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Background/aims: In living donor liver transplantation (LDLT), donor safety has top priority, and donor morbidity should be minimized to zero. However, several corporal problems still remain. The effect of hyperbaric oxygenation treatment (HBO) was evaluated for donor morbidity in LDLT., Methodology: A total of 14 consecutive donors were studied. The donors into were divided into 2 groups as follows: HBO group (n=7), which started HBO 3 days after operation, and a control group (n=7). Patient's factors, graft volume, liver regeneration rate, liver function tests and postoperative complications ware compared between the 2 groups., Results: There was no significant difference between the groups in whole liver, graft and remnant liver volume. The incidence of wound numbness on POD 28 was 86% (6/7) in the control group and 29% (2/7) in the HBO group (p<0.05). Postoperative hospital stay was 14.4 and 14.6 days in the control and HBO group, respectively (p=NS). On POD 14, AST value in the HBO group was significantly lower than in the control group (p<0.05). PT% value in the HBO group was significantly higher than in the control group on POD 14 (p<0.05). Total bilirubin level in the HBO group was significantly lower than in the control group on POD 14 and 28 (p<0.05), and total bile acid value in the HBO group was significantly lower than the control group (p<0.05) on POD 14. Albumin level in the HBO group was significantly higher than the control group on POD 7, 10 and 28 (p<0.05). Four weeks after the operation, the regeneration rate was significantly higher in the HBO group than in the control group (p<0.05)., Conclusions: Liver regeneration was promoted by HBO preserving a function in LDLT using left lobe graft. Hyperbaric oxygen therapy seems to be very useful to LDLT.

Background/aims: In cadaveric liver transplantation, it has been reported that elderly recipients over 60 years are at risk because of high incidence of complication and malignancy. However, in living-donor adult liver transplantation (LDALT), it is unclear whether the elderly recipient is risky or not risky. In this study, the outcome after LDALT of elderly patients has been evaluated., Methodology: One hundred twenty two consecutive LDALT recipients were studied. The recipients were divided into an elderly group (older than 60 yrs, n = 21), and a control group (younger than 60 yrs, n = 101). Comparative examination of background factors, postoperative complications and de novo malignancy was carried out., Results: Elderly patients more frequently received transplantation for hepatocellular carcinoma. Pretransplant liver damage such as Child-Pugh, MELD or bilirubin level was same among the groups. There was no significant difference in posttransplant complications except renal failure. Postoperative renal failure (postoperative creatinine level over 2mg/dL) occurred in 29% (n = 5) of the elderly group vs. 8% (n = 6) of the control group. De novo malignancy occurred in 1 case (lung) in the elderly group and 1 case (Vater) in the control group. In the control group, the 1, 3 and 5 year patient survival rates were 78.5%, 73.1% and 71.4%, respectively. And in the elderly group, the 1, 3 and 5 year patient survival rates were 85.7%, 81.0% and 70.8%, respectively., Conclusions: It may be, we concluded that living donor adult liver transplantation is good treatment for end stage liver diseases in elderly recipients over 60 years. However caution should be taken in the administration of medicine, including immunosuppressants or antibiotics, do to a propensity for postoperative renal failure in elderly recipients.

Background/aims: Xenogeneic-hepatocyte or liver-fragment transplantation could be an attractive clinical option in hepatic surgery for patients with impaired liver function if xenogeneic hepatocytes or liver fragments could be preserved for lengthy periods and if immunoisolation could be more easily achieved., Methodology: Porcine fetal and adult livers were used as xenogeneic transplants in rats. The grafts were stored frozen for more than one year in liquid nitrogen. After thawing, they were evaluated histologically and for potential function for auxiliary liver support in 90%-hepatectomized rats. The efficacy of microporous polypropylene membrane as a macrocapsule for immunoprotection was also examined., Results: Frozen liver fragments could be preserved in liquid nitrogen for more than one year. Fetal fragments were better able to survive under the given conditions than the adult fragments. Macrocapsules protected the grafts from xenoantibodies. The survival rate of encapsulated fetal liver fragment-transplanted recipients on the seventh day after 90%-hepatectomy was 72%, while transplant recipients of fragments of fetal-liver, adult-liver, and encapsulated adult-liver, were 0, 0, and 0, respectively., Conclusions: Porcine fetal liver fragments survived longer in liquid nitrogen than did the adult ones. The fragments retained their capacity to provide auxiliary liver support in 90%-hepatectomized rats.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

