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BackgroundThis study investigated the association between the fibrinogen level and the risk of acute kidney injury (AKI) in patients who have undergone living donor liver transplantation (LDLT).Patients and methodsA total of 676 patients who underwent LDLT were analyzed retrospectively. Exclusion criteria included a history of severe kidney dysfunction, emergency operation, deceased donor, ABO-incompatible transplantation, and missing data. The study population was divided into low and normal fibrinogen groups. A 1:1 propensity score (PS) matching analysis was used to evaluate the association between a low fibrinogen level (< 160 mg/dL) and postoperative development of AKI.ResultsIn total, 142 patients (23.1%) developed AKI after LDLT. The PS matching analysis showed that the probability of AKI was two-fold higher in the low fibrinogen group than in the normal fibrinogen group. In addition, patients with AKI had poorer postoperative outcomes such as longer hospitalization, longer ICU stay, and higher mortality than patients without AKI.ConclusionsThe preoperative fibrinogen level may be useful for risk stratification of patients undergoing LDLT in terms postoperative development of AKI.

Introduction Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors. Methods Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results. Results Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016–1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively. Conclusion The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies.

Background Somatic tissue oxygen saturation (SstO2) is associated with systemic hypoperfusion. Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction. Patients and methods Data from 304 adults undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary’s Hospital were retrospectively collected. Thirty-six patients were excluded based on the exclusion criteria. In total, 268 adults were analyzed, and 200 patients were 1:1 propensity score (PS)-matched. Results Patients with early kidney dysfunction had significantly lower intraoperative SstO2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction. Conclusions Kidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.

Donor-Recipient (D-R) matching is one of the main challenges to be fulfilled nowadays. Due to the increasing number of recipients and the small amount of donors in liver transplantation, the allocation method is crucial. In this paper, to establish a fair comparison, the United Network for Organ Sharing database was used with 4 different end-points (3 months, and 1, 2 and 5 years), with a total of 39, 189 D-R pairs and 28 donor and recipient variables. Modelling techniques were divided into two groups: 1) classical statistical methods, including Logistic Regression (LR) and Naïve Bayes (NB), and 2) standard machine learning techniques, including Multilayer Perceptron (MLP), Random Forest (RF), Gradient Boosting (GB) or Support Vector Machines (SVM), among others. The methods were compared with standard scores, MELD, SOFT and BAR. For the 5-years end-point, LR (AUC = 0.654) outperformed several machine learning techniques, such as MLP (AUC = 0.599), GB (AUC = 0.600), SVM (AUC = 0.624) or RF (AUC = 0.644), among others. Moreover, LR also outperformed standard scores. The same pattern was reproduced for the others 3 end-points. Complex machine learning methods were not able to improve the performance of liver allocation, probably due to the implicit limitations associated to the collection process of the database.

It has been reported that donor age affects patient outcomes after liver transplantation, and that telomere length is associated with age. However, to our knowledge, the impact of donor age and donor liver telomere length in liver transplantation has not been well investigated. This study aimed to clarify the influence of the length of telomere and G-tail from donor livers on the outcomes of living donors and recipients after living donor liver transplantation. The length of telomere and G-tail derived from blood samples and liver tissues of 55 living donors, measured using the hybridization protection assay. The length of telomeres from blood samples was inversely correlated with ages, whereas G-tail length from blood samples and telomere and G-tail lengths from liver tissues were not correlated with ages. Age, telomere, and G-tail length from blood did not affect postoperative liver failure and early liver regeneration of donors. On the other hand, the longer the liver telomere, the poorer the liver regeneration tended to be, especially with significant difference in donor who underwent right hemihepatectomy. We found that the survival rate of recipients who received liver graft with longer telomeres was inferior to that of those who received liver graft with shorter ones. An elderly donor, longer liver telomere, and higher Model for End-Stage Liver Disease score were identified as independent risk factors for recipient survival after transplantation. In conclusion, telomere shortening in healthy liver does not correlate with age, whereas longer liver telomeres negatively influence donor liver regeneration and recipient survival after living donor liver transplantation. These results can direct future studies and investigations on telomere shortening in the clinical and experimental transplant setting.

