大西 康晴

INTRODUCTION: Hepatic hemangioma is one of the most common benign liver tumors. There are few published reports regarding liver transplantation using liver allografts with hemangioma. PRESENTATION OF CASE: A 45-year-old man was evaluated as a living donor for 19-year-old son with cirrhosis due to hepatic fibrosis. Preoperative investigations revealed 20 and 7mm hemangiomas, at segment 2 (S2) and 4 (S4) respectively. Considering the anatomical relation of S2 hemangioma and Glisson 2, liver graft was designed as left lobe excluded S2 hemangioma by partial resection. Estimated graft recipient weight ratio (GRWR) even after partial resection of hemangioma was reasonable. During the donor operation, a partial hepatic resection of S2 hemangioma was performed. Intraoperative pathologic findings revealed a cavernous hemangioma, and then, the left hepatic graft with the caudate lobe was harvested. Actual GRWR was 0.90%. Donor's postoperative course was uneventful. Recipient's post-operative course was almost uneventful. Postoperative computed tomography of the recipient showed the graft regeneration without increase or recurrence of hemangioma. DISCUSSION: Organ shortage is a major concern in the field of liver transplantation. A novel donor source with a further option is extremely crucial for a guarantee of liver transplantation. We experienced the first case of adult-to-adult living donor liver transplantation using liver allograft after the resection of hemangioma. CONCLUSION: We advocate that the use of liver allograft with hemangiomas in adult-to-adult LDLT settings can be remarkable strategy to reduce the problem of organ shortage without any unfavorable consequences in both living donor and recipient.

The combination of nucleos(t)ide analogues (NAs) and hepatitis B immune globulin has been established as safe and effective prophylaxis against hepatitis B virus (HBV) reactivation after liver transplantation (LT). However, the essential weak point of this regimen is its high cost. The hepatitis B (HB) vaccine is an attractive alternative that costs less, and it enables some patients to have sufficiently high hepatitis B surface antibody (HBsAb) titers. Almost no data exist on whether NAs can be stopped safely in such successfully vaccinated patients. We investigated the incidence of HB vaccine escape mutants in liver recipients who had sufficient HBsAb titers after LT and stopped NAs. Among 18 HBV carriers and 7 non-HBV patients who received grafts from hepatitis B core antibody-positive donors, 2 HBV carriers and 6 non-HBV patients who achieved HBsAb titers >100 IU/L for >3 months after posttransplant vaccination were weaned from NAs. For the patients who showed viremia, we analyzed amino acid sequences of the HB envelope protein, and we performed a statistical analysis for the factors associated with viremia. In 4 of the 8 patients who achieved sufficient HBsAb levels after vaccination and stopped NAs, HBV DNA appeared after a median of 12 months. A sequence analysis showed various amino acid mutations, including the a-determinant, in the HB envelope region. Frequent vaccination was shown to be a statistically significant risk factor for inducing viremia. In conclusion, although the HB vaccine is an effective substitute for prophylaxis against HBV reactivation in some patients after LT, frequent vaccination could be a risk factor for producing escape mutants. Our data demonstrate not only that caution must be exercised in stopping NAs in effectively vaccinated patients (especially in patients vaccinated frequently) but also that it is important to set stopping rules for vaccination in transplant patients.

The availability of a regional team may facilitate the organization and coordination of organ procurement. As a result, regional organ procurement has been reported to reduce costs, streamline logistics, and increase safety for the teams. We herein report a case of brain-dead donor liver transplantation with regional organ procurement. Because of the collaboration between the transplant team and the donor surgery team, the latter being was comprised of a liver transplant team in the local area of the donor hospital, a smooth brain-dead donor liver transplantation was successfully performed. Regional organ procurement is considered achievable in the future with the standardization of organ procurement by the establishment of an educational system for donor surgery.

