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Purpose: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right‑lobe living donor liver transplantation (LDLT)., Methods and Results: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group., Conclusion: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor's round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: The consensus that portal venous pressure modulation, including splenectomy (Spx), prevents portal hypertension-related complications after living-donor liver transplantation (LDLT) has been established. However, little evidence about the risk factors for graft loss after simultaneous Spx during LDLT is available. This study aimed to identify the independent predictors of graft loss after simultaneous Spx during LDLT., Methods: Data of 655 recipients who underwent LDLT between 1997 and 2021 were collected and separated into the simultaneous Spx group (n = 461) and no-Spx group (n = 194)., Results: The simultaneous Spx group had significantly lower serum total bilirubin levels, drained ascites volumes, and prothrombin time-international normalized ratios on postoperative day 14 than the no-Spx group ( P  < 0.001 for each). Incidences of small-for-size graft syndrome ( P  < 0.001), acute cellular rejection ( P  = 0.002), and sepsis ( P  = 0.007) were significantly lower in the Spx group. Graft survival of the Spx group was significantly better than that of the no-Spx group ( P  < 0.001; hazard ratio [HR], 1.788; 95% confidence interval, 1.214-2.431). A multivariate analysis revealed that 3 variables, platelet count ≤4.0 × 10 4 /mm 3 ( P  = 0.029; HR, 2.873), donor age ≥60 y old ( P  = 0.013; HR, 6.693), and portal venous pressure at closure ≥20 mm Hg ( P  = 0.010; HR, 3.891), were independent predictors of graft loss within 6 mo after simultaneous Spx during LDLT., Conclusions: Spx is a safe inflow modulation procedure with a positive impact on both postoperative complications and prognosis for most patients. However, patients with the 3 aforementioned independent factors could experience graft loss after LDLT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria., Methods: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging., Results: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging., Conclusion: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT., Methods: We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss., Results: The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P = .067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P = .12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P = .034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P = .43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P = .038)., Conclusion: Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2 nd - and 3 rd -dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients., Methods: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls., Result: The median time were 21 days (between 1 st and 2 nd vaccination) and 244 days (between 2 nd and 3 rd vaccination). The median neutralizing antibody titer after 2 nd -dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2 nd -dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3 rd -dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups., Conclusion: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tomiyama, Suzuki, Harada, Tamura, Toshida, Kosai-Fujimoto, Tomino, Yoshiya, Nagao, Takeishi, Itoh, Kobayashi, Ito, Yoshio, Kanto, Yoshizumi and Fukuhara.)

Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The proportion of gastroduodenal ulcers caused by drugs is increasing. However, the risk of gastroduodenal ulcer from drugs other than nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin is unclear. An association between immunosuppressive drugs and gastroduodenal ulcers has been suggested. We aimed to identify the immunosuppressive drugs and clinical characteristics associated with gastroduodenal ulcers in post-liver transplant patients., Methods: The study investigated 119 patients who underwent esophagogastroduodenoscopy after liver transplantation, and 2 patients were excluded. Clinical characteristics, medications, and endoscopic images were retrospectively reviewed., Results: Among 117 post-living donor liver transplant recipients, gastroduodenal ulcers were found in 10 (9.2%) patients. The ulcer group had endoscopic gastritis more frequently (40%) compared with the non-ulcer group (10%). Logistic regression analysis revealed gastritis, NSAID use, and mycophenolate mofetil were risk factors in the post-liver transplant patients. Among 103 patients not on NSAIDs, 8 (7.8%) had peptic ulcer. The most common ulcer site and ulcer shape were the gastric antrum and a circular shape, respectively. All patients in the ulcer group were taking mycophenolate mofetil, which was the only immunosuppressive drug that showed a significant difference between the two groups. Five out of 8 ulcer patients (63%) were taking gastric acid suppressants, and gastroduodenal ulcers in post-liver transplant recipients were suggested to be refractory., Conclusion: Patients treated with immunosuppressive drugs after liver transplantation can develop gastroduodenal ulcers, even with gastric acid suppressant medication. Mycophenolate mofetil may increase the risk of gastroduodenal ulcers compared with other immunosuppressive drugs., (© 2023 S. Karger AG, Basel.)

