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Background: The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Methods: Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. Results: There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). Conclusions: Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations. [ABSTRACT FROM AUTHOR]

Abstract Background The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Methods Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. Results There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P

Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

The incidence of hepatocellular carcinoma (HCC) is increasing, despite effective antiviral treatment for hepatitis B (HBV) and C virus infection and the application of preventive measures such as vaccination at birth against HBV infection. This is mainly due to the increase in metabolic syndrome and its hepatic components, nonalcoholic fatty liver disease and steatohepatitis. Liver resection and transplantation are the main treatment options, offering long-term survival and potential cure. In this review, the recent advances in the surgical management of HCC are presented. More specifically, the role of liver resection in the intermediate and advanced stages, according to the Barcelona Clinic Liver Cancer classification, is analyzed. In addition, the roles of minimally invasive surgery and of living-related liver transplantation in the management of patients with HCC are discussed. Finally, recent data on the role of molecular markers in the early diagnosis and recurrence of HCC are presented. The management of HCC is complex, as there are several options for each stage of the disease. In order for, each patient to get the maximum benefit, an individualized approach is suggested, in specialized liver units, where cases are discussed in multidisciplinary tumor boards. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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<0.0001). Conclusions: LDLT is a lifesaving procedure for pediatric patients with ALF. Our experience showed that it may be performed with very good results, and with very low morbidity and no mortality among living donors when performed by experienced teams following strict procedures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Most liver transplant recipients receive calcineurin inhibitors (CNIs), especially tacrolimus and cyclosporine, as immunosuppressant agents to prevent rejection. A controversy exists as to whether the outcomes of hepatitis C virus (HCV)-infected liver transplant patients differ based on the CNIs used. This meta-analysis compares the clinical outcomes of tacrolimus-based and cyclosporine-based immunosuppression, especially cases of HCV recurrence in liver transplant patients with end-stage liver disease caused by HCV infection. Methods: Related articles were identified from the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, and Embase. Meta-analyses were performed for the results of homogeneous studies. Results: Nine randomized or quasi-randomized controlled trials were included. The total effect size of mortality (RR = 0.98, 95% CI: 0.77–1.25, P = 0.87) and graft loss (RR = 1.05, 95% CI: 0.83–1.33, P = 0.67) showed no significant difference between the two groups irrespective of duration of immunosuppressant therapy after liver transplantation. In addition, the HCV recurrence-induced mortality (RR = 1.11, 95% CI: 0.66–1.89, P = 0.69), graft loss (RR = 1.62, 95% CI: 0.64–4.07, P  = 0.31) and retransplantation (RR = 1.40, 95% CI: 0.48–4.09, P = 0.54), as well as available biopsies, confirmed that histological HCV recurrences (RR =  0.92, 95% CI: 0.71–1.19, P = 0.51) were similar. Conclusion: These results suggested no difference in posttransplant HCV recurrence-induced mortality, graft loss and retransplantation, as well as histological HCV recurrence in patients treated with tacrolimus-based and cyclosporine-based immunosuppresion. [ABSTRACT FROM AUTHOR]

Background. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a novel, sensitive and specific biomarker that is rapidly released after kidney injury. It predicts acute kidney injury (AKI) in multiple clinical scenarios. We hypothesized that urinary NGAL can predict AKI after liver transplantation.Methods. Urine was collected in 92 patients undergoing liver transplantation (18 living-related and 74 deceased) before surgery, after reperfusion of the liver graft and then 3, 18 and 24 h later. NGAL was analyzed with enzyme-linked immunosorbent assay and corrected for dilution/concentration by calculating urinary NGAL/urine creatinine ratios. AKI was defined by Risk-Injury-Failure-Loss-Endstage stage kidney disease (RIFLE)-risk criteria (increase of serum creatinine by >50%).Results. Urinary NGAL/urine creatinine ratio was low prior to surgery and increased immediately after reperfusion, peaked 3 h later and remained elevated at 18 and 24 h. Urinary NGAL/urine creatinine ratios were higher in patients with post-operative (post-OP) AKI defined by RIFLE––risk criteria 3 and 18 h after reperfusion. The area under the curve of the receiver operator characteristics curve of urinary NGAL/urine creatinine ratio to predict AKI was 0.800 (95% CI: 0.732–0.869, P < 0.0001) 3 h and 0.636 (95% CI: 0.551–0.720, P < 0.005) 18 h after reperfusion.Conclusions. We conclude that urinary NGAL/urine creatinine ratio is able to predict post-OP AKI 3 and 18 h after transplantation with good discrimination. [ABSTRACT FROM AUTHOR]

