Comparing the risk of hepatitis B virus reactivation between direct-acting antiviral therapies and interferon-based therapies for hepatitis C.

Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti-HCV therapy and compared those between interferon (IFN)-free direct-acting antiviral (DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti-HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV-DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti-HBs positivity, changes in anti-HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti-HBs titre to <12 mIU mL-1 by the end of treatment. The decline changes of anti-HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti-HBs and their decrease to <12 mIU mL-1 after treatment are significant risk factors for HBV reactivation or reappearance.

Splenectomy for Severe Intestinal Bleeding Caused by Portal Hypertensive Enteropathy After Pediatric Living-Donor Liver Transplantation: A Report of Three Cases.

BACKGROUND: The incidence of portal vein thrombosis after pediatric living-donor liver transplantation (LDLT) is reported to be higher than that after deceased-donor or adult liver transplantation. Portal vein thrombosis can cause portal hypertension and related complications, including portal hypertensive gastropathy or portal hypertensive enteropathy (PHE). PHE, in particular, can lead to severe intestinal bleeding, which is extremely difficult to treat. However, the pathogenesis of and appropriate treatment for PHE are not clearly defined, especially after pediatric LDLT. METHODS: Herein, we report three cases of refractory intestinal bleeding caused by PHE after pediatric LDLT, which were treated with splenectomy. RESULTS: The time between LDLT and splenectomy was 43, 92, and 161 months, respectively. All 3 patients were discharged from the hospital without any peri-operative complications and were doing well, with no adverse effects at 174, 81, and 12 months after splenectomy, respectively. Although shunt surgeries, including the use of a meso-Rex shunt, are reported to be a useful option when the portal vein is completely occluded, adhesiotomy around the liver graft would be required, which could damage the hepatopetal collateral vessels that maintain portal vein flow to the graft. Therefore, shunt surgeries, which can lead to re-transplantation, are considered to be highly risky as a first-line treatment option, particularly considering the limited accessibility to deceased donor organs in our country. CONCLUSIONS: Our data demonstrate that simple splenectomy, although considered a palliative treatment, can be a safe and effective method to control severe intestinal bleeding caused by PHE after pediatric LDLT.

Poor Long-Term Outcomes of Adult Liver Transplantation Involving Elderly Living Donors.

BACKGROUND: Donor hepatectomy requires particular care to ensure the safety of the donor and the success of the liver transplantation. The aim of this study was to evaluate the effect of donor age on the postoperative outcomes of liver transplant donors and the long-term graft survival rates. METHODS: We retrospectively reviewed 56 consecutive adult patients who underwent living donor liver transplantation at our institution between April 2001 and August 2010. Donors and recipients were divided into 2 groups, based on the age of the donor: the elderly donor group (donor age ≥50 years) and the younger donor group (donor age <50 years). Perioperative variables, postoperative complication rates, and long-term graft survival rates were compared between the 2 groups. RESULTS: The average ages in the elderly donor group and younger donor group were 58 years and 32 years, respectively. Baseline data excluding the age of the donor did not differ between the groups, nor did the overall complication rates of the donors. Hospital stays were longer in the elderly donor group than in the younger donor group (25 vs 18 days, P < .05). The 1-, 3-, and 5-year graft survival rates were 80%, 60%, and 50% in the elderly donor group, and 89%, 87%, and 82% in the younger donor group, respectively (P = .0002). CONCLUSIONS: Donor hepatectomy can be performed safely in elderly patients. However, compared with younger donors, their hospital stays were longer and the graft survival rates were shorter.

The Significance of Screening for HLA Antibodies in the Long-Term Follow-up of Pediatric Liver Transplant Recipients.

BACKGROUND: Post-transplant donor-specific anti-HLA antibodies (DSA) reportedly have detrimental effects on the outcomes of organ transplantation. However, the prevalence of post-transplant DSA in the long term after pediatric liver transplantation remains unclear, and the significance of post-transplant DSA is unknown. The aim of this cross-sectional study was to determine the prevalence of and characteristics of patients with post-transplant DSA. MATERIALS AND METHODS: Of the 84 pediatric liver transplant recipients who were followed up in the outpatient department of our institution, 34 patients with available HLA typing data were included after they or their parent(s) provided informed consent for DSA evaluations. Luminex single-antigen bead assays were performed, and a mean fluorescence intensity of ≥1000 was used as the cut-off for a positive reaction. RESULTS: No class I DSA were detected, whereas class II DSA were detected in 11 patients (32%). There were no differences in age at transplantation, immunosuppressive drugs, or follow-up period between the DSA-positive and DSA-negative patients. The rate of positive pre-transplant complement-dependent cytotoxicity crossmatch was higher with class II DSA than without, although the difference was not statistically significant. CONCLUSIONS: The utility of screening for class I DSA was insignificant in the long-term follow-up of pediatric liver transplant recipients. The prevalence of class II DSA was relatively high; therefore, screening for class II DSA might be justified, although a follow-up survey of the association between post-transplant class II DSA and the long-term clinical course needs to be conducted.