The recipient muscle status is closely associated with postoperative poor survival in recipients of living donor liver transplantation (LDLT). However, it is uncertain whether LDLT donor muscle quality and quantity affect graft quality. Hence, we analyzed the correlation between donor muscle status and graft function. We measured the skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) of 380 LDLT donors. We examined the correlation between donor SMI or IMAC and graft mortality, the occurrence rates of small-for-size graft (SFSG) syndrome, and 6-month graft survival rates. The donor SMI had no effect on the occurrence of SFSG syndrome and graft survival, while a high IMAC in both male and female donors was significantly correlated with the rate of SFSG syndrome [high vs low: (male donors) 15.8% vs. 2.5%, p = 0.0003; (female donors) 12.8% vs. 3.1%, p = 0.0234] and 6-month graft survival rates [(male donors) 87.7% vs 95.9%, p = 0.02; (female donors) 83.0% vs. 99.0%, p < 0.0001]. Multivariate analysis revealed that a high donor IMAC (HR; 5.42, CI; 2.13-13.8, p = 0.0004) was an independent risk factor for 6-month graft survival, and the donor IMAC is useful for donor selection for high-risk recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tomiyama, Harada, Toshima, Nakayama, Toshida, Morinaga, Kosai-Fujimoto, Tomino, Kurihara, Takeishi, Nagao, Morita, Itoh and Yoshizumi.)

BACKGROUND Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. MATERIAL AND METHODS This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. RESULTS Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. CONCLUSIONS Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease., (Copyright © 2022. Published by Elsevier Inc.)

The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08-9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Aim: Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT., Methods: We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively., Results: Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%)., Conclusion: Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). Our goal was to evaluate prognostic impact of VETC in patients who underwent living-donor liver transplantation (LDLT) for HCC, focusing on the involvement of VETC with immune status in tumor microenvironment (TME)., Methods: Using a database of 150 patients who underwent LDLT for HCC, immunohistochemical staining of CD34 for VETC, angiopoietin-2 (Ang-2), CD3, and CD68, was reviewed with patients' clinicopathological factors., Results: A strong correlation between VETC pattern and malignant potential in HCC was observed; larger tumor size (P < 0.001), more numbers of tumors (P = 0.003), higher α-fetoprotein levels (P = 0.001), higher des-γ-carboxy prothrombin levels (P = 0.022), microvascular invasion (P < 0.001), and poor differentiation (P = 0.010). Overall survival (OS) of patients with VETC (+) was significantly lower than those with VETC (-) (P = 0.021; 5-year OS rates, 72.0% vs. 87.1%). Furthermore, the ratio of CD3 (+) cells was significantly lower in VETC (+) group (P = 0.001), indicating that VETC activity may be strongly correlated with lymphocyte activity. Moreover, combination status of VETC (+) /CD3 low was an independent risk factor for mortality (hazard ratio 2.760, 95% confidence interval 1.183-6.439, P = 0.019). Additionally, the combination of VETC expression with immune status (low CD3 levels) enabled further classification of patients based on their clinical outcome., Conclusions: Our results show the prognostic impact of VETC expression, tumor-infiltrating lymphocytes (TILs), and their combination in the setting of LDLT for HCC, which can be a novel prognostic biomarker for mortality after LDLT., (© 2021. Society of Surgical Oncology.)

