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Background: Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation., Methods: We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height., Results: Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were -2.26, -1.59, -0.91, and -0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became -0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor., Conclusions: Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although chronic kidney disease (CKD) after liver transplantation (LTx) is a common complication in adults, its long-term significance after pediatric LTx remains unclear. We examined the decades-long transition of renal function and revealed the risk factors for late-onset CKD after pediatric LTx in a single-center retrospective cohort of 117 pediatric LTx recipients who survived >5 y., Methods: The estimated glomerular filtration rate (eGFR) and CKD stages were calculated using serum creatinine. Risk factor analysis for late-onset CKD was performed in 41 patients whose eGFR could be evaluated at >20 y after LTx., Results: The median age at LTx was 1.3 y, and most primary diagnoses were biliary atresia (77%). The mean pre-LTx and 1, 5, 10, 20, and >20 y post-LTx eGFRs were 180, 135, 131, 121, 106, and 95 mL/min/1.73 m 2 , respectively, with a median renal follow-up period of 15 y. The eGFR declined by 47% at >20 y after LTx ( P  < 0.001). CKD was observed in 8%, 19%, and 39% of cases at 10, 20, and >20 y after LTx, respectively. In patients receiving cyclosporine, trough levels were 1.5 times higher in those with CKD up to 10 y after LTx. The multivariate analysis showed that older age at LTx (odds ratio, 1.3 by 1 y; P  = 0.008) and episodes of repeated/refractory rejection (odds ratio, 16.2; P  = 0.002) were independent risk factors of CKD >20 y after LTx., Conclusions: In conclusion, renal function deteriorates slowly yet steadily after pediatric LTx. Long-term careful surveillance is essential after pediatric LTx, especially in repeated/refractory rejection or long-term high trough-level use of cyclosporine cases., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Various formulae have been used for the estimation of standard liver volume (SLV) in preparation for living donor liver transplantation (LDLT). However, these formulae have the disadvantage of being constructed using parameters that are substantially affected by the patient's condition. Here, we aimed to establish more precise formulae that are less affected by the general condition of the patient., Methods: We analyzed the liver volumes of LDLT donors and patients with normal livers (total: n = 213) using the SYNAPSE VINCENT imaging analysis system, to develop new formulae. The accuracy of the new formulae were compared with those of existing formulae in a separate validation group of healthy patients (n = 200). The new formulae were also validated using 81 LDLT recipients to assess their utility for graft selection in LDLT., Results: Body surface area (BSA) and skeletal muscle mass index (SMI) independently affected total liver volume (TLV). We produced new formulae for SLV incorporating SMI: SLV = 32.2 × L3-SMI-466.9 for men, with R2 .92, and 25.7 × L3-SMI-55.97 for women, with R2 .79 (alongside a BSA formula with R2 .57), which provided the most accurate predictions of TLV in the validation group. A graft volume (GV)/SLV <.35, calculated using the new formulae, predicted the postoperative prognosis, including the development of small-for-size syndrome, sepsis, or acute rejection, significantly more effectively than GV/SLV using the previous formulae., Conclusions: The newly developed L3-SMI-based formula is more accurate for the estimation of SLV than previously reported formulae, and may thus help to improve the safety of LDLT., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Since the first success in an adult patient, living donor liver transplantation (LDLT) has become an universally used procedure. Small-for-size syndrome (SFSS) is a well-known complication after partial LT, especially in cases of adult-to-adult LDLT. The definition of SFSS slightly varies among transplant physicians. The use of a partial liver graft has risks of SFSS development. Persistent portal vein (PV) hypertension and PV hyper-perfusion after LT were identified as the main factors. Hence, various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome. Herein, the definition, clinical symptoms, pathophysiology, basic research, as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences., Data Sources: The articles were collected through PubMed using search terms "liver transplantation", "living donor liver transplantation", "living liver donation", "partial graft", "small-for-size graft", "small-for-size syndrome", "graft volume", "remnant liver", "standard liver volume", "graft to recipient body weight ratio", "sarcopenia", "porcine", "swine", and "rat". English publications published before March 31, 2020 were included in this review., Results: Many transplant surgeons performed PV flow modulation, including portocaval shunt, splenic artery ligation and splenectomy. With these techniques, patient outcome has been improved even when using a "small" graft. Other factors, such as preoperative recipients' nutritional and skeletal muscle status, graft congestion, and donor factors, were also identified as risk factors which all have been addressed using various strategies., Conclusions: The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients. In the absence of efficacious medications to resolve SFSS, conservative treatments, including aggressive fluid balance correction for massive ascites, anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy, are all required if SFSS could not be prevented., (Copyright © 2020. Published by Elsevier B.V.)