Relationship Between Bile Duct Reconstruction and Complications in Living Donor Liver Transplantation.

OBJECTIVES: In living donor liver transplantation (LDLT), the recipient bile duct is thin and short. Bile duct complications often occur in LDLT, with persistent long-term adverse effects. Recently, we began to perform microsurgical reconstruction of the bile duct. The purpose of this study was to investigate the relationship between bile duct reconstruction methods and complications in LDLT. METHODS: From 1991 to 2014, we performed 161 LDLTs (pediatric:adult = 90:71; left lobe:right lobe = 95:66). In this study, we retrospectively investigated the initial bile duct complications in LDLT and performed univariate and multivariate analyses to identify the independent risk factors for complications. RESULTS: The most frequent complication was biliary stricture (9.9%), followed by biliary leakage (6.8%). On univariate and multiple logistic regression analysis, the independent risk factors for biliary stricture were bile leakage (P = .0103) and recurrent cholangitis (P = .0077). However, there were no risk factors for biliary leakage on univariate analysis in our study. The reconstruction methods (hepaticojejunostomy or duct-to-duct anastomosis) and reconstruction technique (with or without microsurgery) were not risk factors for biliary stricture and leakage. CONCLUSION: In this study, the most frequent complication of LDLT was biliary stricture. The independent risk factors for biliary stricture were biliary leakage and recurrent cholangitis. Duct-to-duct anastomosis and microsurgical reconstruction of the bile duct were not risk factors for biliary stricture and leakage.

Resveratrol Prevents Warm Ischemia-Reperfusion Injury in Liver Grafts From Non-Heart-Beating Donor Rats.

BACKGROUND: Successful liver transplantation from non-heart-beating donors (NHBDs) might enlarge donor source. Some studies have reported that resveratrol (RES), an activator of sirtuins, has cytoprotective effects on ischemia-reperfusion (I/R) injury. The purpose of this study was to investigate the effects of RES on warm I/R injury in rats. METHODS: Male Wister rats were divided into 5 groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the NHB group, whose livers were retrieved under apnea-induced NHB conditions; (3) the ethanol group, retrieved in the same manner as the NHB group with ethanol (10 µL) as a solvent; (4) the RES-1 group, retrieved in the same manner as the NHB group and pretreated with RES (0.4 mg/kg, dissolved in 10 µL ethanol); and (5) the RES-2 group, retrieved in the same manner as the NHB group and pretreated with RES (2 mg/kg, dissolved in 10 µL ethanol). The resected livers were perfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after 6 hours of cold preservation, after which the perfusate and liver tissues were investigated. RESULTS: The bile production, portal vein flow volume, tumor necrosis factor-α level, and adenosine triphosphate level in the RES-2 group were significantly improved compared with in the NHB group. Histology revealed numerous well-preserved sinusoidal endothelial cells in the RES-2 group. CONCLUSIONS: RES might reduce warm I/R injury and improve the viability of liver grafts from NHBDs. We considered that this method may represent a promising approach for clinical liver transplantation from NHBDs.

Successful Case of Somatostatin Analog Stopping Gastrointestinal Bleeding, One of the Most Frequent Complications After Simultaneous Pancreas-kidney Transplantation: A Case Report.