Intrahepatic recipient hepatic artery dissection caused by hepatic artery thrombosis is a lethal complication of living-liver donor liver transplantation (LDLT). We herein report a new surgical technique that avoids the ligation of the recipient hepatic arteries in LDLT. Patients undergoing LDLT between 2009 and 2019 were evaluated. In the second half of this period, a technique involving no ligation of the recipient hepatic artery was initiated and its impact on the incidence of intrahepatic recipient hepatic artery dissection was determined. The middle and left hepatic arteries were ligated in 195 cases (53.4%), and the no-ligation technique was used in 170 (46.6%). The incidence of intraoperative hepatic artery dissection was significantly lower in the no-ligation group (n = 0, 0.0%) than in the ligation group (n = 10, 5.1%) (p = 0.0021). After propensity score matching to evaluate the patient characteristics, the incidence of intraoperative hepatic artery dissection was also significantly lower in the no-ligation group (n = 0, 0.0%) than in the ligation group (n = 6, 4.5%) (p = 0.0295). As a result, this new surgical technique is highly recommended to avoid recipient hepatic artery ligation in LDLT., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: Hepatopulmonary syndrome frequently complicates end-stage liver disease. It causes hypoxemia and requires oxygen administration. Additionally, interstitial pneumonia causes hypoxemia; however, it is known to be aggravated by high-concentration oxygen administration., Case Presentation: A 71-year-old woman with hepatopulmonary syndrome and interstitial pneumonia underwent living donor liver transplantation, requiring conflicting management in terms of the inspiratory oxygen concentration. We achieved a low intraoperative fraction of inspiratory oxygen by increasing the cardiac output with intravenous catecholamines. As a result, the transplanted liver functioned well postoperatively, and the patient was discharged without exacerbation of the interstitial pneumonia., Conclusion: We suggest that patients with hepatopulmonary syndrome complicated with interstitial pneumonia can undergo successful living donor liver transplantation without the use of high inspiratory oxygen concentration by using catecholamines to maintain a high mixed venous oxygen saturation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There are some reported cases of liver transplant between identical twins with no immunosuppressants because of their matched HLA. However, there is no mention of donor-specific antibodies (DSA). Here, we report a rare case of living donor liver transplant (LDLT) between identical twins, mimicking DSA positivity, on a low-dose immunosuppression protocol. A 57-year-old man with acute liver failure underwent LDLT using the right lobe from his identical twin. Their blood types were identical on HLA matching. However, the preoperative DSA test results were positive for class II antibodies. This was supposed to be due to the relatively large amount of blood transfusion before testing: a total of 580 units of fresh frozen plasma for plasma exchange. The presence of class II antibodies for DSA positivity was the result of the passive immunity from transfusion, and this result could not be ignored, given the risk of rejection. Therefore, we arranged low-dose postoperative immunosuppressants using tacrolimus at a quarter dose and no mycophenolate mofetil. The postoperative course was uneventful. A few months after LDLT, the patient's DSA level was negative for class II antibodies, thus confirming our preoperative hypothesis of DSA as the result of transfusion. Currently, 6 months after LDLT, he is free from immunosuppressive medication with good liver function. When administering relatively large doses of fresh frozen plasma by repeated plasma exchange before LDLT, even between identical twins, it is important to consider that the DSA test could be positive and that immunosuppressive treatment should be performed carefully., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Prolonged stay in an intensive/high care unit (ICU/HCU) after living donor liver transplantation (LDLT) is a significant event with possible mortality., Methods: Adult-to-adult LDLTs (n = 283) were included in this study. Univariate and multivariate analyses were performed for the factors attributed to the prolonged ICU/HCU stay after LDLT., Results: Recipients who stayed in the ICU/HCU 9 days or longer were defined as the prolonged group. The prolonged group was older (P = .0010), had a higher model for end-stage liver disease scores (P < .0001), and had higher proportions of patients with preoperative hospitalization (P < .0001). Delirium (P < .0001), pulmonary complications (P < .0001), sepsis (P < .0001), reintubation or tracheostomy (P < .0001), relaparotomy due to bleeding (P = .0015) or other causes (P < .0001), and graft dysfunction (P < .0001) were associated with prolonged ICU/HCU stay. Only sepsis (P = .015) and graft dysfunction (P = .019) were associated with in-hospital mortality among patients with prolonged ICU/HCU stay or graft loss within 9 days of surgery. Among these patients, grafts from donors aged <42 years and with a graft-to-recipient weight ratio of >0.76% had significantly higher graft survival than grafts from others (P = .0013 and P < .0001, respectively)., Conclusion: Prolonged ICU/HCU stay after LDLT was associated with worse short-term outcomes. The use of grafts of sufficient volume from younger donors might improve graft survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Biliary stricture (BS) is a severe complication after liver transplantation. It is difficult to treat, especially after living donor liver transplantation (LDLT). We successfully treated 4 patients for intractable BS after LDLT. All patients had developed cholangitis with stenosis of bile ducts anastomosis. CASE 1: . A 65-year-old woman underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Internal plastic stents inserted by endoscopic retrograde cholangiography (ERC) were changed quarterly for the next 2 years. CASE 2: A 55-year-old man underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Insertion of internal plastic stents by ERC was attempted; however, the posterior bile duct branch showed complete obstruction. After percutaneous transhepatic biliary drainage (PTCD), the stents were inserted using the rendezvous technique of ERC and were changed by ERC quarterly for the next 3 years. CASE 3: A 22-year-old man underwent LDLT with left lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and stents were changed quarterly for the next 2 years. CASE 4: A 60-year-old man underwent LDLT with right lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and changed to a metallic stent after 1 year. Three months later the stent was extracted using the rendezvous technique of double balloon enteroscopy., Conclusion: BS of complete obstruction type after LDLT is difficult to treat. Appropriate procedures should be chosen based on the types of strictures and biliary reconstruction methods., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT., Methods: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group)., Results: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT., Conclusions: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT., Lay Summary: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (<5000 steps/day) was 36%. Logistic regression analysis showed that postoperative hypertension and obesity were associated with preoperative body mass index and the number of steps taken (in 2000 steps/day increments). Preoperative diabetes was associated with obesity, and PA was associated with physical function-related HRQOL scores. Thus, increasing the number of steps taken per day has the potential to reduce hypertension and obesity, and PA could improve physical function-related HRQOL in patients following LT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aims of this study were to: (a) describe the physical activity (PA) and quality of life (QOL) in living donor liver transplant (LDLT) recipients pre-operatively and at 3 months and 6 months post-operatively; (b) compare PA and QOL at 6 months post-operatively with a healthy control group; and (c) explore pre-operative factors that predict PA changes., Methods: Patients over 20 years of age who were undergoing LDLT were recruited. PA was measured based on the number of steps/day and time spent performing moderate-to-vigorous PA (MVPA) during 1 week using an accelerometer. QOL was assessed based on a physical (PCS) and mental (MCS) component summary of the eight-item Short-Form Health Survey. The LDLT and healthy control groups were matched for age (±3 years) and gender. Pre-operative factors predicting a change in PA were calculated using a generalized linear mixed model., Results: Twenty-four patients completed the study. By 6 months post-LDLT, the MCS and PCS were comparable to those in the control group. The number of steps (3,887 steps/day) and MVPA (29.3 min/week) showed significant improvement by 6 months post-operatively, but remained much lower compared with those in the control group. The multivariate analysis showed that younger age (p < .01, p = .04) and higher skeletal muscle mass (SMM; p < .01, p = .03) were predictors of improvement in number of steps and MVPA., Conclusion: This study suggests the need for pre-operative interventions by healthcare professionals that focus on outcomes such as improving low SMM to facilitate post-operative PA recovery., (© 2020 Japan Academy of Nursing Science.)

