Clinical Impact and Risk Factors of Seizure After Liver Transplantation: A Nested Case-Control Study.

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23 kg/m2, donor age ≥45 years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome.

Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients.

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

High Number of Plasma Exchanges Increases the Risk of Bacterial Infection in ABO-incompatible Living Donor Liver Transplantation.

BACKGROUND: Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs. METHODS: A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group. RESULTS: The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection (P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001). CONCLUSIONS: A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.

Cumulative exposure to tacrolimus during early period after liver transplantation does not affect the recurrence of hepatocellular carcinoma.

The clinical effects of tacrolimus (TAC) exposure on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remain unclear. In this retrospective single centric study, 512 patients who underwent LT for HCC were divided into four groups according to cumulative exposure to tacrolimus (CET) during 3 months after LT: conventional (n = 218), aggressive minimization (n = 32), minimization (n = 161), and high exposure (n = 101). Impact of CET on HCC recurrence and death were analyzed. Compared with the conventional group, the other three CET groups showed a similar risk of HCC recurrence. The aggressive minimization group showed a higher risk [hazard ratio (HR) 5.64, P < 0.001] and the high exposure group showed a marginal risk (HR 1.67, P = 0.081) of overall death compared to the conventional group. CET during 3 months was not associated with HCC recurrence in the matched cohort and various subgroups. TAC minimization is not effective to prevent HCC recurrence but could result in higher mortality in LT recipients.

Unusual grafts for living-donor liver transplantation.

PURPOSE: Unusual grafts, including extended left liver plus caudate lobe, right anterior section, and right posterior section grafts, are alternatives to left and right lobe grafts for living-donor liver transplantation. This study aimed to investigate unusual grafts from the perspectives of recipients and donors. METHODS: From 2016 to 2021, 497 patients received living-donor liver transplantation at Severance Hospital. Among them, 10 patients received unusual grafts. Three patients received extended left liver plus caudate lobe grafts, two patients received right anterior section grafts, and five patients received right posterior section grafts. Liver volumetrics and anatomy were analyzed for all recipients and donors. We collected data on laboratory examinations (alanine aminotransferase, total bilirubin, international normalized ratio), imaging studies, graft survival, and complications. A 1:2 ratio propensity-score matching method was used to reduce selection bias and balance variables between the unusual and conventional graft groups. RESULTS: The median of Model for End-stage Liver Disease score of unusual graft recipients was 13.5 (interquartile range 11.5-19.3) and that of graft-recipient weight ratio was 0.767 (0.7-0.9). ABO incompatibility was observed in four cases. The alanine aminotransferase level, total bilirubin level, and international normalized ratio decreased in both recipients and donors. Unusual and conventional grafts had similar survival rates (p = 0.492). The right and left subgroups did not differ from each counter-conventional subgroup (p = 0.339 and p = 0.695, respectively). The incidence of major complications was not significantly different between unusual and conventional graft recipients (p = 0.513). Wound seromas were reported by unusual graft donors; the complication ratio was similar to that in conventional graft donors (p = 0.169). CONCLUSION: Although unusual grafts require a complex indication, they may show feasible surgical outcomes for recipients with an acceptable donor complication.

Predicted Impact of the Model for End-Stage Liver Disease 3.0 in a Region Suffering Severe Organ Shortage.