OBJECT: Pancreas transplantation has the highest surgical complication rate of all routinely performed organ transplantation procedures. The complications are not only caused by the pancreas itself but also occur due to issues with the transplant recipient. We report the case of a patient who experienced massive gastrointestinal bleeding after simultaneous pancreas-kidney transplantation (SPK), which was stopped successfully using somatostatin analog. PATIENTS AND METHODS: The patient was a 45-year-old woman with diabetes mellitus type 1 who underwent SPK with enteric drainage. She had melena 5 days after SPK. RESULTS: At first, we suspected that the melena was caused by the transplanted duodenum because of rejection and ischemic changes. The patient experienced severe bleeding 9 days after SPK. We quickly performed open surgery and inserted an endoscope from the recipient's ileum to investigate the transplanted duodenum. However, no bleeding source was found, including in the transplanted duodenum and the recipient's ileum end. We determined that the bleeding source was the recipient's ascending colon. We attempted to perform endovascular treatment but could not detect the source of the bleeding; therefore, we used somatostatin analog to let the blood vessels shrink and reduce pancreatic output. Thereafter, the function of the transplanted pancreas and kidney gradually recovered, and the recipient was discharged 154 days after SPK. CONCLUSION: Gastrointestinal bleeding is a lethal complication and has several different causes, such as mucosal rejection, ischemic changes, and exocrine output of the pancreas graft. Somatostatin analog is one of the most acceptable treatments for patients who have gastrointestinal bleeding after SPK.

Long-term complete remission of multiple extranodal natural killer/T-cell-type posttransplant lymphoproliferative disorder after surgical resection: a case report.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation that results from immunosuppression therapy. Most cases of PTLD derive from the B-cell lineage. T-cell PTLD, particularly natural killer (NK)/T-cell PTLD, is quite rare; only a few cases have been described. CASE REPORT: A 42-year-old woman received a living-related renal allograft from her father. Sixteen years after transplantation, the patient presented with a 1-week history of low-grade fever and epigastralgia. Computed tomography revealed intestinal masses and a right upper lung lobe mass. Gallium scintigraphy showed uptake in the abdominal mass. Epstein-Barr virus-related antibody was not detected in the patient's serum sample. We performed extirpation of the jejunum and ileum tumors. The pathologic findings showed that these 2 tumors were NK/T-cell lymphoma. After the operation, the lung mass rapidly enlarged, and right upper lobectomy was performed. The right upper lung lobe tumor showed the same histopathologic findings as the small bowel tumor. The final histologic diagnosis was established as multiple extranodal NK/T cell type PTLD of the small bowel and right upper lung lobe. CONCLUSIONS: After reduction of the immunosuppressive agent, no recurrence of PTLD has been observed for the past 9 years.

Edaravone, a free radical scavenger, improves the graft viability on liver transplantation from non-heart-beating donors in pigs.

BACKGROUND: Although liver transplantation from non-heart-beating donors (NHBDs) is an effective way to overcome shortage of donors, primary graft nonfunction is often noted in these grafts. We have previously reported that edaravone, a free radical scavenger, has a cytoprotective effect on warm ischemia-reperfusion injury and improves the function of liver grafts from NHBDs in a rat model of ischemia-reperfusion. The purpose of this study was to investigate the effects of edaravone on liver transplantations from NHBDs. METHODS: Pigs were divided into three groups: (1) a heart-beating (HB) group (n = 5), in which liver grafts were retrieved from HB donors; (2) a non-heart-beating (NHB) group (n = 4), in which liver grafts were retrieved under apnea-induced NHB conditions; and (3) an edaravone-treated (ED) group (n = 5), in which liver grafts were retrieved in the same manner as the NHB group and treated with edaravone at the time of perfusion (3 mg/L in University of Wisconsin [UW] solution), cold preservation (1 mg/L in UW solution), and after surgery (1 mg/kg/d). The grafts from all groups were transplanted after 4 hours of cold preservation. RESULTS: In the ED group, the 7-day survival rate was significantly higher than that in the NHB group (80% versus 0%, P = .0042, Kaplan-Meier log-rank test). Furthermore, on histologic examination, the structure of sinusoids in the ED group was well preserved and similar to that in the HB group. CONCLUSIONS: Edaravone may improve the viability of liver grafts from NHBDs.

Donors' quality of life evaluated by short form-36 analysis after living donor liver transplantation in a single-center experience.

BACKGROUND AND PURPOSE: The purpose of this study was to compare the quality of life of donors using the Short Form 36 (SF-36) analysis between the left and right graft periods of living donor liver transplantation. PATIENTS AND METHODS: In the left graft period (July 1991 to July 2003), 68 donors were eligible for analysis and 76 were eligible in the right graft period (August 2003 to October 2010). Nine right lobe grafts were included in the left graft period, and 52 right lobe grafts were included in the right graft period. We investigated the risks of donation and evaluated the following: blood loss, operation time, postoperative liver function, and duration of hospitalization. We also assessed quality of life in donors, who were mailed a structured questionnaire and the SF-36. RESULTS: Ten of the 68 donors in the left graft period and 12 of the 76 in the right graft period had postoperative complications. Most postoperative complications were treated without surgical procedures. There was no donor death in our series. Forty-eight donors in the left graft period and 36 in the right graft period responded to our investigation. Compared with published Japanese norms in SF-36, our donors scored similar or higher than the general population in both groups. Two donors in the left graft period and one in the right graft period regretted their decisions to donate. All donors returned to normalcy. CONCLUSIONS: These results suggested that the donors' quality of life was guaranteed in terms of the SF-36 investigation regardless of the donation period in our series.

