Adult Liver Transplant Recipients Research Articles

SAT260 - The portrait of adult liver transplant recipients in the United States from 2002 to 2020

SAT260 - The portrait of adult liver transplant recipients in the United States from 2002 to 2020

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Cirrhotic cardiomyopathy: Appraisal of the original and revised criteria in predicting posttransplant cardiac outcomes.

Cardiovascular disease (CVD) significantly contributes to morbidity and mortality after liver transplantation (LT). Cirrhotic cardiomyopathy (CCM) is a risk factor for CVD after transplant. CCM criteria were originally introduced in 2005 with a revision proposed in 2020 reflecting echocardiographic technology advancements. This study assesses the two criteria sets in predicting major adverse cardiac events (MACE) after transplant. This single-center retrospective study reviewed adult LT recipients between January 1, 2009, and December 31, 2018. Patients with insufficient pre-LT echocardiographic data, prior ischemic heart disease, portopulmonary hypertension, or longitudinal care elsewhere were excluded. The primary composite outcome was MACE (arrhythmia, heart failure, cardiac arrest, and/or cardiac death) after transplant. Of 1165 patients, 210met the eligibility criteria. CCM was present in 162 patients (77%) per the original criteria and 64 patients (30%) per the revised criteria. There were 44 MACE and 31 deaths in the study period. Of the deaths, 38.7% occurred secondary to CVD. CCM defined by the original criteria was not associated with MACE after LT (p=0.21), but the revised definition was significantly associated with MACE (hazard ratio [HR], 1.93; 95% confidence interval, 1.05-3.56; p=0.04) on multivariable analysis. Echocardiographic variable analysis demonstrated low septal e' as the most predictive variable for MACE after LT (HR, 3.45; p<0.001). CCM, only when defined by the revised criteria, was associated with increased risk for MACE after LT, validating the recently revised CCM definition. Abnormal septal e', reflecting impaired relaxation, appears to be the most predictive echocardiographic criterion for MACE after LT.

Incidence and risk factors for the development of cytomegalovirus viremia in a steroid sparing liver transplant center.

BackgroundCytomegalovirus (CMV) is a common opportunistic infection in patients after liver transplant (LT). Guidelines recommend 900 mg daily of valganciclovir; however, valganciclovir commonly causes dose‐dependent hematologic toxicities. Use of a low‐dose valganciclovir (450 mg) has been used to prevent these adverse effects, but the data regarding this dosing strategy are not as robust in a steroid sparing LT center.MethodsRetrospective chart review of adult LT recipients between January 1, 2008 and June 30, 2019. All patients received low‐dose valganciclovir 450 mg PO daily for CMV prophylaxis. Primary outcome was the incidence of CMV viremia in LT recipients at 12 months post‐LT. Secondary outcomes include time to CMV viremia, risk factors for the development of CMV viremia, and incidence of breakthrough CMV viremia while on valganciclovir prophylaxis.ResultsA total of 266 patients were included. Overall, the majority were male (63.2%) and Caucasian (45.5%). The most common indication for transplant was decompensated cirrhosis (82%). The incidence of CMV at 1 year posttransplant was 7.9%. Independent risk factors included high risk status (OR 5.97, 95% CI 2.14–16.61, p = .001) as well as having an episode of rejection (OR 5.99, 95% CI 2.16–16.66, p = .001).ConclusionLow‐dose valganciclovir can be effective in the prevention of CMV viremia in LT patients and may be a beneficial strategy for CMV prophylaxis in a steroid‐sparing transplant center. Further studies may be needed to determine appropriate length of prophylaxis therapy for different risk groups.

Infectious complications in acute graft‐versus‐host disease after liver transplantation

Graft-versus-hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5-99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin-resistant enterococci and gram-negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia-these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired.

In Vitro Predictive Dissolution Test Should Be Developed and Recommended as a Bioequivalence Standard for the Immediate-Release Solid Oral Dosage Forms of the Highly Variable Mycophenolate Mofetil.