Objectives: The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil capsules as part of induction therapy after living-donor liver transplant., Materials and Methods: Between July 2017 and April 2019, we retrospectively enrolled 20 adult primary living-donor liver transplant recipients. Recipients were divided into 3 groups: group 1 received mycophenolate mofetil suspension of 3000 mg (n = 6), group 2 received 3000 mg mycophenolate mofetil via opened capsules (n = 8), and group 3 received mycophenolate mofetil suspension of 2000 mg (n = 6). Administration was started on postoperative day 1, with tacrolimus administered on postoperative day 2 or day 3., Results: The values of area under the plasma concentration time curve for 0 to 12 hours were significantly higher in the 3000 mg/day mycophenolate mofetil suspension group than in the 2000 mg/day mycophenolate mofetil suspension group (P = .024) and in the 3000mg/day mycophenolate mofetil capsule group (P = .013). Significant positive correlations were shown between blood concentration at 8 hours after administration and the plasma concentration time curve for 0 to 12 hours (r2 = 0.96; P < .001) in patients in the suspension group. No patients required mycophenolate mofetil reduction because of leukopenia and diarrhea. Only 1 biopsy-proven acute cellular rejection was recognized in the mycophenolate mofetil suspension group (at 2000 mg/day). There were no significant differences in frequency of opportunistic infections among the 3 groups., Conclusions: Mycophenolate mofetil suspension is useful as part of immunosuppressive induction therapy after living-donor liver transplant because its concentration increases greater than that of mycophenolate mofetil capsules and because of the low risk of rejection and adverse events.