Objectives Living donor liver transplantation (LDLT) in patients with acute liver failure (ALF) has become an acceptable alternative to transplantation from deceased donors (DDLT). The aim of this study was to analyze outcomes of LDLT in pediatric patients with ALF based on our center’s experience. Material and methods We enrolled 63 children (at our institution) with ALF who underwent liver transplantation between 1997 and 2016. Among them 24 (38%) underwent a LDLT and 39 (62%) received a DDLT. Retrospectively analyzed patient clinical data included: time lapse between qualification for transplantation and transplant surgery, graft characteristics, postoperative complications, long-term results post-transplantation, and living donor morbidity. Overall, we have made a comparison of clinical results between LDLT and DDLT groups. Results Follow-up periods ranged from 12 to 182 months (median 109 months) for LDLT patients and 12 to 183 months (median 72 months) for DDLT patients. The median waiting time for a transplant was shorter in LDLT group than in DDLT group. There was not a single case of primary non-function (PNF) in the LDLT group and 20 out of 24 patients (83.3%) had good early graft function; 3 patients (12.5%) in the LDLT group died within 2 months of transplantation but there was no late mortality. In comparison, 4 out of 39 patients (10.2%) had PNF in DDLT group while 20 patients (51.2%) had good early graft function; 8 patients (20.5%) died early within 2 months and 2 patients (5.1%) died late after transplantation. The LDLT group had a shorter cold ischemia time (CIT) of 4 hours in comparison to 9.2 hours in the DDLT group (p

Background Patients with end-stage liver disease frequently experience acute kidney injury (AKI) after living donor liver transplantation (LDLT). Serum levels of brain natriuretic peptide (BNP) have increasingly been accepted as a predictor of AKI in clinical settings. This study investigated the predictive role of intraoperative BNP levels in the early development of AKI after LDLT. Patients and methods Adult patients (≥19 years old) who had undergone elective LDLT from January 2011 to December 2017 were classified into the non-AKI and AKI groups according to the Kidney Disease: Improving Global Outcomes criteria. Serum levels of BNP were measured three times in the preanhepatic, anhepatic, and neohepatic phases. Perioperative data in recipients and donors were analyzed retrospectively. Results Sixty-one patients (22.4%) suffered from AKI immediately after LDLT. Severity according to AKI stage was as follows: 28 patients in stage 1 (10.3%), 18 patients in stage 2 (6.6%), and 15 patients in stage 3 (5.5%). In the neohepatic phase, both BNP levels and proportions of patients with high BNP levels (≥100 pg/mL) were higher in the AKI group than in the non-AKI group. Only BNP levels in the non-AKI and AKI stage 1 groups significantly decreased from the preanhepatic phase to the neohepatic phase; those in AKI stages 2 and 3 groups did not. In particular, BNP levels of all AKI stage 3 patients increased to more than 100 pg/mL, and the proportion of patients with high levels also increased significantly through the surgical phases in the AKI stage 3 group. In multivariate analyses, BNP levels in the neohepatic phase were significantly associated with early development of AKI after LDLT, as well as the total amount of packed red blood cells in transfusions and total duration of graft ischemia. Conclusions Monitoring serum levels of BNP is useful for predicting the early development of AKI after LDLT.

Background Prolongation of corrected QT interval (QTc) on the electrocardiogram is associated with cardiac arrhythmia and sudden death. Changes in the QTc (corrected QT) interval before and after liver transplantation (LT) for the treatment of liver cirrhosis (LC) and its association with clinical outcomes have not been fully evaluated. Methods From January 2011 to May 2016, consecutive 516 consecutive recipients were enrolled into LT registry and the median follow-up was 31 months (IQR 12–52). Patients with an available electrocardiogram before LT and 1 month after from LT were analyzed. Patients were divided into 2 groups according to prolonged QTc interval. The patient groups were analyzed separately according whether the electrocardiogram was preoperative or postoperative. The primary outcome was all-cause death during the follow-up period. Results A total of 283 patients were enrolled in the study. In the preoperative QTc prolongation group, there was not a significant rate difference in all-cause mortality in multivariate analysis (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.53–1.66; P = 0.26). However, in the postoperative QTc prolongation group, mortality was significantly increased (HR, 1.78; 95%CI, 1.05–3.03; P = 0.03) in patients who underwent LT. Conclusion In patients who underwent LT for LC, postoperative QTc prolongation on ECG, rather than preoperative, is associated with mortality. Larger clinical trials are needed to support this finding.

