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

BACKGROUND: 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. AIM: To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

COVID-19 Vaccine in Lung and Liver Transplant Recipients Exceeds Expectations: An Italian Real-Life Experience on Immunogenicity and Clinical Efficacy of BNT162b2 Vaccine.

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

Self-reported symptom occurrence and distress, and psychological well-being after liver transplantation - a descriptive cross-sectional study of Danish recipients.

Introduction: Symptom distress and impaired psychological well-being after liver transplantation may lead to limitations in everyday activities and lowered health-related quality of life. The aim of this nationwide, descriptive, and cross-sectional study was to explore self-reported symptom occurrence and distress, among Danish liver transplant recipients, and their association with self-reported psychological well-being as well as demographic, and clinical characteristics. Methods: Liver transplant recipients transplanted from 1990 to 2022 were included. All recipients were asked to complete the Organ Transplant Symptom and Wellbeing instruments consisting of two instruments measuring self-reported symptom occurrence and distress, respectively, as well as self-reported psychological well-being by the Psychological General well-being instrument. Results: Of 511 invited recipients 238 responded: 116 women and 122 men with a median post-transplant follow-up of 7.5 years (IQR 3.6-14.2 years). The most common single symptoms reported were decreased libido (18%), diarrhea (10%), and headache (8%). Sleep problems were the most common transplant-specific domain. 41% of the recipients reported poor psychological well-being, especially those who had undergone transplantation within the last 5 years, women, and younger recipients. Discussion: In the interest of equity, the fact that women reported a higher level of symptom distress than men requires attention. Research on symptom management support is warranted with interventions focusing on how to alleviate symptom distress, which might increase long-term survival, which has not improved in recent decades.

Outcomes of Liver Transplant Recipients Hospitalized With COVID-19: A Nationwide Analysis From the United States.

Introduction: Currently available data regarding the impact of liver transplantation on the outcomes of patients hospitalized with COVID-19 is conflicting. This study aims to compare the outcomes and resource utilization between patients with and without a history of liver transplant hospitalized with COVID-19. Methods and materials: This is a retrospective study using the National Inpatient Sample. All adults hospitalized with COVID-19 in the year 2020 were included. Mortality was the primary outcome, while endotracheal intubation, length of hospital stay, and total hospital charges were the secondary outcomes. Results: Out of 1,050,720 adults admitted with COVID-19 as the primary diagnosis, 1,455 had a secondary diagnosis of liver transplant. Mortality was not significantly increased in transplant recipients (OR adjusted = 0.69, 95% CI: 0.46-1.03, P = 0.07). Intubation rates and total hospital charges did not differ significantly between liver transplant recipients and patients without a history of liver transplant receipt. LOS was shorter by a coefficient of almost two days in patients with a history of LT (P < 0.001). Conclusion: Liver transplant recipients do not appear to be at increased risk of severe COVID-19 and COVID-19 mortality.

Mindfulness-based cognitive therapy for adherence of immunosuppressive treatment in liver transplant recipients: A randomized controlled trial.

OBJECTIVE: The aim of this study was to analyze the effects of mindfulness-based cognitive therapy on the adherence of liver transplant recipients to immunosuppressive therapy with a randomized controlled design. METHOD: This randomized controlled trial was performed with 120 liver transplant recipients hospitalized at the liver transplant department of a research and practice hospital (n = 120). While we administered no intervention to the patients in the control group (n = 60), we provided Mindfulness-Based Cognitive Therapy to those in the experimental group (n = 60). We used the Mindful Attention Awareness Scale and the Immunosuppressant Therapy Adherence Scale to collect data. We utilized descriptive statistics, paired-samples t-tests, independent-samples t-tests, one-way analysis of variance, and chi-squared tests to analyze the data. RESULTS: After the intervention, the immunosuppressive therapy adherence levels of the experimental group increased significantly (p < 0.01). On the other hand, the control group had significantly higher adherence to immunosuppressive therapy and significantly higher levels of mindfulness in the pretest phase than it did in the posttest phase (p < 0.01). CONCLUSIONS: Complete adherence to immunosuppressive therapy is imperative for the prevention of graft rejection in liver transplant recipients. In our study, the experimental group equipped with enhanced mindfulness had higher adherence to immunosuppressive therapy. Therefore, the use of Mindfulness-Based Cognitive Therapy in the promotion of adherence to immunosuppressive therapy is recommended.