Introduction: The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe., Materials and Methods: Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n = 123), one arterial stump with left hepatic artery reconstruction; Group B (n = 32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n = 61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups., Results: No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT., Conclusions: Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Metabolic syndrome (MS) is the most common long-term complication after liver transplantation, and it has been increasing in incidence. The aim of this study was to clarify the risk factors for each MS component -hypertension, diabetes mellitus, and dyslipidemia-after living-donor liver transplantation (LDLT), including characteristics of living-donors., Methods: Data related to clinicopathological parameters including MS components in 461 consecutive patients who underwent LDLT were analyzed retrospectively., Results: Prevalence of all MS components (hypertension, diabetes mellitus, and dyslipidemia) increased from 9.3%, 16.5%, and 7.2% before LDLT to 44.9%, 45.3%, and 50.8% after LDLT, respectively. By multivariate logistic regression analysis, the three factors, cyclosporine use (OR 2.086, P = 0.001), recipient age (OR 1.036, P = 0.001), and BMI (OR 1.072, P = 0.026) were independent predictors for post-LDLT hypertension. Next, the three factors, male recipient (OR 2.471, P < 0.001), recipient age (OR 1.039, P = 0.002), and donor BMI (OR 1.124, P = 0.012) were independent for post-LDLT diabetes mellitus. The four factors, cyclosporine use (OR 2.015, P = 0.001), prolonged prednisolone use (OR 1.928, P = 0.002), recipient age (OR 1.019, P = 0.037), and GRWR (OR 0.316, P = 0.037) were independent for post-LDLT dyslipidemia as well., Conclusions: Not only recipient-related factors but also donor-related factors were independently associated with each targeted post-LDLT MS component., (Copyright © 2019. Published by Elsevier Ltd.)