Despite advances in patient selection, surgical technique, immunosuppression, and peri-operative management, the need for liver replacement exceeds organ availability. Moreover, in Italy, where the overall rate of cadaver donation is 21 donors per million per year, there are areas of the country, such as Sicily, where the rate of cadaver donation is 9.3 donors per million per year. In fact, this ongoing shortage of organs has led surgeons to develop innovative techniques in an attempt to expand the donor pool, and clinicians are continually modifying criteria to accept organs, particularly the previously defined expanded or marginal donor organs, which are now defined as extended criteria donor. Rarely, in certain specific settings alternative strategies based on the appropriate donor-recipient match allowed the use of grafts that otherwise would have been discarded due to anatomic anomalies. The organ shortage becomes more problematic in the scenario of re-transplantation where the use of a limited resource such as a liver graft must be weighed against the risk of a more difficult surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: Although living-related liver transplantation (LRLT) is effective for patients with biliary atresia (BA) after a failed Kasai operation, the pretransplant factors affecting post-LRLT mortality and the optimal timing of the procedure remain unclear. Method: A retrospective review of 27 patients with BA after a failed Kasai operation (median age, 22 months; range, 6-237 months) who received LRLT from 1994 to 2005 was done. The clinical characteristics at the time of the pre-LRLT assessment of those who did and did not survive were compared. A simple regression analysis and receiver operating characteristic analysis were done to correlate the clinical data. Results: Among the 27 patients, 4 patients died within 1 year post-LRLT. The significant factors affecting posttransplant death were hepatopulmonary syndrome (HPS), age at LRLT, and graft-to-recipient weight ratio. The arterial blood gas analysis of HPS patients showed that there was a significant negative correlation between the Sao 2 value on room air and the intrapulmonary shunt ratio. The receiver operating characteristic analysis of age at LRLT showed that the optimal cutoff point was 103 months of age. Conclusion: Older children with HPS or a lower graft-to-recipient weight ratio are not ideal candidates for LRLT. The correlation between the shunt ratio and Sao 2 suggests that HPS could be detected early using pulse oximetry. [Copyright &y& Elsevier]

The portal hyperperfusion, or small-for-size syndrome (SFSS), is a widely recognized clinical complication that may occur after segmental liver transplantation. Several surgical strategies have been proposed to reduce portal blood inflow and portal pressure after partial liver transplantation. In particular, splenic artery ligation and splenectomy have been used without a firm hemodynamic basis for these procedures. Our group recently demonstrated that, in patients with cirrhosis and portal hypertension, the occlusion of the splenic artery causes a significant reduction in the portal pressure gradient, which is directly related to the spleen volume and indirectly related to the liver volume. This concept is at the center of our strategy for performing early splenic artery embolization (SAE) for the treatment of SFSS after living-related liver transplantation (LRLT). Six patients developed small-for-size syndrome, defined as: onset within the first week after LRLT of progressive hyperbilirubinemia without mechanical cause; marked cholestasis; centrilobular sinusoidal dilatation and hepatocyte atrophy at liver biopsy; and refractory ascites in the absence of vascular complications. All six patients who underwent SAE rapidly improved their clinical condition, with an evident decrease in the value of bilirubin in the serum, in the production of ascites, and improvement in condition of pancytopenia. Coagulopathy expressed by the international normalized ratio value (INR) was not a reliable early marker of SFSS in this series; in fact a slight improvement in the result of this test was already present immediately after LRLT and before SAE. Because splenic flow clearly contributes to portal hyperperfsion, an early SAE can relieve the partial graft from the deleterious effect of this portal overflow. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Living-related liver transplantation has become the treatment of choice for many liver diseases. We present our initial analysis of 53 cases of adult to adult living-related liver transplantation performed in a single institute in Italy. Materials and methods: From January 2002 to September 2006, we performed 53 adult to adult living-related liver transplantations. The donors (age 18–53) all had genetic or emotional relationships; they were all ABO identical or compatible. Recipients (ages 18–68) suffered from cirrhosis secondary to viral etiology (18), hepatocellular carcinoma with viral cirrhosis (24), cystic fibrosis (2), primary biliary cirrhosis (2), hepatocellular carcinoma with non-viral cirrhosis (2), alcoholic cirrhosis (1), ornithine transcarbamylase deficiency (OTC), (1) criptogenic cryptogenic cirrhosis, (1) primary sclerosing cholangitis, (1) biliary atresia and metastatic carcinoid (1). Donor liver resection resulted in 51 right hepatectomies and two left hepatectomies. Graft body weight ratio was always above 0.8%; graft implantation was performed with the piggy back technique and, in 43 cases, with the use of veno-venous bypass. Results: There was neither donor mortality nor need of blood transfusion. Actuarial recipient survival rate at 3 years was 82.66% and graft survival rate was 75.34%. Six patients underwent retransplantation: in four cases due to hepatic artery thrombosis, and in two, due to graft dysfunction. Three patients had one episode each of acute cellular rejection. Conclusion: Adult to adult living-related liver transplantation represents a resource to be used in confronting organ shortage, and is a valuable option for decreasing mortality and drop out from the waiting list. [Copyright &y& Elsevier]

