Takashi Orii

Usefulness of quantitative real‐time polymerase chain reaction in following up patients with Epstein–Barr virus infection after liver transplantation

Background. Post‐transplant lymphoproliferative disease (PTLD), which is mainly induced by Epstein–Barr virus (EBV) infection, is a cause of significant morbidity and mortality for patients undergoing liver transplantation, especially when it is detected at such an advanced stage as monoclonal malignant lymphoma. 
Methods. In this series, 6 of 22 1iver transplant patients suffered from EBV infection. We tested quantitative DNA (Qt‐DNA) by real‐time polymerase chain reacton (PCR), qualitative DNA in plasma (Ql‐pDNA) by PCR, and EBV‐encoded mRNA 1 (EBER 1) by in situ hybridization to clarify which of them is a better marker for the early diagnosis and prediction of EBV‐associated disorders. 
Results. Four had signs or symptoms of PTLD, but 2 did not develop individualized lymphoid lesions. In all patients, both Qt‐DNA and EBER 1 exceeded the cut‐off level of 102.5 copies/μg DNA and 0.002%, respectively, at the time of diagnosis. In 2 patients, when Qt‐DNA had a poor decline, EBER 1, even if it seemed to decrease after antiviral therapy, increased again after a few months and the clinical symptoms recurred. In 2 patients, Qt‐DNA and EBER 1 increased again after a few months of antiviral therapy, and Ql‐pDNA remained positive, whereas, in 3 patients, no reaction of EBV could be detected once Ql‐pDNA became negative, even after the cessation of therapy. 
Conclusions. These results suggest that real‐time PCR for Qt‐DNA was more sensitive to the real‐time activity of EBV and that Ql‐pDNA could indicate when to stop antiviral therapy.

Elimination of Kupffer cells and nafamostat mesilate rinse prevent reperfusion injury in liver grafts from agonal non-heart-beating donors.

BACKGROUND We hypothesized that microcirculatory disturbance was an obstacle to liver transplantation (LTx) from non-heart-beating donors (NHBDs) and that it was attributed mainly to a deterioration of sinusoidal endothelial cells (SECs) and sinusoidal narrowing. This study was designed to examine porcine orthotopic LTx using livers obtained from pretreated agonal NHBDs, and to determine whether the maintenance of the liver microcirculation would result in successful LTx from agonal NHBDs. METHODS Pigs were allocated to five groups: (i) control group; (ii) NM group, in which grafts were rinsed with nafamostat mesilate (NM) rinse; (iii) LD group, in which Kupffer cells in grafts were eliminated by liposome-encapsulated dichloromethylene diphosphonate (L-DMDP); (iv) LDNM group, in which grafts pretreated with L-DMDP were rinsed with NM rinse; (v) heart-beating donor (HBD) group. In all groups, but the HBD group, the livers were pretreated with FK506 and prostaglandin I2 analogue, and were preserved in University of Wisconsin solution after cardiac arrest. Thereafter orthotopic LTx was performed. RESULTS After reperfusion, it was histologically demonstrated that elimination of Kupffer cells prevented SECs deterioration and NM rinse prevented sinusoidal narrowing. The hepatic energy charge recovered in all groups except the control group. In the LDNM group, three of four recipients survived more than 7 days. CONCLUSIONS For a successful LTx from agonal NHBDs, it is important to prevent microcirculatory disturbance caused by SEC deterioration and sinusoidal narrowing after reperfusion. Combination therapy consisting in the elimination of Kupffer cells and NM rinse prevented primary graft non-function in liver grafts from agonal NHBDs.

Liver transplantation for severe hypoxemia caused by patent ductus venosus

The authors describe the case of a 9-year-old girl who underwent liver transplantation because she suffered from severe hypoxemia caused by patent ductus venosus (PDV). Generally, severe hypoxemia (PaO2 < 50 mm Hg in room air or < 300 mm Hg in pure oxygen) is not an indication for liver transplantation because the hypoxemia may not be improved, and may lead to a fatal outcome. PDV, which is associated with mild liver dysfunction, is not an indication for liver transplantation by itself. But in our patient, most of the mesenteric venous flow directly entered the systemic circulation through the PDV just like the portosystemic shunt, and this caused the pulmonary arteriovenous shunt and hypoxemia. Thus, the authors operated on the patient in an attempt to restore her pulmonary function. Nitric oxide (10 to 20 ppm) was added to the inhaled gas to dilate the functional pulmonary capillaries and to deliver sufficient oxygen after the transplantation. Although the patient suffered various complications after the operation, the final results were excellent.

Reactivation of hepatitis and lamivudine therapy in 11 HBsAg‐positive renal allograft recipients: a single centre experience

Abstract:  Background:  In hepatitis B virus (HBV) surface antigen (HBsAg) (+) renal allograft recipients, the mortality associated with liver disease reaches 37–78%. An antiviral agent, lamivudine, has recently been reported to be safe and effective for preventing hepatic damage in these patients, although either resurgence of HBV‐DNA levels after discontinuation or emerging resistant HBV mutants caused by long‐term administration are still unsettled.