The prodrug mycophenolate mofetil (MMF), which is presystemically hydrolyzed into the pharmacologically active compound mycophenolic acid (MPA), has been widely used for the prophylaxis of acute allograft rejection in solid organ transplantation. However, the huge variability in the plasma concentration level makes the development of MMF drug products difficult due to the great challenge of meeting the traditional bioequivalence (BE) limits. Numerous models have been developed in the past decade to explain the variability, with the emphasis on characterizing the enterohepatic circulation. While the variability arising from systemic appearance can also contribute to the remarkable MPA variability to a great extent, it has been ignored for long for this Biopharmaceutics Classification System class 2 drug. To improve the design of the BE study for this highly variable (HV) drug, the variability of MMF pharmacokinetic (PK) profiles focusing on the absorption process was explored in a population approach. A total of 81 Chinese adult liver transplant recipients were enrolled and had their plasma concentrations of MPA and its metabolites measured by HPLC during one visit or multiple visits in a long-term MMF regimen. The population models were developed using NONMEM, and the data and the results of the model were analyzed by R. Two population PK models of MMF focusing on the absorption process were developed based on the plasma concentrations of MPA and its major metabolite 7-O-MPA-β-glucuronide (MPAG). The MPA PK profiles were best characterized by a two-compartment disposition model with zero inter-individual variability (IIV) of elimination coefficient (K20), lag time, but considerable intra-individual variability (IAV) in the form of inter-occasion variability regarding systemic appearance coefficient, K20, and central volume of distribution, when just using MPA plasma concentrations as observations. The second model took into consideration the EHC by including MPAG profiles as well. The results from both models showcased that the IAV played a far more significant role than the IIV in accounting for the variability of the MMF systemic appearance. This is in line with what was found in the BE study: the within-subject variability (WSV) of BE measures largely exceeded the corresponding between-subject variability. The great WSV of MMF can be mechanistically explained by the interplay of dissolution and solubility with the gastrointestinal (GI) physiological dynamics, especially the gastric emptying (GE) in the fasting state regulated by migrating motor complex, and GE and pH variations in the fed state by the caloric content with irregular patterns of GI motility and secretion. The results implied that for the immediate-release solid oral dosage forms of MMF, running a regular in vitro dissolution test for the fasting state and developing a predictive in vitro dissolution test with sufficient simulation of the GE dynamics and proximal small intestinal pH fluctuations for the fed state would be excellent surrogates for the in vivo BE test. Furthermore, a physiologically based predictive in vitro dissolution test under both fasting and fed conditions would be a new trend for the BE studies of all other HV drug products.

Outcome of liver transplantation with grafts from brain-dead donors treated with dual hypothermic oxygenated machine perfusion, with particular reference to elderly donors

Prompted by the utilization of extended criteria donors, dual hypothermic oxygenated machine perfusion (D‐HOPE) was introduced in liver transplantation to improve preservation. When donors after neurological determination of death (DBD) are used, D‐HOPE effect on graft outcomes is unclear. To assess D‐HOPE value in this setting and to identify ideal scenarios for its use, data on primary adult liver transplant recipients from January 2014 to April 2021 were analyzed using inverse probability of treatment weighting, comparing outcomes of D‐HOPE‐treated grafts (n = 121) with those preserved by static cold storage (n = 723). End‐ischemic D‐HOPE was systematically applied since November 2017 based on donor and recipient characteristics and transplant logistics. D‐HOPE use was associated with a significant reduction of early allograft failure (OR: 0.24; 0.83; p = .024), grade ≥3 complications (OR: 0.57; p = .046), comprehensive complication index (−7.20 points; p = .003), and improved patient and graft survival. These results were confirmed in the subset of elderly donors (>75‐year‐old). Although D‐HOPE did not reduce the incidence of biliary complications, its use was associated with a reduced severity of ischemic cholangiopathy. In conclusion, D‐HOPE improves postoperative outcomes and reduces early allograft loss in extended criteria DBD grafts.

The role of extracorporeal membrane oxygenation as salvage therapy in adult liver transplant recipients: A high-volume transplantation center experience

The role of extracorporeal membrane oxygenation as salvage therapy in adult liver transplant recipients: A high-volume transplantation center experience

The use of transient elastography in identifying sub-clinical chronic ductopenic rejection in adult liver transplant recipients: A case series

BackgroundTransient elastography has become a standard tool for the accurate non-invasive assessment of liver stiffness and fat content. Liver transplant recipients can develop allograft fibrosis during long-term follow-up despite normal or mildly abnormal liver chemistries. Tapering of immunosuppression in long-term liver transplant survivors is performed relying solely on liver chemistries. It is important to know if underlying liver histology would be abnormal or if rejection was present as this would alter the desire to decrease stable maintenance doses of immunosuppression. MethodsWe present our experience of five liver transplant recipients who had transient elastography performed prior to consideration of weaning of their immunosuppression. ResultsAll five patients showed signs of elevated liver stiffness on transient elastography in the setting of normal to slightly abnormal liver tests with very stable immunosuppressant doses. This prompted the performance of liver biopsies which demonstrated immune-mediated liver injury and thus negated the immunosuppression withdrawal. ConclusionTransient elastography has utility as a non-invasive method to evaluate allograft health in long-term liver transplant survivors and can be useful in the decision-making process for immunosuppression weaning.