Background: Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We investigated whether exogenous application of T3 improves liver regeneration after 70% partial hepatectomy (PH) and confers a survival advantage after 90% subtotal hepatectomy (SH) in rats and whether this is associated with the stimulation of angiogenesis. Methods: Rats were subjected to PH or SH 10 days after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic proliferation (Ki-67), biochemical markers as well as vascular endothelial growth factor (VEGF) expression were assessed by immunohistochemistry. Gene expression of pathogenic relevant genes was determined by customized cDNA arrays and quantitative RT-PCR. Results: T3-treated rats showed an increased LBR and Ki-67 index after PH and SH, which reached statistical significance compared to placebo-treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an increased expression of VEGF as demonstrated by immunohistochemistry, which was associated with a higher expression of its receptor Flt-1. Conclusions: Exogenous administration of T3 ameliorates liver regeneration after 70% PH and 90% SH, possibly due to stimulation of angiogenesis. Therefore, its clinical use might be of interest due to its excellent general practicability. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Progressive familial intrahepatic cholestasis (PFIC) is a severe cholestatic liver disease of early life often requiring liver transplantation. Organ shortage leads to consider living-related liver transplantation. Because of possible partial metabolic defect in heterozygotes, the use of familial donors might be questionable. We therefore evaluated the safety of this procedure, for both donors and recipients. We compared a series of seven parental–children pairs, having participated in the living related liver transplant program for PFIC between 1994 and 2001, with that of a series of seven parental–children pairs, performed for biliary atresia (BA) during the same period. No primary graft dysfunction was observed. There was no difference in the course of transaminases, γ-glutamyl transpeptidase and bilirubin levels after transplantation in both donor and recipient series. Thirteen recipients and 14 donors are alive and well 3–10 yr post-surgery. One PFIC recipient died nine months post-orthotopic liver transplantation from sepsis. We conclude that PFIC heterozygote status of the donor does not increase the risk of liver dysfunction in either recipients or donors, with a similar course compared with BA recipients and donors. [ABSTRACT FROM AUTHOR]

We report a case of a two-yr-old boy with hepatoblastoma resectable only by total hepatectomy including the vena cava. Successful LTx was performed with a living donor segment without vena cava reconstruction. The tumor was located in the bilateral lobe, surrounding the IVC. In spite of the high-dose chemotherapy, the tumor did not become resectable. LTx was performed using left lateral segment after removal of the IVC combined with total hepatectomy. Because the collaterals were well developed, the patient tolerated the procedure well. The serum AFP level decreased from 186 699 to 8 ng/mL in 11 months after LTx without local recurrence or distant metastasis. [ABSTRACT FROM AUTHOR]

Feasibility of duct-to-duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct-to-duct biliary reconstruction in children, the surgical outcomes of duct-to-duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end-stage liver disease in each of them was fulminant Wilson's disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct-to-duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post-operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow-up of 28 months. In conclusion, our results show that duct-to-duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx. [ABSTRACT FROM AUTHOR]

Serious intestinal bleeding from vascular ectasia secondary to extrahepatic portal thrombosis is much less frequent than variceal bleeding, and its treatment is not clearly defined. We describe a 4-year-old girl with repeated intestinal bleeding from vascular ectasia, without any varix, with late extrahepatic portal vein thrombosis (PVT) and late hepatic artery thrombosis (HAT) after living-related liver transplantation. The bleeding stopped after simple splenectomy. She has presented neither bleeding nor any serious complications related to splenectomy for 1 year to date. We think uncontrollable hemorrhage from gastrointestinal vascular ectasia secondary to extrahepatic portal thrombosis in a pediatric patient can and should be treated by simple splenectomy, because patients with this complication usually have a normally functioning liver. However, it is not clear whether this procedure is effective for variceal bleeding. [ABSTRACT FROM AUTHOR]