Objective To evaluate the predictive role of the Model for End-Stage Liver Disease (MELD) score concerning changes in testosterone levels following living donor liver transplantation (LDLT) and the effects of LDLT on total testosterone and sex hormone-binding globulin (SHBG) levels, the free androgen index (FAI) and erectile function in LDLT recipients. Participants 41 adult male recipients of LDLT were evaluated before transplantation and six months after LDLT. Main outcome measures We evaluated the effects of LDLT on total testosterone and SHBG levels, the FAI and erectile function in LDLT recipients. In this prospective study, MELD score, serum total testosterone, SHBG levels and FAI were measured in the morning of the operation day and 1 month, 3 months and 6 months after LDLT. The 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire was administered before LDLT and six months after LDLT to evaluate erectile function. Results The main outcome measure was dynamic parameter changes of total testosterone, SHBG, FAI and erectile dysfunction. The mean FAI value before LDLT was 16.75±10.10. The mean FAI was significantly higher 1 month (32.75±15.56; p < 0.01), 3 months (25.23±10.26; p < 0.01) and 6 months (29.16±11.05; p < 0.01) after LDLT. Mean IIEF-5 scores significantly increased after LDLT (from 11.7±7.7 before LDLT to 14.7±7.5, p< 0.01). Conclusions MELD score correlates with severity of hypogonadism in men with end-stage liver disease. LDLT results in a reduction in serum levels of SHBG, an increase in FAI and improvement in erectile function.

Background In India, annually, 500,000 people die due to non-availability of organs. Given the large proportion of brain death amongst road accident victims, any improvement in organ donation practices amongst this cohort could potentially address this deficit. In this study, we identify the potential areas for intervention to improve organ donation amongst professional drivers, a population more likely to suffer from road accidents. Methods 300 participants were surveyed using a structured, orally-administered questionnaire to assess knowledge, attitudes and practices regarding organ donation. Multivariate analysis was performed to identify key variables affecting intent to practice. Results Nearly half our participants had unsatisfactory knowledge and attitude scores. Knowledge and attitude was positively correlated, rs (298) = .247, p < .001, with better scores associated with a higher likelihood of intent to practice organ donation [AOR: 2.23 (1.26–3.94), p = .006; AOR: 12.164 (6.85–21.59), p < .001 respectively]. Lack of family support and fear of donated organs going into medical research were the key barriers for the same [AOR: 0.43 (0.19–0.97), p = .04; AOR: 0.27 (0.09–0.85), p = .02 respectively]. Conclusion Targeted health-education, behaviour change communication, and legal interventions, in conjunction, are key to improving organ donor registrations.

Background In Western countries, most patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). The number of patients with UC in East Asia has increased markedly over the past two decades. However, current clinical features of PSC and of PSC associated with UC (PSC-UC) have not yet been clarified in East Asia, particularly in Japan. We aimed to reveal the clinical courses and associations with UC in Japanese patients with PSC from the mutual viewpoint of PSC and UC. Methods We retrospectively retrieved medical records of patients with PSC (69) and UC (1242) who were diagnosed at Chiba University Hospital between June 1991 and August 2017. Results In the present cohort, 37 patients had PSC-UC; the cumulative risks of PSC in patients with UC and of UC in patients with PSC were 3.0% and 53.6%, respectively. We confirmed similar distinctive results by a Japanese nationwide survey, noting that younger patients with PSC had a notably high possibility of association with UC. From the viewpoint of the UC cohort, the occurrence of right-sided disease was significantly higher in patients with PSC-UC than in those with UC (16.2% vs. 4.2%, P = 0.003). Pancolitis was more commonly observed in PSC-UC, and proctits/left-sided colitis was less commonly found in patients with UC. The number of patients with young-onset PSC-UC may be increasing similar to an increase in patients with UC in Japan. Conclusions In our cohort, the comorbidity rate of PSC-UC was higher than that obtained in previous reports. The incidence of PSC-UC and UC may increase in the future in East Asia, particularly in Japan.

Background Intrapulmonary thermodilution technique using a pulmonary artery catheter is widely used for measuring cardiac output (CO) in patients undergoing liver transplantation. However, its invasiveness and associated complications have led to an interest in less invasive modalities. Thus, we aimed to evaluate whether the new calibrated pulse-wave analysis method monitoring (VolumeViewTM/EV1000TM) is interchangeable with intrapulmonary thermodilution technique. Methods Twenty-eight patients undergoing living donor liver transplantation were enrolled in this prospective observational study. COs were recorded automatically by the two devices and compared simultaneously at 10-minute intervals. The agreement of absolute CO values and the tracking ability of CO changes trends were compared. A Bland-Altman analysis with percentage errors and concordance rate for trend analysis using both a 4-quadrant plot and a polar plot were performed on the data. Results A total of 375 paired datasets from 25 patients were included in analysis. COs measured by intrapulmonary thermodilution ranged from 3.8–13.7 L/min. The mean CO difference between the two techniques was 0.57 L/min, and the 95% limits of agreement were -0.98 L/min to 2.12 L/min with a percentage error of 42.3%. The percentage errors in the dissection, anhepatic, and reperfusion phase were 30.5%, 31.7%, and 27.4%, respectively. The concordance rate between the two techniques was 78.4%. Conclusion The calibrated pulse-wave analysis and intrapulmonary thermodilution failed to show acceptable interchangeability in terms of both estimating CO and tracking CO changes during living donor liver transplantation.