A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.

To introduce duct-to-duct biliary anastomosis to conventional temporary auxiliary partial orthotopic liver transplantation (APOLT) using living donor graft for patients with familial amyloid polyneuropathy, we modified the conventional APOLT procedure in a manner characterized by the use of the recipient's common hepatic duct for biliary reconstruction and the preservation of the right posterior section alone for the certain placement of a tube into the corresponding biliary tree for external biliary drainage (modified APOLT). This procedure was performed in 3 patients without biliary complications. No complications associated with the external drainage tube occurred. Here we report the techniques and results for this new procedure., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Aims: Recurrent hepatitis is a significant complication after liver transplantation for hepatitis C virus (HCV) disease. To evaluate responsiveness to treatment of HCV disease after liver transplantation, in situ hybridisation (ISH) was employed., Methods: Sense and anti-sense probes for HCV were synthesised, and ISH studies were performed on 19 liver biopsy specimens from 19 recipients who had undergone living donor liver transplantation for HCV disease. ISH positive cells and total hepatocytes were counted, and the percentage of positive cells was calculated. Other clinical findings were compared retrospectively with the ISH results., Results: The subjects were divided into three groups: recurrent HCV hepatitis (RHC, n = 11), acute cellular rejection (ACR, n = 5), and recurrent HCV hepatitis with ACR (MIX, n = 3). The percentage of ISH positive cells was almost the same degree (10-20%) in the three groups. The RHC group was subdivided into two sets of patients in whom serum HCV titres decreased (group D, n = 7) or did not decrease (group ND, n = 3) after 1 month of IFN therapy. The percentage of ISH positive cells in group D was significantly lower than that in group ND (p < 0.05), Conclusions: ISH for the recipients with HCV may be useful for predicting the response to interferon therapy.

Biliary complications remain a significant cause of morbidity following living donor liver transplantation. The purpose of this retrospective study was to assess the outcome of nonsurgical management for hepatojejunostomy stricture in our institution. We reviewed 22 patients with hepatojejunostomy stricture among the 231 patients who underwent living donor liver transplantation between June 1990 and December 2005. Hepatojejunostomy stricture was confirmed by percutaneous transhepatic or endoscopic retrograde cholangiography. Anastomotic strictures were treated by balloon dilatation. Percutaneous transhepatic cholangiography was performed on 15 of the 22 patients. Two of 15 patients, with complete obstruction of the anastomosis, were treated successfully by Yamanouchi magnet compression anastomosis. Although another two patients died of infectious disease that was unlikely to have been related to biliary complications, anastomotic patency was maintained in the other 13 patients. Endoscopic retrograde cholangiography was performed on seven of the 22 patients. None of the 22 patients required re-operation or died of biliary complications. The 5-year graft survival rate of 85.6% in the 22 patients with stricture was equivalent to that of the patients without stricture (82.9%, P = 0.98). Advances in intervention techniques have enabled wider application of nonsurgical approaches for this complication, and fair results have been obtained.