Efficacy of a liver resection for hepatocellular carcinoma in patients with chronic renal failure

PurposeAs there is still little information available on hepatic resection in patients with chronic renal failure (CRF) in the literature, it is believed that a liver resection for HCC in CRF patients with various related complications is always risky.MethodsWe retrospectively reviewed the clinical and pathological records of 17 patients with CRF who had undergone hepatectomy for HCC, and of 51 non-CRF patients subjected to hepatectomy for HCC during the same period.ResultsThe operative and pathological findings were comparable between the two groups. Postoperative circulatory insufficiency occurred more frequently in the CRF group (P = 0.013). Although the disease-free survival rates were comparable between the two groups, the overall survival rates were significantly lower in the CRF group than in the non-CRF group (P = 0.031).ConclusionsA hepatectomy for HCC should be considered even for CRF patients with various complications if careful perioperative management and suitable multidisciplinary treatment for recurrent disease are provided.

Arterial reconstruction using vein graft from the common iliac artery after hepatic artery thrombosis in living-related liver transplantation.

VASCULAR complications in liver transplantation sometimes occur and may be lethal both for the transplant graft and the patient. Thrombosis at the anastomosis of the hepatic artery is the most common complication in children. Several methods of hepatic arterial reconstruction have been reported, including use of recipient splenic artery, interposition of vessel graft between common hepatic artery and graft artery, and use of conduit between aorta and the graft. We report herein the case of a patient with hepatic arterial reconstruction using vein graft between the common iliac artery and the graft artery after hepatic artery thrombosis in living-related liver transplantation.

Assessment of liver graft function after cold preservation using 31P and 23Na magnetic resonance spectroscopy

We investigated the functional damages of the cytoplasm and the cell membrane of liver grafts in male Wister Kyoto rats after 24-hr and 48-hr cold preservations using the University of Wisconsin solution in vitro. Fructose (10 mM) or NH4Cl (50 mM) was added to the perfusate, and synthesis of fructose-1-phosphate (F-1-P) and Na- and H-ion transports through the cell membrane were evaluated by magnetic resonance spectroscopy (MRS), 31P-MRS and 23Na-MRS. After 30 min of reperfusion, beta-ATP/(inorganic phosphate: Pi) of the 48-hr preserved group was significantly lower than the control group and the 24-hr preserved group. The changes of F-1-P in the control group and the 24-hr preserved group were almost the same, but F-1-P synthesis was lower in the 48-hr preserved liver than those of the other groups. Intracellular pH began to drop after the cessation of NH4Cl loading, and then it recovered to the preloading level. At the same time Nain+ was increased in the control group. However, in the other two groups, the increasing rates of Nain+ were lower, and the recoveries of Nain+ were less. In conclusion, the function of cell membrane was more fragile than that of mitochondria and cytoplasmic sugar metabolism in the liver graft.

Elimination of kupffer cells and administration of protease inhibitor improve graft viability and prevent reperfusion injury In NHBD

T HE SHORTAGE of donors has become a serious problem in liver transplantation (LTX). IF the liver graft from a non-heartbeating donor (NHBD) was available for LTX, the supply could be improved. But a liver graft from NHBD has not been suitable for LTX because the graft viability is deteriorated by warm ischemic injury and severe reperfusion injury. Over the past few years a considerable number of studies has been done on the mechanisms of warm ischemic injury and reperfusion injury. Many agents effective for these injuries, have also been reported. The aim of this study is to determine whether liver grafts from NHBD are suitable for clinical LTX.

Rehospitalization after pediatric living-donor liver transplantation.

Background. Although rehospitalization is one of the factors affecting quality of life after successful liver transplantation, the effects of rehospitalization have not been assessed to date. Patients and Methods. Of 40 consecutive cases of pediatric living-donor liver transplantation (LDLT) performed between April 1994 and October 2000, 28 patients with a graft survival of more than 1 year were enrolled in this study to examine rehospitalization after successful LDLT. The rate and cause of rehospitalization were analyzed retrospectively on the basis of medical records. Results. A total of 23 of the 28 patients were rehospitalized. There were 84 episodes of rehospitalization. The mean number of rehospitalization days per episode per patient was 21.06±21.02 days. The rate of total rehospitalization days to the days after the hospitalization for LDLT was 6.56%±8.73%. Rehospitalization episodes were attributable to the following: cholangitis (21.4%), viral infection (16.7%), and portal stenosis (PS) (13.1%). Rehospitalization as the result of rejection accounted for 9.5% of the episodes. The period of rehospitalization was long in the case of cholangitis (49.7±62.4 days), PS (13.8±13.4 days), and rejection (52.9±45.4 days). Although there were a lot of rehospitalization episodes as the result of viral infection subsequent to cholangitis, each rehospitalization period lasted 4.4±6.6 days. Conclusion. It is suggested that prevention of cholangitis and PS, which were the causes of frequent and long rehospitalization periods, would result in a reduction of rehospitalization and therefore a better quality of life after pediatric LDLT.

New strategy for liver transplantation from non-heart-beating donors.

THE shortage of donors has become a serious problem in liver transplantation (LTx). LTx from controlled non-heart-beating donors (NHBD) has been attempted. However, it has been reported that the grafts from NHBD develop primary graft nonfunction more often than those from heart-beating donors. The aim of this study was to discover a safer method to prevent ischemia and reperfusion injuries in liver grafts from NHBD.