Risk factors for portal vein stenosis in living-donor liver transplantation.

BACKGROUND: In living-donor liver transplantation (LDLT), the recipient's portal vein is short. Furthermore, portal vein thrombosis and stenosis can be lethal complications. We had begun the systemic administration of gabexate mesilate, a strong serine protease inhibitor, which has cytoprotective effects of endothelial cells. It is often effective on disseminated intravascular coagulation. The purpose of this study was to examine the effects of gabexate mesilate and to reveal risk factors for portal vein stenosis in LDLT. METHODS: From 1991 to 2012, we performed 153 LDLTs. For the present cohort study, patients were divided into 2 groups. In group I, we treated with gabexate mesilate mildly (0-20 mg/kg/d; n = 29). In group II, we treated with gabexate mesilate at full dose (40 mg/kg/d; n = 124). We investigated the survival rates of both groups and performed univariate and multivariate analyses to identify the independent risk factors for portal vein stenosis. RESULTS: The survival rate of group II was significantly better than that of group I (P < .05). On univariate analysis, the risk factors identified to be associated with a P value of <.20 were old age (P = .0385), heavy body weight (P = .1840), tall height (P = .1122), small lumen diameter of portal vein (P = .1379), high volume of blood loss (P = .0589), small amount of gabexate mesilate infusion (P = .0103), and large graft weight (P = .1326). On multiple logistic regression analysis we identified old age (P = .0073) and small amount of gabexate mesilate infusion (P = .0339) to be the independent risk factors for portal vein stenosis. CONCLUSIONS: On multivariate analysis, we found that gabexate mesilate infusion contributed to the reduction of portal vein stenosis.

Impact of the 2011 Great East Japan Earthquake on the resumption of alcohol consumption after living-donor liver transplantation for alcoholic cirrhosis: a report of two cases.

Alcoholic liver disease (ALD) is a leading indication for liver transplantation (LT) in Western countries. The rate of resumption of alcohol abuse is 7% to 95% after LT for ALD. A high prevalence of alcohol abuse has been observed in disaster-exposed populations; however, little is known about the association between resumption of alcohol abuse after LT and disasters. Between June 2007 and March 2011, 3 patients with alcoholic cirrhosis (2 men and 1 woman) underwent living-donor LT (LDLT) at Tohoku University Hospital, Sendai, Japan. The female patient died of graft failure 6 months after LDLT. The other patients (ages 55 and 56 years), who survived to discharge, resumed alcohol abuse after the 2011 Great East Japan Earthquake. Before transplantation, both patients had been abusing alcohol for >35 years, with a daily ethanol intake of 110 g and 140 g, respectively. The period of abstinence from alcohol consumption ranged from 4 to 6 months. After transplantation, patients showed good compliance with treatment and seemed at low risk of relapse until the earthquake. One patient was living in the nuclear evacuation zone at Fukushima, and resumed alcohol consumption after the evacuation. Another patient resumed alcohol consumption while temporarily living apart from his family during restoration work after the disaster. Extreme stress and changes in living arrangements after the Great East Japan Earthquake seemed to trigger the desire to drink. This is the first report on patients who underwent LT for ALD and who resumed alcohol consumption after a disaster.

Fibrosing cholestatic hepatitis developing within one month after living donor liver transplantation for chronic hepatitis C-related cirrhosis: a case report.

Fibrosing cholestatic hepatitis (FCH) is a life-threatening consequence of hepatitis C virus (HCV) infection occurring in a small minority of liver transplantation (LT) recipients. We herein report a case of early-onset FCH after living donor LT in a 47-year-old woman with HCV-related cirrhosis. The patient underwent balloon-occluded retrograde transvenous obliteration of a splenorenal shunt to treat an impaired portal flow on the sixth postoperative day (POD 6) and a bypass operation for hepatic artery thrombosis on POD 12. Thereafter, the serum bilirubin levels increased gradually; however, computed tomography revealed no evidence of biliary stricture. The serum HCV-RNA level on POD 27 was >7.8 log IU/mL. Histopathology of a needle graft biopsy performed on POD 28 revealed FCH with extensive portal fibrosis accompanied by mild inflammation, hepatocyte ballooning, and ductular proliferation with cholestasis. The patient received combination therapy with pegylated interferon, ribavirin, and double-filtration plasmapheresis for the treatment of early-onset FCH. Both the recipient and the donor carried the major genotype single nucleotide polymorphism (TT) at rs8099917 near the interleukin-28B gene. Furthermore, the HCV genotype was treatment-sensitive 2a. Nonetheless, the recipient died of hepatic failure on POD 211. Thus far, few cases of FCH occurring within 1 month after LT have been reported. In addition, the early onset of FCH may be an adverse prognostic factor.

Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.

We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type-incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit-bound status, high Model for End-Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody-mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add-on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the latest era coincident with the introduction of rituximab.

The optimal timing for preparation of recipient superficial femoral veins to minimize intraoperative blood loss in living donor liver transplantation.

AIMS: Intraoperative blood loss (IBL) usually predominates during the dissection of the native liver. A right-lobe living donor liver transplantation (LDLT) sometimes requires an additional procedure to obtain an autologous vein from the recipient for the vascular reconstruction. These procedure can sometime contribute to progressive coagulopathy causing unexpected bleeding. Therefore, we analyzed our cases to determine the optimal timing for vascular preparation from the patient in terms of IBL. METHODS: Among 67 patients included in the study, 30 did not require an additional procedure to obtain the venous graft (group A), and 37 LDLT employed a superficial femoral vein (SFV). Of these, 13 had undergone removal of SFV after the hilar dissection and liver mobilization from retrohepatic area while preserving the inferior vena cava (group B), and 24 removal of the SFV immediately after hilar dissection without liver mobilization from the retrohepatic space (group C). RESULTS: A significant difference existed only in the scores of the Model for End-stage Liver Disease. Although the median IBL for group C was similar to that for group A, the median IBL for group B was significantly higher than that for other 2 groups. The median duration from skin incision to graft implantation for group B was significantly longer than that for groups A and group C, because of the additional hemostatic procedures in the retrohepatic space including the leg site. CONCLUSIONS: The timing for removal of SFV in LDLT patients affects IBL associated with consumptive coagulopathy and prolongs operative time. Based on our experience, we concluded that SFV preparation should be performed before liver mobilization from the retrohepatic area to minimize IBL.

Risk factors for hepatic artery thrombosis after microsurgical vascular reconstruction in liver transplantation.

OBJECTIVE: In liver transplantation, microsurgical reconstruction of a hepatic artery is essential but requires challenging techniques. Especially in living-donor liver transplantation, the recipient artery is short and located deep in the abdominal cavity. Furthermore, hepatic artery thrombosis (HAT) can be a lethal complication. This study sought to uncover the risk factors for HAT after microsurgical vascular reconstruction. METHODS: From 1991 to 2011, we performed 151 microsurgical vascular reconstructions, including 3 deceased-donor liver transplantations. We retrospectively investigated the cases, performing univariate and multivariate analyses to identify independent risk factors for HAT. The patients had undergone ultrasonographic examinations for HAT over the first 14 days after transplantation. RESULTS: Upon univariate analysis, the risk factors identified to be associated with P < .20 were young age (P = .0484), low body weight (P = .0466), short height (P = .0128), high graft-to-recipient weight ratio (P = .0031), small liver graft volume (P = .0416), small amounts of gabexate mesilate infusion (P = .0516), and the conventional technique (without a back-wall support suture; P = .1326). A multiple logistic regression analysis identified low body weight to be the only independent risk factor for HAT. CONCLUSION: On the univariate analysis, we found that using the back-wall support suture technique contributed to the reduction of HAT, whereas on multivariate analysis, the only independent risk factor for HAT was low body weight.

A patient with hepatic artery thrombosis after living-donor liver transplantation survived the great East Japan earthquake 3 days after reoperation: a case report.