Anemia in liver transplant recipients: prevalence, severity, risk factors, and survival.

Information about anemia in liver transplant (LTx) recipients is scarce. We investigated the prevalence and severity of anemia before and within the first-year post-LTx, risk factors for having anemia before LTx, and 1-year survival according to anemia status before LTx. This retrospective cohort study received data from The Knowledge Center for Transplantation database at Rigshospitalet, Copenhagen, Denmark. Uni- and multivariate logistic regression were used to investigate factors associated with anemia and a Kaplan-Meier plot to illustrate the probability of survival. We included 346 first-time adult LTx recipients. The median age was 50 years (IQR: 42-57), and 203 (59%) were male. The prevalence of anemia before and 1-year post-LTx were 69 and 45%, respectively. Male sex (aOR 4.0 [95% CI: 2.2-7.2]; p < 0.001) and each unit increase in MELD score (aOR 1.2 [95% CI: 1.1-1.2]; p < 0.001) were positively associated with anemia before LTx. Compared to autoimmune liver diseases, LTx recipients with fulminant hepatic failure (aOR 0.03 [0.00-0.17]; p = 0.001) had lower odds for anemia. The 1-year survival in LTx recipients who had and did not have anemia before transplantation were 93 and 91% (p = 0.47). Anemia was frequent among LTx recipients, and anemia before LTx did not affect 1-year survival.

The applications of ECMO in liver transplant recipients.

Extracorporeal membrane oxygenation (ECMO) has emerged as a vital instrument for sustaining respiratory and cardiac functions when traditional methods have failed. Its function in managing acute pulmonary and cardiac challenges during liver transplantation (LT) has expanded significantly. While ECMO was initially viewed as a rescue strategy for acute intraoperative or posttransplant complications, its application now also encompasses the pretransplant stage of LT. Our review aims to thoroughly summarize both research and specific cases where ECMO has been utilized across pre- and perioperative phases in liver transplant recipients. By assessing the published literature, we discuss specific indications, the types of ECMO employed, their outcomes, and the unique challenges of applying ECMO during LT. In particular, the pretransplant use of ECMO is increasing, and its prudent introduction prior to LT, supported by meticulous planning, has the potential to optimize patient outcomes. It is challenging to manage liver transplant patients on ECMO. More research and experience are needed to refine the techniques and improve patient outcomes. Furthermore, decision-making must be tailored to each patient's unique circumstances, and a clear, practical, and well-defined plan for subsequent steps is essential.

Role of a Real-Time TDM-Based Expert Clinical Pharmacological Advice Program in Optimizing the Early Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Beta-Lactams among Orthotopic Liver Transplant Recipients with Documented or Suspected Gram-Negative Infections.

(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with continuous infusion (CI) beta-lactams optimized using a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program during the early post-surgical period. (2) Methods: OLT recipients admitted to the post-transplant intensive care unit over the period of July 2021-September 2023, receiving empirical or targeted therapy with CI meropenem, piperacillin-tazobactam, meropenem-vaborbactam, or ceftazidime-avibactam optimized using a real-time TDM-guided ECPA program, were retrospectively retrieved. Steady-state beta-lactam (BL) and/or beta-lactamase inhibitor (BLI) plasma concentrations (Css) were measured, and the Css/MIC ratio was selected as the best PK/PD target for beta-lactam efficacy. The PK/PD target of meropenem was defined as being optimal when attaining a fCss/MIC ratio > 4. The joint PK/PD target of the BL/BLI combinations (namely piperacillin-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam) was defined as being optimal when the fCss/MIC ratio > 4 of the BL and the fCss/target concentration (CT) ratio > 1 of tazobactam or avibactam, or the fAUC/CT ratio > 24 of vaborbactam were simultaneously attained. Multivariate logistic regression analysis was performed for testing potential variables that were associated with a failure in attaining early (i.e., at first TDM assessment) optimal PK/PD targets. (3) Results: Overall, 77 critically ill OLT recipients (median age, 57 years; male, 63.6%; median MELD score at transplantation, 17 points) receiving a total of 100 beta-lactam treatment courses, were included. Beta-lactam therapy was targeted in 43% of cases. Beta-lactam dosing adjustments were provided in 76 out of 100 first TDM assessments (76.0%; 69.0% decreases and 7.0% increases), and overall, in 134 out of 245 total ECPAs (54.7%). Optimal PK/PD target was attained early in 88% of treatment courses, and throughout beta-lactam therapy in 89% of cases. Augmented renal clearance (ARC; OR 7.64; 95%CI 1.32-44.13) and MIC values above the EUCAST clinical breakpoint (OR 91.55; 95%CI 7.12-1177.12) emerged as independent predictors of failure in attaining early optimal beta-lactam PK/PD targets. (4) Conclusion: A real-time TDM-guided ECPA program allowed for the attainment of optimal beta-lactam PK/PD targets in approximately 90% of critically ill OLT recipients treated with CI beta-lactams during the early post-transplant period. OLT recipients having ARC or being affected by pathogens with MIC values above the EUCAST clinical breakpoint were at high risk for failure in attaining early optimal beta-lactam PK/PD targets. Larger prospective studies are warranted for confirming our findings.