AIM: Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. METHODS: Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P < 0.05 was considered statistically significant. RESULTS: In multivariate analysis, recipient age (hazard ratio = 1.188, P = 0.011) and FBG (hazard ratio = 1.009, P = 0.016) showed as significant independent factors. Theoretical mortalities were 9.2%, 21.9% and 51.7% in patients with normal FBG at 55, 60 and 65 years old, respectively, and 34.3% and 53.6% in patients with FBG of 150 and 200 mg/dL, respectively, at 60 years old. CONCLUSION: Recipient age and FBG remain important risk factors for LDLT in cirrhotic patients even in the recent era. These factors should be considered for selecting liver transplant candidates in cirrhotic patients.

OBJECTIVE: To elucidate the effect of liver transplantation (LT) on brain dysfunctions in cirrhotic patients who had no clinical evidence of hepatic encephalopathy (HE), we performed a prospective study of voxel-based diffusion tensor imaging (DTI) and detailed cognitive examination. METHODS: We assessed 12 consecutive patients as transplant candidates by DTI, with neurological and cognitive examinations just before and at 6 months after LT. RESULTS: After LT, cirrhotic patients showed significant improvement in visual reproduction, digit symbol, digit span, Stroop test, and Trail-making test scores, suggesting recovery of frontal-temporal function. As for voxel-based DTI, increased mean diffusivity (MD) and reduced fractional anisotropy (FA) values were found before LT in the frontal and temporal lobes of cirrhotic patients. After LT, the unusual FA and MD values observed in the frontal and temporal lobes preoperatively were significantly reduced. CONCLUSION: End-stage cirrhotic patients without clinical evidence of HE showed increased MD and decreased FA values in both frontal and temporal lobes. These parameters improved after LT, in line with cognitive function. MD and FA values might be of value as a biomarker in end-stage cirrhotic patients for investigating brain tissue dysfunctions and evaluating the efficacy of LT.

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

OBJECTIVES: Consensus regarding psychosocial aspects relevant for the liver transplantation indication criteria in case of alcohol-related liver failure remains to be established. Thus we investigated the psychosocial aspects of candidates for liver transplantation for alcohol-related liver failure in order to determine the indication criteria. SUBJECTS: We evaluated the psychosocial aspects of 19 candidates (14 male and 5 female patients) who met the physical liver transplantation indication criteria for alcohol-related liver failure at Nagoya University Hospital between 2004 and 2012. RESULTS: Of the 19 subjects, 4 underwent liver transplantation (average follow-up phase: 42.3 +/- 36.5 months), and 3 were monitored without resuming alcohol consumption. One patient temporarily resumed alcohol consumption at 12 months after transplantation. CONCLUSION: This retrospective study suggested the importance of pre-and post-transplant psychosocial evaluation. A prospective well-designed analysis is essential to determine psychosocial aspects regarding the liver transplantation indication criteria for alcohol-related liver failure.

AIM:   We investigated a protocol that lowered the necessary dose of anti-hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) levels in the early post-transplant period. METHODS:   Fifteen hepatitis B virus (HBV)-positive patients were studied. We administered a nucleoside analog from the preoperative period, high dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and was continued every day (5000-10 000 IU/day). Thereafter, HBIg was administered to keep the target trough titers. We evaluated the effectiveness and safety of this protocol for preventing HBV reactivation. RESULTS:   The average use of HBIg during the first three postoperative months (POM) was 27.9 ± 9.6 Kilo International Units. The average cost was $US11 800 in the first three postoperative months, compared with other previously reported protocols (about $20 000-40 000). HBV reactivation was detected in only one patient (6.7%) during the median follow up of 64 months (range: 12-86 months). CONCLUSIONS:   The present protocol for HBIg administration, which used frequent monitoring of HBsAg and HBsAb levels to determine the minimum required dose, was both safe and effective, and contributed to overall cost saving after liver transplantation.