BACKGROUND: The model for end-stage liver disease 3.0 (MELD3.0) is expected to address the flaws of the current allocation system for deceased donor liver transplantation (DDLT). We aimed to validate MELD3.0 in the Korean population where living donor liver transplantation is predominant due to organ shortages. METHODS: Korean large-volume single-centric waitlist data were merged with the Korean Network for Organ Sharing (KONOS) data. The 90-day mortality was compared between MELD and MELD3.0 using the C-index in 2,353 eligible patients registered for liver transplantation. Patient numbers and outcomes were compared based on changes in KONOS-MELD categorization using MELD3.0. Possible gains in MELD points and reduced waitlist mortality were analyzed. RESULTS: MELD3.0 performed better than MELD (C-index 0.893 for MELD3.0 vs. 0.889 for MELD). When stratified according to the KONOS-MELD categories, 15.9% of the total patients and 35.2% of the deceased patients were up-categorized using MELD3.0 versus MELD categories. The mean gain of MELD points was higher in women (2.6 ± 2.1) than men (2.1 ± 1.9, P < 0.001), and higher in patients with severe ascites (3.3 ± 1.8) than in controls (1.9 ± 1.8, P < 0.001); however, this trend was not significant when the MELD score was higher than 30. When the possible increase in DDLT chance was calculated via up-categorizing using MELD3.0, reducible waitlist mortality was 2.7%. CONCLUSION: MELD3.0 could predict better waitlist mortality than MELD; however, the merit for women and patients with severe ascites is uncertain, and reduced waitlist mortality from implementing MELD3.0 is limited in regions suffering from organ shortage, as in Korea.

Survival benefit of living-donor liver transplantation in patients with a model for end-stage liver disease over 30 in a region with severe organ shortage: a retrospective cohort study.

BACKGROUND: The benefits of living-donor liver transplantation (LDLT) in patients with a high Model for End-stage Liver Disease (MELD) score (who have high waitlist mortality) are unclear. Regional availability of deceased-donor organs must be considered when evaluating LDLT benefits. The authors aimed to compare the survival benefit of intended-LDLT to awaiting deceased-donor liver transplantation (DDLT) in patients with a MELD score greater than or equal to 30 in a region with severe organ shortage. MATERIALS AND METHODS: This retrospective review included 649 patients with a MELD score greater than or equal to 30 placed on the liver transplantation waitlist. They were divided into intended-LDLT ( n =205) or waiting-DDLT ( n =444) groups based on living-donor eligibility and compared for patient survival from the time of waitlisting. Post-transplantation outcomes of transplant recipients and living donors were analyzed. RESULTS: Intended-LDLT patients had higher 1-year survival than waiting-DDLT patients (53.7 vs. 28.8%, P <0.001). LDLT was independently associated with lower mortality [hazard ratio (HR), 0.62; 95% CI, 0.48-0.79; P <0.001]. During follow-up, 25 patients were de-listed, 120 underwent LDLT, 170 underwent DDLT, and 334 remained on the waitlist. Among patients undergoing transplantation, the risk of post-transplantation mortality was similar for LDLT and DDLT after adjusting for pretransplantation MELD score (HR, 1.86; 95% CI, 0.73-4.75; P =0.193), despite increased surgical complications after LDLT (33.1 vs. 19.4%, P =0.013). There was no mortality among living-donors, but 4.2% experienced complications of grade 3 or higher. CONCLUSIONS: Compared to awaiting DDLT, LDLT offers survival benefits for patients with a MELD score greater than or equal to 30, while maintaining acceptable donor outcomes. LDLT is a feasible treatment for patients with a MELD score greater than or equal to 30 in regions with severe organ shortages.

Effect of statins on the recurrence of hepatocellular carcinoma after liver transplantation: An illusion revealed by exposure density sampling.

BACKGROUND: Statins have been reported to reduce overall death and hepatocellular carcinoma (HCC) recurrence in liver transplantation (LT) recipients. However, previous retrospective studies have significant flaws in immortal time bias. METHODS: Using data from 658 patients who received LT for HCC, we matched 140 statin users with statin nonusers in a 1:2 ratio at the time of the first statin administration after LT using the exposure density sampling (EDS). The propensity score, calculated using baseline variables (including explant pathology), was used for EDS to equilibrate both groups. HCC recurrence and overall death were compared after adjusting for information at the time of sampling. RESULTS: Among statin users, the median time to statin start was 219 (IQR 98-570) days, and intensity of statins was mainly moderate (87.1%). Statin users and nonusers sampled using EDS showed well-balanced baseline characteristics, including detailed tumour pathology, and similar HCC recurrence with cumulative incidences of 11.3% and 11.8% at 5 years, respectively (p = .861). In multivariate Cox models (HR 1.04, p = .918) and subgroup analyses, statins did not affect HCC recurrence. Conversely, statin users showed a significantly lower risk of overall death than nonusers (HR 0.28, p < .001). There was no difference in the type and intensity of statin usage between statin users who experienced HCC recurrence and those who did not. CONCLUSION: Upon controlling immortal time bias by EDS, statins did not affect HCC recurrence but reduced mortality after LT. Statin usage is encouraged for survival benefits but not for preventing HCC recurrence in LT recipients.