Evaluation of the humoral response to the third dose of SARS-COV-2 vaccines in liver transplant recipients.

Solid organ transplant recipients (SOTR) commonly develop an unsatisfactory humoral response to vaccines compared to immunocompetent individuals (IC). We have previously evaluated the humoral response in liver transplant recipients (LTR) who received two-dose vaccines against SARS-CoV-2 and reported that 38 % of LTR did not produce anti-Spike antibodies. Thus, we set out to evaluate the humoral response after the third dose of SARS-CoV-2 vaccines. For this purpose, samples from a cohort of 81 LTR and 27 IC were extracted between 21 and 90 days after the third dose. Serology for anti-Spike IgG antibodies and neutralizing antibodies against Wuhan, Delta and Omicron variants were evaluated. We found that 73.5 % of LTR were responders for anti-Spike IgG, while all the IC mounted a measurable response. LTR who responded to the third dose showed significantly lower anti-Spike IgG levels and neutralizing antibodies than IC. We found that there is less neutralization in LTR compared to IC across all variants. Specifically, the neutralization titers in both groups decrease when encountering the Delta variant, and this decline is even more pronounced with the Omicron variant, compared to the Wuhan variant. Furthermore, we identified that the use of high doses of mycophenolate and advanced age were factors that negatively affected the development of anti-Spike IgG antibodies. Regarding vaccine regimes, the regime viral vector/mRNA/mRNA elicited significantly higher responses in LTR compared to other vaccine schemes. In addition to the recommended and necessary booster doses in this population, strategies that achieve adequate immunization should be evaluated.

Caring for the Bone Health Among Liver Transplant Recipients.

Liver transplant outcomes have improved over the years, and currently, the quality of life and long-term well-being of these patients needs to be improved. Improving bone health goes a long way toward achieving this objective. Poor bone health (osteopenia and osteoporosis) although prevalent, is often overlooked owing to its asymptomatic nature. It can be complicated by debilitating fracture affecting quality of life. It is recommended to assess and optimize bone health prior to liver transplant. Multiple factors contribute to poor bone health in a liver transplant recipient and it is vital to understand and ameliorate these. A careful and targeted approach with inputs from multidisciplinary team involving transplant physician, endocrinologist, occupational therapist, nutritionist, and nursing personnel may often be required. In this review, we aim to concisely discuss the various aspects related to prevalence, pathophysiology, evaluation, treatment, and follow-up of bone disease among liver transplant recipients.

Third dose of BNT162b2 improves immune response in liver transplant recipients to ancestral strain but not Omicron BA.1 and XBB.