Orthotopic liver transplantation has been applied to the treatment of Wilson's disease (WD), living-related liver transplantation (LRLT) has also been indicated for WD with increasing frequency. Between January 2001 and November 2003, 22 LRLTs were performed on patients (19 pediatric, three adults) with WD in liver transplantation center. Two patients were transplanted because of a presentation coexistent with fulminant hepatic failure. Twenty presented with chronic advanced liver disease with ( n = 9) or without ( n = 11) associated neurologic manifestations. All the recipients had low serum ceruloplasmin levels with a mean value of 12.8 ± 3.2 mg/dl before transplantation and increased to an average of 26.0 ± 3.6 mg/dl after LRLT at the latest evaluation. The survival patients with neurologic manifestations such as tremor, dysarthia, dysphagia, dystonia and sialorrhea had improved after LRLT. This suggests that LRLT not only resolves the hepatic but also ameliorates the neurologic consequences of WD. [ABSTRACT FROM AUTHOR]

Although an accurate anatomical understanding of the hepatic arteries is the most and essential step in living-related liver transplantation (LRLT), the need to reduce the burden place on the donor should be considered in imaging diagnosis. The present study examined the reliability of intravenously enhanced three-dimensional (3D) angiography from multidetector-row computed tomography (MDCT) in evaluating the anatomical configuration of the hepatic arteries comparing with those from conventional angiography by Seldinger method. A total of 109 patients underwent MDCT and 3D images were reconstructed on arterial phase using the volume rendering (VR) method. In the case of 3D angiography, at an infusion rate of 4 ml/s, the extrahepatic hepatic arteries were visualized successfully in all cases (the right, left and middle hepatic artery). The aberrant hepatic arteries were successfully visualized in 23 of 24 cases. The 3D angiography is a reliable method of visualizing the extrahepatic and aberrant hepatic arteries. This minimally invasive examination procedure is useful in individual operative planning and is help to increase the safety of surgery. [ABSTRACT FROM AUTHOR]

Kimura T, Hasegawa T, Sasaki T, Shimizu Y, Mushiake S, Fukuzawa M, Okada A. Optimal timing for living related liver transplantation in children. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00194.x © Blackwell Munksgaard, 2004 The pediatric end stage liver disease (PELD) score has been used widely to prioritize children awaiting cadaveric liver transplantation (LTx). To establish the objective parameter for optimal timing of living-related LTx (LRLTx), we have assessed our cases using the PELD score. From 1997 to 2002, 24 children were evaluated 28 times for the indication of LRLTx. Among them, 15 were for jaundice and nine for growth failure, hepatopulmonary syndrome, and variceal bleeding. Nine of 24 children underwent LRLTx. They were divided into several groups according to their clinical course. The PELD score consisted of age, albumin, total bilirubin, prothrombine time-international ratio (INR) and growth failure. A cut-off value was obtained by the highest positive and negative predictive value. The PELD score in cases whose indication for LRLTx was approved was significantly higher compared with the cases who were not, and a cut-off value of 4 was obtained. The PELD score in cases who were alive after LRLTx was significantly lower compared with the cases who died after LRLTx or evaluation of the indication, and a cut-off value of 22 was established. LRLTx may be considered when the PELD score exceeds 4, and LRLTx may be required immediately when the PELD score exceeds 22. [ABSTRACT FROM AUTHOR]

Background CT-assisted volumetry permits an estimation of the volume of the graft in liver transplantation, as well as monitoring the donor's liver regeneration. The aim of the study was to observe the restitution of liver tissue in donors after harvesting of the liver fragment for living-related liver transplantation (LRLT). Methods The size of the whole liver and of segments II, III and IV was assessed by preoperative CT volumetry in 29 living-related liver donors. Segments II and III were harvested in 22 patients, segments II, III and IV in 6 patients. The remnant liver was assessed by CT volumetry on the 7th and 30th postoperative days. Results The correlation between the calculated volume of the graft and its weight was linear ( r = 0.56, p < 0.04). Postoperative CT volumetry of the liver of living-related donors showed a different pattern of volume restoration (regeneration index) at both 7 and 30 days between donors who sacrificed segments II and III and those who sacrificed segments II, III and IV. The mean regeneration indexes were significantly higher in donors of segments II, III and IV as compared with donors of segments II and III (7 days, p < 0.02; 30 days, p < 0.05). Discussion It is possible that the donor's liver displays a different pattern of growth due to the alteration in blood supply to segment IV. [ABSTRACT FROM AUTHOR]