Risk Factors for Cytomegalovirus Infection and Its Impact on Survival after Living Donor Liver Transplantation in South Korea: A Nested Case-Control Study.

Cytomegalovirus (CMV), a common pathogen, causes infectious complications and affects long-term survival after transplantation. Studies examining living donor liver transplantation (LDLT) are limited. This study analyzed the risk factors for CMV infection and its impact on the survival of LDLT patients. A nested case-control design retrospectively analyzed data from 952 patients who underwent LDLT from 2005-2021. The incidence of CMV infection for the study cohort was 15.2% at 3 months for LDLT patients managed preemptively. Patients with CMV infections were matched with those without the infection at corresponding time points (index postoperative day) in a 1:2 ratio. Graft survival was significantly lower in the CMV infection group than in the control group. CMV infection was an independent risk factor for graft survival in the matched cohort (HR 1.93, p = 0.012). Independent risk factors for CMV infection were female sex (HR 2.4, p = 0.003), pretransplant MELD (HR 1.06, p = 0.004), pretransplant in-hospital stay (HR 1.83, p = 0.030), ABO incompatibility (HR 2.10, p = 0.009), donor macrovesicular steatosis ≥10% (HR 2.01, p = 0.030), and re-operation before index POD (HR 2.51, p = 0.035). CMV infection is an independent survival risk factor, and its risk factors should be included in the surveillance and treatment of CMV infections after LDLT.

Risk factors for late-onset Pneumocystis jirovecii pneumonia in liver transplant recipients.

OBJECTIVES: The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis. METHODS: Among 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP. RESULTS: After 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP. CONCLUSION: Late-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication.

Incidence, mortality, and risk factors associated with carbapenem-resistant Acinetobacter baumannii bacteremia within 30 days after liver transplantation.

Carbapenem-resistant Acinetobacter baumannii bacteremia (CRAB-B) is a fatal infectious complication of liver transplantation (LT). This study investigated the incidence, effects, and risk factors associated with CRAB-B during the early post-LT period. Among 1051 eligible LT recipients, 29 patients experienced CRAB-B within 30 days of LT with a cumulative incidence of 2.7%. In the patients with CRAB-B (n = 29) and matched controls (n = 145) by nested-case control design, the cumulative incidence of death on days 5, 10, and 30 from the index date was 58.6%, 65.5%, and 65.5%, and 2.1%, 2.8%, and 4.2%, respectively (p < .001). Pre-transplant MELD (OR 1.11, 95% confidence interval [CI] 1.04-1.19, p = .002), severe encephalopathy (OR 4.62, 95% CI 1.24-18.61, p = .025), donor body mass index (OR .57, 95% CI .41-.75, p < .001), and reoperation (OR 6.40, 95% CI 1.19-36.82, p = .032) were independent risk factors for 30-day CRAB-B. CRAB-B showed extremely high mortality within 30 days after LT, especially within 5 days after its occurrence. Therefore, assessment of risk factors and early detection of CRAB, followed by proper treatment, are necessary to control CRAB-B after LT.

Successful Recovery After Veno-Arterio-Venous Extracorporeal Membrane Oxygenation Immediately Before Liver Transplantation in Multi-Organ Failure Including Acute Respiratory Distress Syndrome: A Case Report.