Extrahepatic malignancy is a relative contraindication for liver transplant in many countries. Nevertheless, the indications for living-donor liver transplantation (LDLT) for such patients vary by institution. Our aim was to reevaluate the indications for LDLT in patients with extrahepatic malignancy. We retrospectively reviewed data for 609 patients who underwent adult LDLT from May 1997 to January 2018 and analyzed patients with a history of extrahepatic malignancies or concurrent malignancies. Fourteen patients had extrahepatic malignancies concurrent with or before LDLT. Malignancies in 9 patients were detected during their systematic screening for LDLT. The mean duration between surgeries was 70 days (range, 20-209 days). Five patients had a history of extrahepatic malignancies before considering LDLT. The estimated 5-year survival rate was 100%. Although the risk and long-term prognosis of patients with extrahepatic malignancy are not well known, such patients can be candidates for LDLT if they undergo curative surgery for the malignancy, and if the prognosis of the malignancy is the same or superior to that of LDLT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is well known that the CYP3A5*3 polymorphism is an important marker that correlates with the tacrolimus dose requirement after organ transplantation. Recently, it has been revealed that the POR*28 polymorphism affects the pharmacokinetics of tacrolimus in renal transplant patients. In this study, we examined whether POR*28 as well as CYP3A5*3 polymorphism in Japanese recipients and donors would be another biomarker for the variation of tacrolimus blood levels in the recipients during the first month after living-donor liver transplantation. We enrolled 65 patients treated with tacrolimus, who underwent liver transplantation between July 2016 and January 2019. Genomic DNA was extracted from whole-blood samples, and genotyping was performed to examine the presence of CYP3A5*3 and POR*28 polymorphisms in the recipients and donors. The CYP3A5*3/*3 genotype (defective CYP3A5) of the recipient (standard partial regression coefficient [median C/D ratio of CYP3A5 expressor vs. CYP3A5 non-expressor, p value]: Pod 1-7, β= -0.389 [1.76 vs. 2.73, p < 0.001]; Pod 8-14, β = -0.345 [2.03 vs. 2.83, p < 0.001]; Pod 15-21, β= -0.417 [1.75 vs. 2.94, p < 0.001]; Pod 22-28, β = -0.627 [1.55 vs. 2.90, p < 0.001]) rather than donor (Pod 1-7, β = n/a [1.88 vs. 2.76]; Pod 8-14, β = n/a [1.99 vs. 2.93]; Pod 15-21, β = -0.175 [1.91 vs. 2.94, p = 0.004]; Pod 22-28, β = n/a [1.61 vs. 2.67]) significantly contributed to the increase in the concentration/dose (C/D) ratio of tacrolimus for at least one month after surgery. We found that the tacrolimus C/D ratio significantly decreased from the third week after transplantation when the recipient carried both CYP3A5*1 (functional CYP3A5) and POR*28 ( n = 19 [29.2%], median C/D ratio [inter quartile range] = 1.58 [1.39-2.17]), compared with that in the recipients carrying CYP3A5*1 and POR*1/*1 ( n = 8 [12.3%], median C/D ratio [inter quartile range] = 2.23 [2.05-3.06]) ( p < 0.001). In conclusion, to our knowledge, this is the first report suggesting that the POR*28 polymorphism is another biomarker for the tacrolimus oral dosage after liver transplantation in patients carrying CYP3A5 * 1 rather than CYP3A5 *3/ *3 ., Competing Interests: The authors declare no conflict of interest.

Background: Hepatic artery occlusion (HAO) is a life-threatening complication after liver transplantation. We report a case of portal vein arterialization (PVA) with anastomosis of the recipient common hepatic artery (CHA) and a graft of the round ligament to achieve intrahepatic arterial flow., Case Presentation: A 57-year-old man had a medical history of decompensated liver cirrhosis secondary to cholestatic liver disease owing to biliary anastomotic stricture after living donor liver transplantation and end-stage renal failure. He underwent deceased donor liver and renal transplantation with anastomosis of the recipient proper hepatic artery and the graft CHA. He experience symptoms from HAO on postoperative day 23 and underwent emergency surgery to re-anastomose the hepatic artery. Despite several instances of re-anastomoses, intrahepatic arterial flow was not able to be achieved and therefore PVA with anastomosis of the recipient CHA and the graft round ligament was performed. Although liver enzyme levels rapidly declined after surgery and the finding of liver infarction was not observed, a large amount of watery stool was observed owing to portal hypertension, which was an adverse effect of PVA. As enhanced computed tomography on POD 31 showed a pseudoaneurysm of the anastomotic site, occlusion with coils was performed to arrest hemorrhage, and a contrast study after coil occlusion showed intrahepatic arterial blood flow via collateral arteries. Thereafter, the patient needed treatment for ischemic biliary duct stenosis and was discharged home on POD 98., Conclusion: PVA using a round ligament for HAO after liver transplantation might play a role as a bridge treatment until retransplantation or maturation of collaterals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Idiopathic copper toxicosis (ICT) is characterized by marked copper deposition, Mallory-Denk body (MDB) formation and severe hepatic injury. Although the characteristics are apparently different from Wilson disease, large amounts of copper accumulate in the liver of the patients. We extensively treated a patient with ICT to reduce the body copper, however, the patient needed liver transplantation. Previous liver biopsy revealed high copper content. But extirpated liver contained an extremely small amount of copper, although MDBs and severe inflammation remained. These phenomena suggest abnormal copper metabolism is not the principle cause of ICT but some other abnormality must exist.