Abstract: Acute cellular rejection (ACR) and preservation injury (PI) are major complications occurring early after liver transplantation (LTx) and sometimes lead to severe graft dysfunction. We herein report an infant who developed marked hyperbilirubinemia as a result of combined ACR and PI in addition to ischemic damage from bleeding, but recovered without re-LTx. In a 1-yr-old-girl undergoing living-related LTx, liver biopsy (LBx) on post-operative day 7 showed ballooning of the hepatocytes, i.e. microvesicular steatosis (30%) and occasional centrolobular necrosis, consistent with mild-to-moderate PI and ACR with a rejection activity index (RAI) of 2.0. Because drainage of an intra-abdominal abscess was performed and a systemic infection was considered severe, the tacrolimus level was decreased and steroids were discontinued. The total bilirubin level started to rise, thereafter, reaching a maximum of 47.6 mg/dL at 1 month after LTx. LBx showed an RAI of 6.0 and steatosis of 10%. With good response to an increase of tacrolimus level and administration of steroid, the total bilirubin level gradually decreased, finally reaching the normal range in 3 months, and LBx showed no steatosis or finding of ACR. From this experience, ACR, if combined with mild-to-moderate PI or other ischemic damage, may lead to severe clinical manifestations after LTx, which, however, could remit with conservative therapy and without re-LTx. [ABSTRACT FROM AUTHOR]

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III–IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological... [ABSTRACT FROM AUTHOR]

Patients with severe liver diseases, such as liver cirrhosis and biliary atresia, have low natural killer (NK) cell activity. The relations between NK activity and measures of liver function, including serum levels of total bilirubin, total bile acids, bile acid components, aspartate aminotransferase, and alanine aminotransferase, and platelet count were examined in patients with biliary atresia (6 boys and 6 girls; mean age, 4.8+/-5.7 years) and patients with liver cirrhosis due to hepatitis C virus infection (10 men and 2 women; mean age, 54.3+/-13.8 years). Univariate analysis showed that platelet count was positively correlated with NK activity in patients with biliary atresia (r = 0.611, P < 0.05). Serum levels of free chenodeoxycholic acid were negatively correlated with NK activity both in patients with biliary atresia (r = -0.647, P < 0.05) and in patients with hepatitis C virus-related liver cirrhosis (r = -0.876, P < 0.01). None of the other free bile acids or conjugated bile acids or other indicators of liver function were correlated with NK activity. Multiple stepwise regression analysis showed that only levels of free chenodeoxycholic acid were independently correlated with NK activity. All patients with biliary atresia underwent liver transplantation from living related donors. NK activity had increased significantly two months after transplantation (from 24.1+/-20.2% to 49.2+/-12.5%, P < 0.01). In contrast, levels of free chenodeoxycholic acid in transplant recipients had decreased significantly two months after transplantation (from 1.22+/-1.16 to 0.26+/-0.21 micromol/l, P < 0.05). In conclusion, in patients with biliary atresia or liver cirrhosis, NK activity in peripheral blood decreases, mostly because of free chenodeoxycholic acid. [ABSTRACT FROM AUTHOR]

We evaluate the portal venous waveform (PVW) with pulsed Doppler ultrasound (US) after living-related liver transplantation (LRLT) and correlate it with subsequent abnormalities. In the first 2 wk after LRLT, pulsed Doppler US demonstrated three types of PV waveform (PVW) in 33 recipients: non-phasic PVW in 19 patients, pulsatile in 10, and turbulent in 4. In the pulsatile PVW group, arterio-portal (A-P) shunt was confirmed in three grafts by either arteriograhy or computed tomography during hepatic arteriography. A severe stenosis in the grafted vein was confirmed in one case by both US and venography. The pulsatile PVW in the remaining six cases spontaneously disappeared and turned to the non-phasic PVW without treatment. The graft volume/liver standard volume (GV/SV) ratio was significantly smaller in the pulsatile PV waveform group than in the non-phasic PVW group (p<0.01). In the turbulent PVW group, aneurysmal-like dilatation of the portal vein at the umbilical portion was formed in 3 of the 4 patients. The pulsatile waveform in the PV is frequently observed with pulsed Doppler after LRLT, especially in patients that received small grafts. We should keep in mind that they often disappear without any treatment, although some examples of pulsatile waveforms represent vascular complications. [ABSTRACT FROM AUTHOR]