Intraoperative risk factors of acute kidney injury after liver transplantation.

Acute kidney injury (AKI) is one of the most common complications of liver transplantation (LT). We examined the impact of intraoperative management on risk for AKI following LT. In this retrospective observational study, we linked data from the electronic health record with standardized transplant outcomes. Our primary outcome was stage 2 or 3 AKI as defined by Kidney Disease Improving Global Outcomes guidelines within the first 7 days of LT. We used logistic regression models to test the hypothesis that the addition of intraoperative variables, including inotropic/vasopressor administration, transfusion requirements, and hemodynamic markers improves our ability to predict AKI following LT. We also examined the impact of postoperative AKI on mortality. Of the 598 adult primary LT recipients included in our study, 43% (n = 255) were diagnosed with AKI within the first 7 postoperative days. Several preoperative and intraoperative variables including (1) electrolyte/acid‐base balance disorder (International Classification of Diseases, Ninth Revision codes 253.6 or 276.x and International Classification of Diseases, Tenth Revision codes E22.2 or E87.x, where x is any digit; adjusted odds ratio [aOR], 1.917, 95% confidence interval [CI], 1.280–2.869; p = 0.002); (2) preoperative anemia (aOR, 2.612; 95% CI, 1.405–4.854; p = 0.002); (3) low serum albumin (aOR, 0.576; 95% CI, 0.410–0.808; p = 0.001), increased potassium value during reperfusion (aOR, 1.513; 95% CI, 1.103–2.077; p = 0.01), and lactate during reperfusion (aOR, 1.081; 95% CI, 1.003–1.166; p = 0.04) were associated with posttransplant AKI. New dialysis requirement within the first 7 days postoperatively predicted the posttransplant mortality. Our study identified significant association between several potentially modifiable variables with posttransplant AKI. The addition of intraoperative data did not improve overall model discrimination.

Perioperative management of adult living donor liver transplantation: Part 1 - recipients.

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.

Incidence and Impact of COVID-19 Cases in Brazilian Liver Transplant Recipients: An Academic, Single-center Experience

BackgroundCurrent literature reports diverge on the impact of COVID-19 in liver transplant (LT) recipients. Literature findings often report conflicting results, relying on small sample sizes, limited ethnic variability, and nonstandardized methodologies. Notably, there are no studies on this topic regarding Latin American populations. This study seeks to report the impact of COVID-19, disease characteristics, and progression in LT recipients in a Latin American academic center environment.MethodsThe study design was a historic cohort, including adult LT recipient patients with suspected or confirmed COVID-19 who sought care between December 2019 to October 2021. The primary end point was defined as COVID-19–related death. Demographic, clinical, and laboratory data was also collected.ResultsTwenty-seven patients were included, representing a 3.5% incidence within 752 patients in the follow-up. The mean age and years from transplantation were 54 (SD ± 11) and 6.3 years (SD ± 5.4), respectively. Most patients were white (23 - 85.2%) and male (21 - 25.2%). The hospitalization rate was 55.6%, and 5 patients (18.5%), all of whom subsequently died, were admitted to the intensive care unit. Neither the presence of comorbidities nor advanced age were related to lethality. Patients with immunosuppression modifications (P = 0.039) or isolated tacrolimus suspension (P = 0.006) were associated with increased mortality.ConclusionsThis study described COVID-19 infections in LT recipients in Latin American populations. This group was not affected by common factors associated with higher lethality, and displayed a tendency toward lower hospitalization rates. Our study concurred with previously reported evidence of a protective association of tacrolimus maintenance during treatment in LT recipients affected by COVID-19.

Textbook Outcome as a Quality Metric in Liver Transplantation.