Vaccine immunogenicity in transplant recipients can be impacted by the immunosuppressive (IS) regimens they receive. While BNT162b2 vaccination has been shown to induce an immune response in liver transplant recipients (LTRs), it remains unclear how different IS regimens may affect vaccine immunogenicity after a third BNT162b2 dose in LTRs, which is especially important given the emergence of the Omicron sublineages of SARS-CoV-2. A total of 95 LTRs receiving single and multiple IS regimens were recruited and offered three doses of BNT162b2 during the study period. Blood samples were collected on days 0, 90, and 180 after the first BNT162b2 dose. At each time point, levels of anti-spike antibodies, their neutralizing activity, and specific memory B and T cell responses were assessed. LTRs receiving single IS regimens showed an absence of poor immunogenicity, while LTRs receiving multiple IS regimens showed lower levels of spike-specific antibodies and immunological memory compared to vaccinated healthy controls after two doses of BNT162b2. With a third dose of BNT162b2, spike-specific humoral, memory B, and T cell responses in LTR significantly improved against the ancestral strain of SARS-CoV-2 and were comparable to those seen in healthy controls who received only two doses of BNT162b2. However, LTRs receiving multiple IS regimens still showed poor antibody responses against Omicron sublineages BA.1 and XBB. A third dose of BNT162b2 may be beneficial in boosting antibody, memory B, and T cell responses in LTRs receiving multiple IS regimens, especially against the ancestral Wuhan strain of SARS-CoV-2. However, due to the continued vulnerability of LTRs to presently circulating Omicron variants, antiviral treatments such as medications need to be considered to prevent severe COVID-19 in these individuals.

The effect of post-traumatic growth on recovery in liver transplant recipients.

Aim: In our study, we examined the effect of post-traumatic growth on recovery in liver transplant recipients in the post-transplant period. Method: This research was performed as a descriptive and cross-sectional study with the participation of 218 patients who had liver transplantation at the liver transplant institute of a research and training hospital. The personal information form, the Post-Traumatic Growth Inventory, and the Recovery Assessment Scale were used in the data collection process. The Statistical Package for Social Science 25.0 was utilized in the data analysis process. Findings: In the research, of all participant liver transplant recipients, 67.8% were aged 45-64 years, 34.4% had incomes below expenses, and 91.7% had living donor liver transplantation. Besides, it was found that participants who had living donor liver transplantation obtained higher mean scores from both the Post-Traumatic Growth Inventory and the Recovery Assessment Scale than participants who had cadaveric donor liver transplantation, and likewise, participants who had past surgery experiences obtained higher mean scores from both the Post-Traumatic Growth Inventory and the Recovery Assessment Scale than participants who had no past surgery experience (p < 0.05). Moreover, there was a statistically significant positive linear relationship between participant liver transplant recipients' Post-Traumatic Growth Inventory and Recovery Assessment Scale scores. Conclusion: Post-traumatic growth supports recovery. Also, social support and a good economic situation are other parameters that promote recovery. In the two-year process during which the treatment is intensively applied to liver transplant recipients following the transplantation surgery, it is important to enable patients to find more meaning in life and to find solutions that facilitate recovery.

Therapeutic Physical Exercise Programs in the Context of NASH Cirrhosis and Liver Transplantation: A Systematic Review.

In recent years, various physical exercise interventions have been developed with a view to reducing comorbidity and morbidity rates among patients with chronic diseases. Regular physical exercise has been shown to reduce hypertension and mortality in patients with type 2 diabetes. Diabetes and obesity are often associated with the development of nonalcoholic fatty liver disease, which can lead to liver fibrosis and then (in some cases) nonalcoholic steatohepatitis cirrhosis. We searched the literature for publications on personalized physical exercise programs in cirrhotic patients before and after liver transplantation. Eleven studies in cirrhotic patients and one study in liver transplant recipients were included in the systematic review, the results of which were reported in compliance with the preferred reporting items for systematic reviews and meta-analyses guidelines. The personalized physical exercise programs lasted for 6 to 16 weeks. Our review evidenced improvements in peak oxygen consumption and six-minute walk test performance and a reduction in the hepatic venous pressure gradient. In cirrhotic patients, personalized physical exercise programs improve quality of life, are not associated with adverse effects, and (for transplant recipients) might reduce the 90-day hospital readmission rate. However, none of the literature data evidenced reductions in the mortality rates before and after transplantation. Further prospective studies are needed to evaluate the benefit of long-term physical exercise programs in cirrhotic patients before and after liver transplantation.

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients.