To investigate the effect of IL28B single nucleotide polymorphisms (SNPs) (rs8099917 and rs12979860) in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT). The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD) and post-operative day 30 (POD30). There was a significant difference in HCV-RNA clearance before (12%, 6/50) and after (48%, 24/50) liver transplantation (P < 0.001). The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50) and donors (86%, 43/50), but had no significant effect on HCV-RNA clearance (87.5%, 21/24) and recurrence (76.9%, 20/26) after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient) and 92% (46/50 donor) and prevalence of genotype CC was 2% (1/50 recipient) and 8% (4/50 donor) on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24) exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26), however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further.

Background Liver graft regeneration is orchestrated by specific and sequential stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We evaluated the association between preoperative serum cytokines and early liver graft regeneration in human living donor liver transplantation (LDLT). Patients and methods We retrospectively reviewed the data of adult patients who underwent LDLT from January 2010 to December 2014. Serum cytokines, including interleukin (IL)-2, 6, 10, 12, 17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured in the recipients 1 day before surgery and on postoperative day (POD) 7. Liver graft volume was estimated using abdominal computed tomography images of the donors and recipients. Results In total, 226 patients were analyzed in this study. Median preoperative levels of serum cytokines were as follows: IL-2, 0.1 (0.1–1.6) pg/mL; IL-6, 7.3 (0.1–30.2) pg/mL; IL-10, 0.5 (0.1–11.0) pg/mL; IL-12, 0.1 (0.1–0.1) pg/mL; IL-17, 2.0 (0.1–16.4) pg/mL; IFN-γ, 3.2 (0.1–16.0) pg/mL; and TNF-α, 9.8 (5.4–17.9) pg/mL. Higher preoperative serum levels of IL-6, IL-10, and TNF-α, dichotomized at the median, were associated with increased relative liver volumes by POD 7. Multivariate analysis revealed that higher levels of serum IL-6 and TNF-α were independently associated with increased graft volume during the first 1 week after LDLT, based on the lower levels of those cytokines. Conclusions IL-6 and TNF-α were important mediators of the success of early graft regeneration in patients who underwent LDLT.

Background The decision to become a living liver donor is a stressful event. Ambivalence in decision making may result in psychological distress. Thus, the purpose of this study was to provide a description of the ambivalence of potential living liver donors, to examine the predictors of ambivalence, and to compare the ambivalence of potential living liver donors with that of actual living liver donors. Methods This descriptive and correlational study was conducted in a medical center from August 2013 to December 2015. Self-reported questionnaires were used to collect data. A total of 263 potential living liver donors who were assessed for donation to their parents were included in this study. Results The mean age of the total sample was 30.7 years (SD = 6.39, range = 20–47), and males comprised 53.6% of the sample. The majority of the potential donors had a college education (70.8%) and were single (63.5%). Of the total sample, the mean score for ambivalence was 4.27 (SD = 1.87, range = 0–7). Multivariate analysis revealed that the Mental Component Summary (MCS) of quality of life (β = -0.24, p < 0.01), family support (β = -0.17, p = 0.007), and intimacy (β = -0.13, p = 0.04) were significant protective predictors of ambivalence. Actual living liver donors had significantly lower ambivalence (3.82 versus 4.60), higher intimacy with recipients (3.55 versus 3.34), higher MCS (45.26 versus 42.80), and higher family support (34.39 versus 29.79) than did the remaining potential living liver donors. Conclusion Ambivalence is common in potential living liver donors. The MCS of quality of life, family support, and intimacy were protective predictors in terms of ambivalence. Future research should explore other factors and design interventions targeted toward reducing ambivalence, promoting family support, and enhancing the mental dimensions of quality of life in potential living liver donors.

Background The reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival. Methods Recipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted. Results Early reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7–96.4), and 85.2% (95%CI, 66.5–94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0–98.2), and 92.9% (95%CI, 85.0–96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9–99.5), and 88.3% (95%CI, 69.3–96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7–94.3) and 88.0% (95%CI, 79.2–93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59). Conclusions Observed graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.