Extracorporeal membrane oxygenation (ECMO) has emerged as an alternative treatment to conventional ventilation maneuvers in the nontransplantation literature to support acute respiratory distress syndrome. However, the role of ECMO in transplant is unclear, and few case reports have described using ECMO pretransplant. We discuss the successful use of veno-arteriovenous ECMO as a bridge therapy to deceased donor liver transplant (LT) in acute respiratory distress syndrome. Because the incidence of severe pulmonary complications resulting in acute respiratory distress syndrome with multiorgan failure is rare before LT, determining the usefulness of ECMO is challenging. However, in acute but reversible respiratory failure and cardiovascular failure, veno-arteriovenous ECMO provides a useful therapeutic option as a bridge for patients awaiting LT and should be considered if available even in multiorgan failure.

Antiplatelet Drugs on the Recurrence of Hepatocellular Carcinoma after Liver Transplantation.

Previous studies reported suppressive effects of antiplatelet agents on hepatocellular carcinoma (HCC); however, this has never been assessed in patients who underwent liver transplantation (LT). This retrospective observational study used data from LT recipients with pre-transplant HCC in a single tertiary hospital. The study population was divided into two groups according to the use of antiplatelet agents for >90 days within the study period (377 antiplatelet groups versus 91 non-antiplatelet groups). Matched groups containing 79 patients in each group were also compared regarding HCC-recurrence and HCC-related mortality, which were analyzed by treating non-HCC death as a competing risk. In Kaplan−Meier analyses of the matched cohort, the 5-year cumulative incidences of HCC recurrence and HCC-specific death were similar between the antiplatelet (p = 0.876) and non-antiplatelet groups (p = 0.701). All-cause and non-HCC deaths were also similar between the two groups (p = 0.867 and p = 0.413, respectively). In multivariable analyses of the entire cohort, antiplatelet use was not associated with HCC recurrence (hazard ratio [HR] 1.37, p = 0.300) or HCC-specific death (HR 1.54, p = 0.310). Therefore, unlike the usual setting with liver disease, antiplatelet therapy did not affect HCC recurrence or HCC-specific mortality when used after LT.

Outcomes of Living-Donor Kidney Transplantation in Female Recipients with Possible Pregnancy-Related Pre-Sensitization According to Donor Relationship.

BACKGROUND Given that pregnancy is an immune-sensitizing event, female kidney transplant recipients who receive allografts from their offspring or husbands may have a higher risk of rejection and graft failure due to pre-sensitization acquired during pregnancy or childbirth. We investigated the association between donor relatedness (i.e., offspring, husband, unrelated) and graft survival among female living-donor kidney transplant (LDKT) recipients with pregnancy histories. MATERIAL AND METHODS From January 2009 to January 2018, a total of 2060 LDKTs were performed at Asan Medical Center, Seoul, Korea. After excluding HLA-incompatible transplantation, re-transplantation, and those without a clear history of childbirth, 390 female recipients were included and categorized into group I (offspring-to-mother, n=175), group II (husband-to-wife, n=159), and group III (unrelated, n=56). The primary endpoint was biopsy-proven acute rejection (BPAR) and graft survival. We also evaluated delayed graft function (DGF), death-censored graft failure, and mortality. RESULTS Group I had the lowest number of HLA mismatches (p<0.001), and group II had the highest number of ABO-incompatible transplantations (p=0.005). At 5 years after transplant, graft survival and death-censored graft survival did not significantly differ among the 3 groups (graft survival: 96.0% vs. 95.5% vs. 93.3%, p=0.685; death-censored graft survival: 98.3% vs. 97.5% vs. 100%, p=0.732). Five-year BPAR-free survival showed no significant differences among the 3 groups (88.6 vs. 88.7 vs. 88.6%, p=0.842). Group II had the highest rate of clinical rejection (p=0.103) and DGF (p=0.174), but the difference was not statistically significant. CONCLUSIONS Female LDKT recipients with possible pregnancy-related pre-sensitization who received grafts from offspring or husbands did not show significantly worse clinical outcomes than those who received grafts from unrelated donors.