis from a Tertiary Transplant Center.

Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral infections, it poses a similar or even higher mortality rate due to challenges in early diagnosis, limited treatment options, and various complications. Therefore, we aimed to evaluate the pulmonary aspergillosis cases in our tertiary lung transplant center. A retrospective analysis of 146 LTRs was performed. The demographic data, microbiological and histopathological test results, and radiological findings used for Aspergillus identification were recorded. Aspergillus spp. was detected in 13 of 146 LTRs (9%), mean age 42.5 ± 14.06 years, an average of 18.9 months after lung transplantation. 3 cases (23%) had Aspergillus growth in tissue culture, and 2 (15.4%) showed fungal elements with septal hyaline fibrils in tissue pathology. Aspergillus spp Polymerase chain reaction (PCR) was positive in bronchoalveolar lavage of 8 (61.5%) cases. In addition, 4 (30.7%) cases had relevant tomography findings. The most common pathogens were A. Terreus (21%), A. Fumigatus (14%), and A. Flavus (14%). The mortality rate was 15%. LTRs are at high risk of Aspergillus spp infections. Early diagnosis with microbiological, histopathological, and radiological tests, in addition to well-established prevention strategies, prophylaxis, and treatment will provide a better survival rate for patients.

Sex-based Disparities in Liver Transplantation for Hepatocellular Carcinoma and the Impact of the Growing Burden of NASH.

The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (β: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

Hernia Correction After Liver Transplantation Using Nonvascularized Fascia.

Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation. We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period. Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5-66 y), whereas the mean recipient age was 58 y (31-66 y). The median patient height and weight were 163 cm (117-185 cm) and 76 kg (17-104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5-116 mo). The sizes of the aponeurotic defects varied from 6 × 6 to 25 × 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up. With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality.

The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Portal vein arterialization in 25 liver transplant recipients: A Latin American single-center experience.

Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis (PVT). The effect of PVA on portal perfusion and primary graft dysfunction (PGD) has not been assessed. To examine the outcomes of patients who required PVA in correlation with their LT procedure. All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed. To account for the time-sensitive effects of graft perfusion, patients were classified into two groups: prereperfusion (pre-PVA), if the arterioportal anastomosis was performed before graft revascularization, and postreperfusion (post-PVA), if PVA was performed afterward. The pre-PVA rationale contemplated poor portal hemodynamics, severe vascular steal, or PVT. Post-PVA was considered if graft hypoperfusion became evident. Conservative interventions were attempted before PVA. A total of 25 cases were identified: 15 before and 10 after graft reperfusion. Pre-PVA patients were more affected by diabetes, decompensated cirrhosis, impaired portal vein (PV) hemodynamics, and PVT. PGD was less common after pre-PVA (20.0% vs 60.0%) (P = 0.041). Those who developed PGD had a smaller increase in PV velocity (25.00 cm/s vs 73.42 cm/s) (P = 0.036) and flow (1.31 L/min vs 3.34 L/min) (P = 0.136) after arterialization. Nine patients required PVA closure (median time: 62 d). Pre-PVA and non-PGD cases had better survival rates than their counterparts (56.09 months vs 22.77 months and 54.15 months vs 31.91 months, respectively). This is the largest report presenting PVA in LT. Results suggest that pre-PVA provides better graft perfusion than post-PVA. Graft hyperperfusion could play a protective role against PGD.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures.

Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy. This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents. To compare the safety and efficacy profile of different stenting durations using Kaffes stents. Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query. Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records. The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months. Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for ≤ 120 d or > 120 d. During the study period, a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course. In 33 ERCPs, the stent was removed or exchanged on a 3-month interval. No pancreatitis, perforations or deaths occurred. Minor post-ERCP complications were similar between the 3-month (abdominal pain and intraductal migration) and 6-month (abdominal pain, septic shower and embedded stent) groups - 6.1% vs 9.1% respectively, P = 0.40. All strictures resolved at the end of the stenting course, but the stenting course was variable from 3 to 22 months. The recurrence rate for stenting courses lasting for up to 120 d was 71.4% and 21.4% for stenting courses of 121 d or over (P = 0.03). There were 28 patients that were treated with a single ERCP with Kaffes, 21 with removal after 120 d and 7 within 120 d. There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course (71.0% vs 10.0%, P = 0.01). Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Cefiderocol utilization in lung transplant recipients at a single center

Multidrug-resistant organisms are increasing and are a significant cause of mortality among lung transplant recipients (LTRs). To assist with this issue, novel pharmacotherapies are being developed. This study describes the utilization of a novel antibiotic, cefiderocol (FDC), in LTRs where limited data exists in the current literature. We primarily assessed the clinical indications, duration of therapy, resistance, and adverse effects. Conducted as a single-center retrospective review, this study included adult LTRs who received FDC for at least 24 h. Data, extracted from electronic medical records, encompassed patient demographics, transplant history, antimicrobial dosing, adverse effects, bacterial cultures, and outcomes. The research protocol received institutional review board approval. FDC exhibited effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 26% 30-day mortality and microbiological clearance observed in nine out of 13 cases. Notably, FDC was used in diverse clinical settings, including for prophylaxis, empiric, and targeted treatment. Further studies are needed to evaluate optimal clinical indications for FDC use in LTRs.

Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

Orthotopic liver transplant (OLT) represents the standard of care for managing patients affected by end-stage and life-threatening liver diseases. Although a significant improvement in surgical techniques, immunosuppressant regimens, and prompt identification of early post-transplant complications resulted in better clinical outcome and survival in OLT recipients, the occurrence of early bacterial infections still represents a remarkable cause of morbidity and mortality. In this scenario, beta-lactams are the most frequent antimicrobials used in critical OLT recipients. The aim of this narrative review was to provide a comprehensive overview of the pathophysiological issues potentially affecting the pharmacokinetics of beta-lactams and to identify potential strategies for maximizing the likelihood of attaining adequate pharmacokinetic/pharmacodynamic (PK/PD) targets of beta-lactams in critically ill OLT recipients. A literature search was carried out on PubMed-MEDLINE database (until 31st March 2024) in order to retrieve clinical trials, real-world observational evidence, and/or case series/reports evaluating the PK/PD of traditional and novel beta-lactams in settings potentially involving critically ill OLT recipients. Retrieved evidence were categorized according to the concepts of the so-called “antimicrobial therapy puzzle”, specifically assessing a) beta-lactam PK/PD features, with specific regard to aggressive PK/PD target attainment; b) site of infection, with specific regard to beta-lactam penetration in the lung, ascitic fluid, and bile; and c) pathophysiological alterations, focusing mainly on those specifically associated with OLT. Overall, several research gaps still exist in assessing the PK behavior of beta-lactams in critical OLT recipients. The impact of specific OLT-associated pathophysiological alterations on the attainment of optimal PK/PD targets may represent an important field in which further studies are warranted. Assessing the relationship between aggressive beta-lactam PK/PD target attainment and clinical outcome in critical OLT recipients will represent a major challenge in the next future.