Background/purpose: This study was carried out to investigate the risk factors contributing to hepatic artery thrombosis in living-donor liver transplantation., Methods: Two hundred and twenty-two recipients (113 adults and 109 children) of living-donor liver transplantation were the subjects of this study. The diagnosis of hepatic artery thrombosis was made by color-Doppler ultrasonography and/or hepatic angiography. Parameters for this study were: (1) donor sex, age, and body weight; (2) recipient sex, age, body weight, liver disease, preoperative prothrombin time, and type of arterial reconstruction; and (3) previous liver transplantation., Results: Hepatic artery thrombosis occurred in 12 patients (5.4%) at 3 to 15 days posttransplant. Recipient female sex and metabolic disorder as the original disease were found to be significantly associated with hepatic artery thrombosis. The 5-year patient survival rate in recipients with hepatic artery thrombosis (58.3%) was significantly lower than that in recipients without this complication (84.4%)., Conclusions: Female sex and metabolic disease may be factors contributing to hepatic artery thrombosis after living-donor liver transplantation. More intensive anticoagulation therapy for this patient population might decrease the incidence of hepatic artery thrombosis and, thus, posttransplant recipient mortality.

Background: A major prerequisite for living donor liver transplantation (LDLT) as an acceptable treatment modality is thoughtful consideration of the donor. However, there has been no comprehensive audit of living liver donation focusing on issues such as donor selection, anatomic surveys, and long-term outcome., Methods: Between June 1990 and January 2002 at our institution, 160 LDLTs were performed and 177 patients were referred for LDLT. For these patients, a total of 203 potential donors were screened. The process of donor selection, safety of donor hepatectomy, and postoperative morbidity were investigated. Additionally, an anonymous questionnaire was administered to 100 donors who had undergone LDLT more than 3 years previously., Results: Thirty-eight (19%) of the 203 donor candidates were excluded. Precise estimation of the hepatic anatomy was indispensable for donor safety. None of the donors showed prolonged postoperative liver dysfunction nor developed complications requiring reoperation or readmission. There was no donor mortality. The responses to the questionnaire indicated that 95% of the living donors had not felt coerced to donate and that 5% were neutral about coercion pressure. There were no severe postoperative aftereffects, but minor problems were reported by 51% of the respondents., Conclusions: Our appraisal of the perioperative and long-term postoperative course of LDLT donors revealed that although most donors are satisfied after undergoing LDLT, there is a need for strict attention to the process of donor selection and long-term postoperative follow-up. The outcome of the present series seems to confirm the safety of donor hepatectomy.

Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.

Background: In liver transplant patients with hypoplastic portal vein (PV), when the narrowed segment is extended too deep into the dorsal side of the pancreas, it is difficult and dangerous to reconstruct the interposition graft from the upper part of the pancreas. Herein, we present a case of PV reconstruction with the autologous mesosystemic shunt vessel from the caudal side of the pancreas in a situation where the narrowed PV was deep, and we discuss the technical details. Case presentation: A 25-year-old woman presented with cholestatic liver cirrhosis due to biliary atresia after Kasai procedure. Since her jaundice progressed, she was referred to our hospital for liver transplantation. Laboratory tests showed that her total bilirubin was elevated to 7.6 mg/dL. The Model for End-Stage Liver Disease score was 18, and the Child–Pugh score was 9 (Grade B). She underwent living donor liver transplantation (LDLT) using a right hemi-liver graft procured from her 54-year-old mother. The conventional approach from the cephalad side to the superior mesenteric vein (SMV) and splenic vein (SpV) confluence behind the pancreas was extremely difficult in this case because the confluence of SMV and SpV was close to the lower edge of the pancreas. Therefore, we decided to perform PV reconstruction from the caudal side. The main trunk of PV was documented as narrow (5 mm in diameter), for which retro-pancreatic pull-through PV reconstruction was successfully performed using her own mesosystemic shunt vessel. A contrast computed tomography (CT) scan was performed on postoperative day 5 because of an elevation of D-dimer and found a partial thrombus in the left pulmonary artery, as well as in the PV and left renal vein. Thereafter, thrombolytic therapy with low-molecular-weight heparin was started immediately and switched to a direct oral anticoagulant. The follow-up CT taken 3 months after liver transplantation revealed a patent PV without thrombus; therefore, anticoagulant therapy was discontinued. Currently, the patient has been well and active with a patent PV without anticoagulant therapy for 3 years after LDLT. Conclusions: Retro-pancreatic pull-through reconstruction of the hypoplastic PV is a feasible and effective method when conventional reconstruction is not indicated. [ABSTRACT FROM AUTHOR]