BACKGROUND: On March 11, 2011, our hospital was severely damaged by the Great East Japan Earthquake. We report the rare case of a 5-month-old patient with hepatic artery thrombosis (HAT) after living donor liver transplantation (LDLT), who survived the earthquake that occurred 3 days after the reoperation; we were able to save this patient without abilities to perform blood tests or computed tomography (CT) for 4 days. METHODS: This female infant with biliary atresia underwent LDLT 5 months after birth and developed peritonitis owing to perforation of the small intestine 7 days later. Her blood pressure decreased and she developed HAT. We performed emergency reconstruction of the hepatic artery and repair of the small intestine, and 3 days after surgery, the Great East Japan Earthquake occurred. RESULTS: We could not perform blood tests or CT scans because the water supply was damaged. Gas supply lines were also damaged and sterilization was not possible; surgical tools were limited. However, emergency power was available, so we performed ultrasonography every 6 hours and predicted liver function from intrahepatic blood flow and monitored for Glisson's capsule edema. The blood examination system recovered 14 days after LDLT, and we confirmed improvement of liver function. The patient was extubated 37 days after LDLT and discharged on postoperative day 67. CONCLUSIONS: Portable ultrasonography was useful in evaluating intrahepatic blood flow and Glisson's capsule edema. Furthermore, it was effective during a disaster because it required no water or gas.

The relationship between recurrences and immunosuppression on living donor liver transplantation for hepatocellular carcinoma.

OBJECTIVES: Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the needs for pretransplantation treatments may be eliminated. It is known that negative impacts of immunosuppression are limited among LDLT for HCC, however, we believe that excessive immunosuppression is one of the risk factors for recurrence. We compared the impacts of immunosuppression for LDLT with hepatectomy outcomes for HCC. METHODS: From 1991 to 2010, we performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria. Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC cases from 1997 to 2010. RESULTS: Overall survival rates of the LDLT cohort and hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of the LDLT cohort were significantly better than those of the hepatectomy group (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus 33.8%). Thus, the negative impact of immunosuppression on recurrence was less than the benefit of a whole liver resection. Among strongly immunosuppressed cases, 5-years DFS rates were significantly worse than among other immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the factors associated with HCC recurrence were alpha-fetoprotein levels and steroid doses within 180 days, but multivariate analysis did not show a predictor for recurrence. CONCLUSION: Patients who are strongly immunosuppressed may have several negative impacts for recurrences. More careful indications must be selected for ABO-incompatible cases.

Recombinant human soluble thrombomodulin (ART-123) prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

BACKGROUND: Liver transplantation is an established treatment for end-stage liver disease. However, an ongoing problem worldwide concerning this treatment is the shortage of grafts. Although transplantation using grafts from non-heart-beating donors (NHBDs) is considered a promising solution, some researchers have reported that these liver grafts are associated with primary graft nonfunction and biliary complications. The purpose of this study was to establish a safe technique procuring liver grafts from marginal donors such as NHBDs. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group, whose livers were retrieved from NHBDs that had experienced an apnea-induced agonal condition (for this group, livers were subjected to warm ischemia for 30 minutes after cardiac arrest); and (3) the recombinant human soluble thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. RESULTS: Bile production and portal flow volume in the ART-123 group were significantly higher than those in the NHB group. Alanine aminotransferase levels in the ART-123 group were significantly lower than those in the NHB group. Histological findings showed the narrowing of sinusoidal spaces and necroses in the NHB group were more severe than those in the ART-123 group. CONCLUSIONS: These results suggest that thrombomodulin may improve the viability of liver grafts from NHBDs.

Nonmarginal-donor duodenal ulcers caused by rejection after simultaneous pancreas and kidney transplantation: a case report.

OBJECTIVE: Pancreas transplantation has been associated with the highest surgical complication rate among routinely performed organ transplant procedures. Complications can be caused not only from the pancreas itself but also from the simultaneously transplanted duodenum: gastrointestinal bleeding, duodenal ulcer, pseudoaneurysm, arterioenteric fistula, and severe rejection. Herein we report a patient who underwent simultaneous pancreas-kidney transplantation (SPKT) and experienced a duodenal perforation because of rejection. METHODS: The 60-year-old man with insulin-dependent diabetes underwent SPKT with enteric drainage. At 15 days there after he displayed melena. RESULTS: We suspected it to be caused by rejection and ischemic changes. We slightly increased the doses, of tacrolimus and methylprednisolone. But 17 days after SPKT, the ulcer perforated, requiring a repair operation and increased dose of mycophenolate mofetil. However, the ulcers perforated repeatedly, requiring 4 repair operations. Unfortunately the patient developed pneumonia that mitigated continues repairs or rejection therapies, so we expated the duodenum and pancreas but saved the kidney. The pathologic findings showed the ulcer to have been caused by severe rejection. Despite those episodes, the patient was weaned from hemodialysis. CONCLUSIONS: Perforation of the transplanted duodenum is one of the most difficult complications among SPKT patients. This potentially lethal complication may be caused by mucosal rejection, ischemic changes, and the exocrine output from the pancreatic graft.