Background: Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers., Methods: Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed., Results: The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746)., Conclusions: Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients.

Management of portal vein thrombosis (PVT), especially advanced PVT involving the superior mesenteric vein (SMV), in living donor liver transplantation (LDLT) is challenging. There were 514 adults who underwent LDLT between 2005 and 2018 included in this retrospective study, and PVT was observed in 67 (13.0%) patients. The LDLT recipients with PVT were characterized by increased portal pressure at laparotomy (26.1 ± 6.0 versus 24.3 ± 5.9 mm Hg; P = 0.03) and at closure (16.8 ± 3.9 versus 15.6 ± 3.6 mm Hg; P = 0.02), increased operative blood loss (14.6 ± 29.7 versus 5.7 ± 6.3 L; P < 0.01), and decreased 1-year graft survival (83.5% versus 92.8%; P = 0.04). Among the 18 patients with atrophic or vanished portal vein on pre-LDLT computed tomography, significant portal atrophy was actually observed only in 1 (5.6%) patient during LDLT surgery. For advanced PVT (n = 7) involving SMV in era 1, we performed nonanatomical inflow reconstruction using interposition grafts, resulting in significant inflow problems in 4 (57.1%) patients. Thus, for the patients with advanced PVT (n = 4) in era 2, we abandoned nonanatomical reconstruction and applied extensive thrombectomy under ultrasound guidance with secure shunt ligation, resulting in no inflow problems and no graft loss. In conclusion, even for advanced PVT involving SMV, extensive thrombectomy under sonogram guidance followed by anatomical inflow reconstruction and shunt ligation is a legitimate strategy in adult LDLT with PVT., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL); however, the mechanism of its development has yet to be uncovered. A few ATL cases have been reported in HTLV-1-positive recipients after living donor liver transplantation. A 57-year-old HTLV-1-positive Japanese male suffered acute liver failure due to hepatitis B infection. He was transferred to our department to undergo deceased donor liver transplantation (DDLT). Tacrolimus and mycophenolate mofetil were induced for immunosuppression. His clinical outcome was satisfactory. However, he visited his physician 3 years after DDLT reporting abdominal pain and fever. A computed tomography scan showed multiple lymph node enlargement. Lymph node biopsy and his blood sample led to a diagnosis of ATL. He was transferred to the Department of Hematology and Oncology and underwent chemotherapy. To our knowledge, this is the first report of ATL development after DDLT from an HTLV-1-positive recipient. As is the case with our previous report, the current patient had undergone liver transplant for acute liver failure. Unlike living donor liver transplantation, however, DDLT needs no hepatic growth factor for liver regeneration. This finding sheds light on the resolution of the mechanism for the development of ATL from the HTLV-1 carrier., (Copyright © 2019. Published by Elsevier Inc.)

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI ( n = 6) than in those who did not ( n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended.