Immunogenicity after SARS-CoV-2 vaccination is known to be impaired in liver transplant (LT) recipients, but the results after the application of a third dose show significant improvement in seroconversion rates. In the general population, the antibody response wanes over the course of time after two doses of the vaccination, but seems to be more robust after the application of three doses. Still, the durability of the antibody response in LT recipients who receive a third dose of SARS-CoV-2 vaccination has not been analyzed yet. We therefore assessed antibody responses in a total of 300 LT recipients and observed antibody titers for six months each after patients had received the second and the third doses of the vaccination, explicitly excluding all patients who had suffered from SARS-CoV-2 infection. The initial antibody response was compared to a control group of 122 healthcare workers. After the application of two doses of the vaccination, 74% of LT recipients (158 out of 213) developed antibodies against SARS-CoV-2; this result depended significantly on whether the patients were taking the medication mycophenolate mofetil, and on the age of the patients. Antibody titers declined significantly within six months from 407 BAU/mL (IQR: 0-1865) to 105 BAU/mL (IQR: 0-145) (p ≤ 0.001), but increased after the application of the third vaccine dose in 92% of patients (105 out of 114), showing an antibody response (p ≤ 0.001). After a further six-month period, despite showing a decline from 2055 BAU/mL (IQR: 500 to >2080) to 1805 BAU/mL (IQR: 517 to >2080), the waning of antibody titers was not significant (p = 0.706), and antibody durability appeared to be more robust than that after the second dose. In conclusion, our study confirms the high efficacy of the application of a third dose of SARS-CoV-2 vaccination in LT recipients, and a reasonably sustained humoral response with superior durability in comparison to antibody kinetics after the application of the second dose of the vaccination.

Subjective Cognition is Related to Patient-Reported Symptom Distress and Work Productivity Among Liver Transplant Recipients.

Cognitive decline may prevent liver transplant (LT) recipients from staying healthy and independent. This study examined associations of objective and subjective, rated by LT recipients and caregivers, cognitive decline with patient-reported physical and psychological symptom distress, ability to perform household tasks, and workplace productivity among LT recipients. Sixty pairs of LT recipients and caregivers participated in this cross-sectional study. Subjective cognition was measured by the Everyday Cognition. Objective cognition was assessed with four cognitive tests, including the Repeatable Battery for the Assessment of Neuropsychological Status. Patient-reported outcomes were assessed with the Rotterdam Symptom Checklist-Modified, Profile of Mood States-Short Form, Creative Therapy Consultants Homemaking Assessment, and Work Limitations Questionnaire. Linear regression analyses related objective and subjective cognition to the patient-reported outcomes. While objective cognitive decline was not associated with any patient-reported outcomes, subjective cognitive decline was significantly associated with the outcomes. Higher LT recipient self-rated cognitive decline was associated with higher physical symptom distress ( ß = 0.30, p = 0.006) and workplace productivity loss ( ß = 14.85, p < 0.0001). Higher caregiver-rated cognitive decline was associated with lower household tasks performance ( ß = -18.55, p = 0.015). Findings suggest to consider subjective cognition when developing an individualized post-transplant care plan.

The Influence of Liver Transplant on Serum Cholinesterase Levels: A Case Report.

Cholinesterase is a serum enzyme synthesized mainly by the hepatocyte. Serum cholinesterase levels tend to decrease in time in patients with chronic liver failure and can indicate the intensity of liver failure. The lower the value of serum cholinesterase, the higher the possibility of liver failure. A reduction in liver function induced a drop in the level of serum cholinesterase. We present a patient with end-stage alcoholic cirrhosis and severe liver failure that received a liver transplant from a deceased donor. We compared blood tests and serum cholinesterase before and after the liver transplant. The hypothesis is that the value of serum cholinesterase increases after a liver transplant, and we noticed a significant increase in cholinesterase levels after the transplant. Serum cholinesterase activity increases after a liver transplant and it indicates that the liver function reserve will reach a higher level after the transplant, according to the new liver function reserve.

Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave.

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

Individual dose recommendations for drug interaction between tacrolimus and voriconazole in adult liver transplant recipients: A semiphysiologically based population pharmacokinetic modeling approach.

The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.