Background & Aims: The shortage of liver grafts continues to worsen. Because the expanded use of small-for-size grafts (SFSGs) would substantially alleviate this shortage, we aimed to analyse the available knowledge on auxiliary liver transplantation (ALT) with SFSGs in patients with chronic liver disease (CLD) to identify opportunities to develop ALT with SFSGs in patients with CLD., Methods: This is a systematic review on ALT using SFSGs in patients with CLD. The review was completed by updates obtained from the authors of the retained reports., Results: Heterotopic ALT was performed in 26 cases between 1980 and 2017, none for SFGS stricto sensu , and auxiliary partial orthotopic liver transplantation (APOLT) in 27 cases (from 1999 to 2021), all for SFSG. In APOLT cases, partial native liver resection was performed in most of cases, whereas the second-stage remnant native liver hepatectomy was performed in 9 cases only. The median graft-to-body weight ratio was 0.55, requiring perioperative or intraoperative portal modulation in 16 cases. At least 1 complication occurred in 24 patients following the transplant procedure (morbidity rate, 89%). Four patients (4/27, 15%) died after the APOLT procedure. At the long term, 19 (70%) patients were alive and well at 13 months to 24 years (median, 4.5 years) including 18 with the APOLT graft in place and 1 following retransplantation., Conclusions: Despite high postoperative morbidity, and highly reported technical variability, the APOLT technique is a promising technique to use SFSGs in patients with CLD, achieving satisfactory long-term results. The results need to be confirmed on a larger scale, and a standardised technique could lead to even better results., Lay Summary: At the cost of a high postoperative morbidity, the long-term results of APOLT for small-for-size grafts are good. Standardisation of the procedure and of portal modulation remain needed., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living-related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16-yr-old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patient's mother. In the recipient, the pre-transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post-transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c-met on the membrane of the hepatocytes were positive. TGF-β was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c-met was clearly detected on the cell membrane of the hepatocytes. Neither TGF-β nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non-parenchymal cells and c-met was positive in the cytoplasm of the hepatocytes. TGF-β was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF-β. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c-met system is thought to be involved in the mechanism of... [ABSTRACT FROM AUTHOR]

A 2 1/2-year-old girl underwent a living-related liver transplantation for biliary atresia, following which four percutaneous liver biopsies were performed uneventfully during her hospital stay for the evaluation of recurrent rejection. Her condition improved without any complications, and she was discharged from hospital in a stable condition on postoperative day (POD) 51. However, 3 months later she was readmitted with marked ascites and a moderate elevation of her liver function tests. A color Doppler ultrasound (US) confirmed hepatofugal portal blood flow, and selective celiac arteriography demonstrated an intrahepatic arterioportal (A-P) fistula. An attempt to embolize the fistula failed and a surgical approach was attempted without success. The patient died from irreversible liver failure on POD 152. A review of the previous histologic analyses revealed that arterial components were present in the fourth biopsy specimen; for this reason it was hypothesized that this procedure may have led to the development of the A-P fistula. [ABSTRACT FROM AUTHOR]

In view of the relative scarcity of pediatric cadaveric donors, living-related liver transplantation has recently been accepted as an alternative approach. It is also the only method of liver transplantation available in countries where cadaveric organ procurement is prohibited. Here we describe our experience of living-related liver transplantation in 17 patients at Shinshu University Hospital. The safety of the donor operation is of paramount importance in this type of liver transplantation. In Japan, retransplantation is very difficult in the event of the liver graft becoming nonfunctional. We have therefore placed emphasis on the donor hepatectomy technique as well as on surgical procedures and postoperative care to prevent graft loss in the recipient. Fifteen of the 17 patients who received liver transplants are currently alive; and 1 died of cytomegalovirus infection, and 1 of pulmonary complications. The actuarial 1-year survival rate for our series, determined by Kaplan-Meier analysis, was 89.5%. Although living-related liver transplantation requires a complicated surgical procedure, it has achieved reasonable results for both donors and recipients. We consider that living-related liver transplantation is a useful and reasonable option for patients requiring liver transplantation. [ABSTRACT FROM AUTHOR]