Background and Aims: Critically ill patients with liver failure have high mortality. Besides the management of organ‐specific complications, liver transplantation constitutes a definitive treatment. However, clinicians may hesitate to introduce mechanical ventilation for patients on liver transplantation waitlists because of poor prognosis. This study investigated the outcomes of intensive care and ventilation support therapy effects in patients with liver failure. Methods: This single‐center study retrospectively enrolled 32 consecutive patients with liver failure who were admitted to the intensive care unit from January 2014 to December 2020. The medical records were reviewed and analyzed retrospectively for Acute Physiologic and Chronic Health Evaluation (APACHE)‐II. The model for end‐stage liver disease scores, 90‐day mortality, and survival was assessed using the Kaplan–Meier method. Results: The average patient age was 45.5 ± 20.1 years, and 53% of patients were women. On intensive care unit admission, APACHE‐II and model for end‐stage liver disease scores were 20 and 28, respectively. Among 13 patients considered for liver transplantation, 4 received transplants. Thirteen patients (40.6%) were intubated and mechanically ventilated in the intensive care unit. The 90‐day mortality rate of patients with and without mechanical ventilation in the intensive care unit (13, 61.5% vs. 19, 47.4%, p = 0.4905) was similar. APACHE‐II score >21 was an independent predictor of mechanical ventilation requirement in patients with liver failure during intensive care unit stay. Conclusion: Although critically ill patients with liver failure are at risk of multiorgan failure with poor outcomes, mechanical ventilation did not negatively affect the 90‐day mortality or performance rates of liver transplantation. Clinicians should consider mechanical ventilation‐based life support in critically ill patients with liver failure who are awaiting liver transplantation. Key points: What's known As critically ill patients with liver failure have high mortality, clinicians hesitate to introduce mechanical ventilation for patients on liver‐transplantation waitlists because of the poor prognosis. What's new We aimed to clarify the management and treatment outcomes of patients with liver failure, especially those who needed mechanical ventilation. What the clinical implications of this study are Mechanical ventilation‐based life support is not an adverse prognostic factor for critically ill patients with liver failure who are on a waitlist for liver transplantation. Therefore, clinicians should unhesitatingly provide mechanical ventilation‐based life support in this patient group. [ABSTRACT FROM AUTHOR]

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)‐positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin‐2 (Ang‐2) in VETC‐positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. Results: Forty‐three of the 214 patients (20.1%) were VETC‐positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang‐2 expression was significantly higher in the mTOR‐positive than in the mTOR‐negative group (p = 0.037). Thirty‐four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC‐positive; five of these six patients also had VETC‐positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC‐positive lesions (p = 0.0018). Conclusions: We showed that mTOR expression was higher in the VETC‐positive primary and recurrent lesions than in the VETC‐negative ones. [ABSTRACT FROM AUTHOR]

The article is a response to a letter from Drs. Daungsupawong and Wiwanitkit regarding a previously published article on the COVID-19 vaccine in liver transplant recipients. The authors reported that mRNA vaccines induce similar immune responses in liver transplant recipients as in healthy individuals and recommend that liver transplant recipients receive booster vaccinations. The study was conducted in Japan, where liver transplant recipients have good access to healthcare and have been receiving regular vaccinations and booster vaccinations every 6 months. The authors address concerns about the impact of pre-vaccination infections and the need for frequent measurement of antibody levels. They emphasize the importance of continued research on the prevention and treatment of COVID-19 in liver transplant recipients. [Extracted from the article]

Focuses on the indications and needs for living-related liver transplantation on adults in Japan. Donors in adult-to-adult cases; Estimation of graft volume; Type of donor hepatectomy.