Background.Quality in liver transplantation (LT) is currently measured using 1-y patient and graft survival. Because patient and graft survival rates now exceed 90%, more informative metrics are needed. Textbook outcomes (TOs) describe ideal patient outcomes after surgery. This study critically evaluates TO as a quality metric in LT.Methods.United Network for Organ Sharing data for 25 887 adult LT recipients were used to define TO as patient and graft survival >1 y, length of stay ≤10 d, 0 readmissions within 6 mo, absence of rejection, and bilirubin <3 mg/dL between months 2 and 12 post-LT. Univariate analysis identified donor and recipient characteristics associated with TO. Covariates were analyzed using purposeful selection to construct a multivariable model, and impactful variables were incorporated as linear predictors into a nomogram. Five-year conditional survival was tested, and center TO rates were corrected for case complexity to allow for center-level comparisons.Results.The national average TO rate is 37.4% (95% confidence interval, 36.8%-38.0%). The hazard ratio for death at 5 y for patients who do not experience TO is 1.22 (95% confidence interval, 1.11-1.34; P ≤ 0.0001). Our nomogram predicts TO with a C-statistic of 0.68. Center-level comparisons identify 31% of centers as high performing and 21% of centers as below average. High rates of TO correlate only weakly with center volume.Conclusions.The composite quality metric of TO after LT incorporates holistic outcome measures and is an important measure of quality in addition to 1-y patient and graft survival.

A Systematic Review of the Literature on Chronic Kidney Disease Following Liver Transplantation.

Chronic kidney disease (CKD) is a serious comorbidity affecting liver transplant recipients (LTRs). Calcineurin inhibitor dosing minimization protocols and everolimus use purportedly increased from 2010, potentially impacting CKD development. This systematic literature review was designed to identify CKD incidence in adult LTRs, focusing on studies published from 2010 onwards.PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for papers reporting renal function (glomerular filtration rate [GFR]; estimated GFR [eGFR] or Chronic Kidney Disease Epidemiology Collaboration) for adult LTRs ≥6 months after transplantation. Primary outcome: renal function ≥6 months after transplantation, with CKD stage. Bias was assessed using the Cochrane Collaboration bias tool and by reviewing disclosures/industry funding.Of 3960 records identified, 14 publications were included. In at least 1 study arm, mean GFR/eGFR remained stable/improved temporally in 4 and decreased in 8 publications. Where GFR/eGFR decreased, mean eGFR was 71.4–119.6 mL/min/1.73 m2 (CKD stage 2-stage 1) across studies at baseline, and was 77.2 and 79.1 mL/min/1.73 m2 (stage 2) at 12 months. The proportion of patients with CKD increased between baseline and follow-up; 23.2–36.8% of patients had CKD stage 3a or higher at 12 months (2 studies). Rates ranged from 85.7–100% (6 months) for patient survival, 81.0% (12 months) to 100.0% (17 months) for graft survival, and 0–40% (12 months) for acute rejection. Most studies carried risk of bias.Evidence of temporal renal function decline highlights the need for continuous renal monitoring of LTRs, particularly regarding potential CKD development/progression.

Comparison of Post-Transplantation Lymphoproliferative Disorder Risk and Prognostic Factors between Kidney and Liver Transplant Recipients.

Simple SummaryOrgan graft type is an independent risk factor for the development of PTLD. Due to small cohort sizes caused by the rarity of the disease, most studies and trials are performed on populations of recipients of various organ graft types. Our study is a first direct comparison of the effect of different risk and prognostic factors between kidney and liver transplant recipients (KTRs and LTRs, respectively). We have demonstrated that the analysis of risk factors based on the general solid organ transplant recipient population is inconsistent with the results obtained through the analysis of single organ graft type cohorts. The risk of PTLD is lower in KTRs who are female, <45 years old at transplantation, or treated with cyclosporin. Based upon our findings, we are confident that the type of organ graft is an overriding factor in PTLDs’ development and course.Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD’s risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies.

Outcomes in Adult Liver Transplant Recipients Using Pediatric Deceased Donor Liver Grafts.