Living donor liver transplantation (LDLT) has become one of the chief methods of saving patients with end-stage liver disease due to liver cirrhosis. Accumulation of knowledge about indication and perioperative managements improve outcome of this treatment. In this study, we elucidate the risk factors of LDLT, which still exist today. Sixty-one patients received LDLT in our institute between 2003 and 2009 were included in this study. Recipient age and sex, donor age and sex, etiology, preoperative model of end-stage liver disease (MELD) score, hepatocellular carcinoma (HCC), graft versus recipient weight ratio (GRWR), cold and warm ischemic time, operation time, blood loss, ABO compatibility, rejection, cytomegalovirus (CMV) infection, biliary stricture, and calcineurin inhibitor (FK506 or cyclosporin A) were the factors investigated. p < 0.05 was considered as statistically significant in the proportional hazard model. In univariate analysis, the recipients' age (p = 0.024) and rejection episode (p = 0.046) were selected as significant risk factors. In multivariate analysis including the factors that showed p < 0.2 (recipient age, GRWR, ABO compatibility, rejection episode) in univariate analysis, recipient age (p = 0.008, HR: 1.40; 95% CI: 1.09-1.80) and rejection episodes (p = 0.002, HR: 13.33; 95% CI: 2.53-71.43) were still selected as significant independent risk factors after LDLT. Recipient age was shown to be 1.40 times risk per 1 year older and the rejection episode was shown to be 13.33 times risk in the recent era with comprehensive indication and preoperative management for LDLT. Indication must be cautious for elderly patients, and prevention of rejection is crucial for the improvement of results for LDLT.

We encountered a patient with previously well-controlled Wilson disease who experienced fulminant hepatic failure with hemolytic anemia, possibly caused by the dietary supplement Health Proportion(®) (Jubilant Co., Ltd., Ehime, Japan). A 21-year-old woman was admitted to our hospital with marked liver dysfunction and severe hemolytic anemia. Free serum copper level was elevated at 101 μg/dl, and urinary copper excretion was extremely increased (25,600 μg/day). Plasma exchange and continuous hemodiafiltration were performed to remove serum copper and to treat the hemolytic anemia. However, liver function did not improve, and she underwent liver transplantation on 28th day after admission. Copper and iron contents in the resected liver were high at 851.9 μg and 551.7 μg/dry liver weight (g), respectively, despite the patient having regularly taken D-penicillamine since diagnosis and having a well-controlled copper level 1 year before her admission. Two months before admission, the patient had taken a dietary supplement made from soybeans for 1 month. This supplement was labeled as containing large amounts of copper and iron, and we assume that this caused fulminant hepatic failure with hemolytic crisis in this patient. It is important to be mindful of the micronutrient content of dietary supplements, especially for metabolic disorder patients.

A 27-day-old boy had convulsion associated with brain abscesses and severe hypoxemia at the age of 3 months. Congenital absence of the portal vein (CAPV) and some associated anomalies were detected by radiological examinations. Brain abscess and hypoxemia were thought to be serious complications resulting from CAPV and were successfully corrected by living donor liver transplantation at the age of 4 months. This is the first report of a successful transplantation indicated for intrapulmonary shunt and brain abscess in an infant with CAPV.

Autocrine motility factor receptor (AMFR) is a cell surface glycoprotein of 78000 molecular weight (gp78), regulating cell motility signaling in vitro and metastasis in vivo. To test whether AMFR could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 fibroblast cells with expression vectors carrying the full-length cDNA for mouse AMFR and evaluated the effects of increased AMFR on transforming potential. The cells stably expressing high levels of AMFR as a result of transfection displayed a complete morphological change and acquired the ability to grow even in low serum. Furthermore, they were anchorage-independent for growth in soft agar and more motile in phagokinetic track assay. Interestingly, the enhanced expression of AMFR produced tumors in nude mice. Our findings provide a direct evidence that overexpression of the AMFR is associated with the acquisition of a transformation phenotype.