Cholangitis is a major complication following transplantation. We report a living donor liver transplant (LDLT) patient with cholangitis due to multiple stones in the intrahepatic bile duct during hepaticojejunostomy anastomosis, who was successfully treated with the rendezvous technique using double balloon endoscope. A 64-year-old woman underwent LDLT with right lobe graft and hepaticojejunostomy for Wilson disease. There was bile leakage with biliary peritonitis, which was treated conservatively after transplant. Two years after surgery, she developed reiterated cholangitis due to stenosis of hepaticojejunostomy anastomosis and multiple stones in the intrahepatic bile ducts. Percutaneous transhepatic biliary drainage was performed. The size of the drainage tube was increased, and the anastomotic area was dilated in a stepwise manner using a balloon catheter. The stones were crushed and lithotomy was performed using electronic hydraulic lithotripsy through cholangioscopy. Finally, lithotomy was performed for the remaining stones through endoscopic retrograde cholangiography with the rendezvous technique using the double balloon endoscope. Rendezvous approach with percutaneous transhepatic biliary drainage and double balloon endoscopic retrograde cholangiography was an effective treatment for the multiple intrahepatic stones in hepaticojejunostomy following LDLT with right lobe graft., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate the effect of hepatic artery (HA) size mismatch anastomosis on outcomes after living-donor liver transplantation (LDLT)., Materials and Methods: After excluding 128 patients with the exclusion criteria among 233 LDLTs using the right lobe, 104 LDLT patients were divided into two groups: donor HA diameter that was greater than or equal to the recipient HA diameter (D ≥ R group; n = 79), and donor HA diameter that was smaller than the recipient HA diameter (D < R group; n = 25)., Results: Hepatic artery-related complications occurred in only one patient (HA thrombosis; 1.0%) who was in the D < R group. The reconstructed HA flow in the D ≥ R group was significantly greater than that in the D < R group (P = 0.015). There was a higher incidence of anastomotic biliary stricture in the D < R group (32.0%) compared with the D ≥ R group (13.9%, P = 0.022) after LDLT. A multivariate analysis with Cox regression revealed that the HA anastomosis of the D < R group and hepaticojejunostomy were significant independent risk factors for postoperative anastomotic biliary stenosis., Conclusions: Hepatic artery anastomosis with a donor HA diameter smaller than that of the recipient HA might be an independent risk factor for postoperative biliary stenosis after LDLT using the right lobe., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Thrombectomy is a routine or common practice for treating organized portal vein thrombosis (PVT) during liver transplantation. However, this procedure is often performed in a blinded fashion and can result in insufficient thrombectomy or devastating consequences such as injury to the retropancreatic portal vein where prompt repair is very difficult. To overcome these drawbacks for blind thrombectomy, we herein describe a new technique that makes complex thrombectomy safe and easy under direct ultrasound vision. This procedure is readily available and highly reproducible and can be used as the standard procedure for treating extensive PVT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment., (© 2018 by the American Association for the Study of Liver Diseases.)

Background/aim: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD., Patients and Methods: Fifty healthy donors for liver transplantation underwent CT. BMD was measured as cross-sectional average pixel density (Hounsfield units) only in trabecular-bone at Th11 bottom. Validation was performed on another 50 healthy donors to check the accuracy of formulae for standard BMD., Results: Measured BMD was significantly correlated with age in both males and females (p<0.0001). The formulae to calculate standard BMD were 308.82-2.49 × Age in males and 311.84-2.41 × Age in females. Estimated BMD was significantly correlated with measured BMD in males and females (p<0.0001)., Conclusion: Osteopenia can be defined by the difference between measured data and calculated data using our new formula based on each age., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT)., Methods: We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT., Results: Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045)., Conclusions: Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality.

Background/aim: This study's aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir., Patients and Methods: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated., Results: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy., Conclusion: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Liver transplantation has been established as the optimal treatment for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also effective in patients with well-preserved liver function. Determining the suitable surgical treatment for patients with Child-Pugh class B cirrhosis is a more difficult challenge., Methods: We retrospectively compared the results of hepatic resection and living donor liver transplantation for hepatocellular carcinoma in 137 patients with Child-Pugh class B cirrhosis. The procedures were performed at Kyushu University Hospital from April 2014 through October 2016., Results: Patients who underwent hepatic resection were significantly older and had better liver function, larger tumor size, smaller number of tumors, and less surgical stress compared with patients who underwent living donor liver transplantation. The overall survival rate and the recurrence-free survival rate in patients with transplantation were significantly better than that in patients with resection. The multivariate analysis showed that recurrent hepatocellular carcinoma and microvascular invasion were significant prognostic factors for both overall and recurrence-free survival in the hepatic resection group. In the group with protein induced by vitamin K absence or antagonist-II ≥300 mAU/mL, both the overall survival curve and the recurrence-free survival curve in patients with living donor liver transplantation were not significantly different from those in patients with hepatic resection., Conclusions: Living donor liver transplantation for hepatocellular carcinoma in patients with Child-Pugh class B cirrhosis was favorable under the condition of protein induced by vitamin K absence or antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection for recurrent hepatocellular carcinoma and excessive blood loss should be avoided in patients with Child-Pugh class B cirrhosis.