Background.The use of pediatric grafts for liver transplantation (LT) into adult recipients is rare, and reported outcomes are conflicting. The aim of this study is to evaluate the outcomes in adult recipients following LT with grafts from deceased pediatric donors.Methods.A retrospective study identifying adult LT between 2010 and 2020 using pediatric deceased donor liver grafts was conducted. Adults undergoing LT with deceased donor pediatric grafts (age ≤ 12) were identified and matched 1:2 with adults receiving adult grafts (age ≥ 18) based on recipient age (±10 y), model for end-stage liver disease (MELD) score at transplant (±5 points) and etiology of liver disease. To assess real liver size differences between the pediatric-donor and adult-donor groups, patients receiving a graft from a donor between 13 and 17 y were excluded from the main analysis and studied independently. Outcomes between the groups were compared. Complication rates were identified and graded using Clavien–Dindo classification. Graft and patient survival were assessed by Kaplan–Meier curves.Results.Twelve adult LT recipients with whole liver grafts from deceased pediatric donors were matched with 24 adult recipients of adult donors. Recipient age and MELD score were similar between groups. Recipients of pediatric grafts were more likely to be female (66.7% versus 16.7%, P = 0.007) and leaner (body mass index = 24.4 versus 29.9, P = 0.013). Alcohol-related cirrhosis was the most prevalent liver disease etiology in both groups (P = 0.96). There was no significant difference in length of stay, readmissions, early complications, or major complications between groups. Vascular and biliary complication rates were similar. Actuarial graft and patient survival at 1, 3, and 5 y were 100/100/100 versus 96/96/96 (P = 0.48).Conclusions.Excellent patient and graft survival is achievable with LT using young pediatric deceased donor grafts in smaller adult recipients. Outcomes are comparable with recipients of age and MELD-matched adult donors. Careful donor MELD-score recipient matching and close monitoring for potential biliary and vascular complications are crucial to achieve acceptable outcomes.

Varying Utilization Rates but Superior Outcomes in Liver Transplantation From Hepatitis C-positive Donors in the United States: An Analysis of the OPTN/UNOS Database.

Liver transplantation (LT) from hepatitis C virus (HCV)-positive donors [antibody positive (Ab+) or nucleic acid test-positive (NAT+) donors] has been reported to achieve successful outcomes. However, donor and recipient selection has not been well-characterized. Data between 2015 and 2019 were obtained from the United Network for Organ Sharing database. The utilization rates and graft survival among 35 239 potential donors and 23 780 adult LT recipients were reviewed based on donor HCV Ab/NAT status. The utilization of Ab+/NAT+ donors was significantly reduced compared with HCV-negative donors (66.4% versus 80.0%, P < 0.001) among donors aged between 40 and 69 y. Recipients of livers from HCV-positive donors had lower laboratory and allocation Model for End-stage Liver Disease scores (both P < 0.001). HCV-positive donors were younger ( P < 0.001). Kaplan-Meyer survival curves demonstrated significantly superior 1-y graft survival in recipients of HCV-positive grafts compared with those from HCV-negative grafts ( P = 0.004; 97.1% in Ab-/NAT+, 93.9% in Ab+/NAT-, and 93.7% in Ab+/NAT+ versus 91.8% in Ab-/NAT-). Multivariate analysis for 1-y graft survival identified donor age [hazard ratio (HR) = 1.01; 95% confidence interval (CI), 1.00-1.01] and laboratory Model for End-stage Liver Disease score (HR = 1.01; 95% CI, 1.00-1.01) as independent predictors but not donor HCV status: HR 0.77' 95% CI, 0.58-1.02 in Ab+/NAT-; HR 0.82' 95% CI, 0.66-1.03 in Ab+/NAT+; and HR 0.39' 95% CI, 0.10-1.55 in Ab-/NAT+. More widespread utilization of HCV-positive donors, especially Ab+/NAT+ donors of age 40-69 y, may expand the donor pool without impairing short-term outcomes after LT.

Risk factors of invasive fungal infections in liver transplant recipients: A systematic review and meta-analysis

Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the highest mortality rate. However, risk factors associated with IFIs have only been evaluated in small single-center studies. We performed a meta-analysis by conducting a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of controlled trials. All case-control and cohort studies evaluating risk factors for IFIs in adult LTRs were screened. Utilizing a random-effects model, a multivariate analysis was completed, and 28 studies were eligible for meta-analysis. Rates of IFIs ranged from 1.4% to 32.7%. Previous antibiotic use (OR 9.3; 95% CI 3.2-27.0) and bacterial infection (OR 4.3; 95% CI 2.1-8.6) were risk factors of invasive candidiasis. Yet for invasive aspergillosis, posttransplant renal replacement therapy (OR 9.2; 95% CI 4.2-20.4), reoperation (OR 8.0; 95% CI 2.9-21.7), and cytomegalovirus infection (OR 6.2; 95% CI 2.0-19.3) were risk factors. The top independent risk factors for IFIs during studies from 2010 to 2019 were previous fungal colonization (OR 9.19; 95% CI 4.92-17.16), reoperation (OR 5.45; 95% CI 2.93-10.15), and previous bacterial infections (OR 3.81; 95% CI 2.13-6.83). These risk factors may be targeted by antifungal prophylaxis in LTRs.

COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study

Liver transplant (LT) recipients are vulnerable to SARS-CoV-2-infection (COVID-19), due to immunosuppression and comorbidities. This study aimed to evaluate the impact of COVID-19 on LT recipients compared to general population in the Campania region. In this prospective double-centre study, we enrolled all consecutive adult LT recipients with confirmed SARS-CoV-2-infection. Data were collected at diagnosis of COVID-19 and during follow-up and compared with the regional population. Thirty LT recipients (3.28%) developed SARS-CoV-2-infection (76.66% male, median age 62.61 years). Sixteen (53.33%) were symptomatic. Common symptoms were fever, cough, fatigue, and anosmia. Twenty-five (83.33%) were outpatients, 5 (16.66%) required hospitalization (6.66% admitted to Intensive Care Unit, 6.62% developed Acute Respiratory Distress Syndrome and 6.66% died). Immunosuppressors were in 3 (10%) patients. Incidence rate of COVID-19 was similar between LT patients and general population (3.28% vs 4.37%, p = 0.142) with higher rate of symptoms in LT patients (53.33% vs 15.87%, p < 0.000). At univariate analysis, hospitalization and case fatality rates were higher in LT patients compared to general population (16.66% vs 4.54%, p = 0.001; and 6.66% vs 1.76%, p = 0.041, respectively). At multivariable logistic regression analysis, LT patients with COVID-19 were more frequently symptomatic (OR 5.447 [95% CI 2.437–12.177], p < 0.000), whereas hospitalization and death for COVID-19 were not significatively associated with LT condition (p = 0.724 and p = 0.462, respectively) and were comparable with general population. LT is not a risk factor for acquiring COVID-19. Nonetheless, LT patients are more frequently symptomatic, although comparable to the general population for hospitalization rate and mortality.

Clinical course and outcomes of COVID-19 infection in liver transplant recipients: single-center cross-sectional study

Background. The novel coronavirus infection (COVID-19) pandemic has had a significant impact on all areas of health care system, including organ donation and transplantation. Despite this, there were no large Russian studies of COVID-19 course and outcomes in liver transplant recipients.The study purpose was to determine prevalence, clinical course, severity, outcomes of COVID-19, as well as to assess the safety and efficiency of vaccination for disease prevention in liver transplant recipients.Material and methods. 260 recipients (71% of all patients at risk of COVID-19 disease) who underwent liver transplantation at State Research Center – Burnasyan Federal Medical Biophysical Center from May 2010 to September 2021 were included in a single-center cross-sectional study. Data collection was performed during a telephone or face-to-face interview from September 6, 2021 to September 20, 2021. If patients were hospitalized with COVID-19, we also analyzed the results of laboratory and instrumental tests, other medical documentation.Results. By mid-September 2021, the incidence of COVID-19 after liver transplantation was 31% (75 cases in 260 recipients). Asymptomatic course was observed in 11 (15%) patients. Hospitalization was required in 18 (28%) cases. In one case, COVID-19 infection was the cause of death. Mortality and death rate in the study cohort were 1% (1/75) and 0.4% (1/260), respectively. Risk factors that statistically significantly increased the likelihood of infection with SARS-CoV-2 were contact with the patient (OR: 12.9; 95% CI: 6.6 - 25.0) and non-compliance with non-specific prophylaxis measures (OR: 2.0; 95 % CI: 1.1 - 3.7). The recipient's age of 60 years or more significantly increased the risk of severe infection (OR 5.0; 95% CI: 1.3 - 18.7). None of the immunosuppressive therapy regimens significantly increased the risk of severe disease. Tacrolimus monotherapy or in combination with other drugs reduced the risk of severe COVID-19 (OR: 0.2; 95% CI: 0.1 - 0.95). Vaccination against SARS-CoV-2, which was performed in 42 (17%) recipients, did not cause serious adverse events and significantly reduced the risk of COVID-19 disease (OR: 7.2; 95% CI: 1.7 - 31.3). The detection rate of specific IgG antibodies to SARS-CoV-2 was 94% in recipients who had undergone the disease and 45% among those vaccinated (p&lt;0.001). The achieved level of herd immunity against COVID-19 in the analyzed cohort was 48%. Conclusion. Adult liver transplant recipients are not at an excessive risk of COVID-19 disease. Compliance with preventive measures and vaccination can significantly reduce the risks of infection and severe infection. There is no objective evidence that immunosuppressive therapy increases the risk of severe COVID-19 in liver transplant recipients. In the context of the ongoing COVID-19 pandemic, tacrolimus monotherapy may be considered as a safe regimen of maintenance immunosuppression.