Background: Reports on the relevance of immunogenetic factors in living donor adult liver transplantation (LDALT) are often conflicting or inconclusive. We therefore investigated the human leukocyte antigen (HLA) mismatches, lymphocyte crossmatch positivity, and the reactivity in mixed lymphocyte culture (MLC) in a series of LDALT., Methods: A total of 104 LDALT patients were studied. The minimum follow-up was 12 months, and the graft survival rates were assessed. The incidence of the most common complications was analyzed. And the influence of HLA, the flow cytometric analysis findings, enhanced cytotoxic cross-matching and MLC on graft survival, and acute rejection was also investigated., Results: As a result, 96 negative cross-matching and eight positive cross-matching cases were identified. Positive cytotoxic cross-matching had a significant effect on graft survival (P<0.05), while flow cytometric cross-matching also had an additional effect on acute rejection (P<0.05). The MLC of the patients with three HLA mismatches was significantly higher than the MLC of patients with zero HLA mismatches. The incidence of acute cellular rejection (ACR) was higher in the patients with three mismatches than in the other patients, and moderate rejection only occurred in the patients with three mismatches., Conclusion: HLA mismatching was not statistically associated with the overall graft survival after LDALT. The graft failure rates were higher in the positive cross-matching cases and therefore a strong immuosuppressant might be needed for positive cross-matching cases.

Background: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors., Methods: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA., Results: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months., Conclusions: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

Background: Bile leakage after living donor liver transplantation (LDLT) remains a serious problem, resulting in lower survival rates. The aim of this study is to clarify the benefits of in situ leakage testing of the cut surface of grafts in LDLT., Methods: A total of 135 LDLTs were analyzed. The patients were divided into the following two groups according to the in situ dye injection leakage test of the cut surface: test group (n=40) and control group (n=40). The incidence of bile leakage and the risk factors were identified by analyzing the recipients, donors, and transplantation variables., Results: Bile leakage occurred in 12.5% (10/80) of LDLTs. In the control group, there were nine cases of bile leakage (22.5%). On the other hand, there was only one case (2.5%) of bile leakage in the test group (P<0.05). The bile leakage case in the test group was resolved preservationally. However, 2 of the 9 (22.2%) bile leakage cases in the control group required surgery., Conclusion: Although there is biliary complication, especially bile leakage from the cut surface, as an inevitable consequence of LDLT, this study suggests that there is advantage in conducting bile leakage testing to minimize the incidence of bile leakage from the cut surface, which is associated with a high risk of graft failure.

Background: Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft., Methods: Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out., Results: The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9+/-5.5, 28.2+/-2.9, and 34.1+/-3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8+/-9.3 mg/dl in control group and 7.0+/-3.3 mg/dl in venoplasty group (P<0.05). Mean amount of ascites on POD 7 and 14 are 1576+/-1113 and 1397+/-1661 cc in control group, and 736+/-416 and 550+/-385 cc in venoplasty group, respectively (P<0.05). Two-year survival rate is 75.2 % in control group and 86.6 % in venoplasty group (P<0.05)., Conclusions: We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function.

The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E(1) (vasodilator and hepatoprotective effect; 500 microg/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome.

Background/aims: The practice of living-donor liver transplantation has been widely established. However, in adult cases, the issue of graft liver volume has been raised. Recently, liver transplantation using the right lobe has been done in cases requiring a larger graft volume. We compared right lobectomy with left lobectomy for hepatocellular carcinoma not accompanied by liver cirrhosis and examined the safety of hepatic right lobectomy for donation., Methodology: In total, 124 hepatocellular carcinoma patients without liver cirrhosis, 89 who had undergone right hepatectomy and 35 who had undergone left hepatectomy, were studied. For each group, we statistically examined the patients' profiles., Results: The resected right lobe was significantly heavier than the left lobe. There were significant differences between the two groups in terms of the number of blood transfusions needed. Moreover, delayed recoveries in terms of hemoglobin, total bilirubin, and clotting disorder on postoperative day 7, as well as the frequency of any complications, were more prevalent in the right-lobe group., Conclusions: It was confirmed that right lobectomy is more invasive than left lobectomy. It is necessary to prioritize the donor's safety and quality of life in living-donor liver transplantation, and adequate medical and ethical consideration is demanded.

Background/aims: While allogeneic organ transplantation has been performed safely, a major barrier in xenogeneic transplantation is how to inhibit hyperacute rejection., Methodology: We challenged xenogeneic fetal liver transplantation from pig to dog. The graft was investigated by immunohistochemical analysis on recipient's IgG, IgM and C3., Results: In 1 of 4 cases, the graft escaped hyperacute rejection for about 4 hours after transplantation, however, the recipient died next day due to hemorrhage from the torn capsule of the liver due to the arterial blood pressure of the recipient. Histologically, the parenchyma showed good countenance and no congestion nor hemorrhage was shown in the vessels. On immunohistochemical analysis, canine IgG, IgM and C3 were deposited on the sinusoidal epithelium of the fetal liver more moderately than that of adult control. Fetal porcine liver showed less expression of major histocompatability complex class I antigen than that of the adult one., Conclusions: We consider that the hyperacute rejection occurred more slowly in xenogeneic fetal liver transplantation than in the adult one due to not only less expression of major histocompatability complex class I, but also lower expression of the epitope recognized by a natural antibody of the recipient.

Serum soluble human leucocyte antigen (HLA) class-I is a useful marker for predicting immunological events in organ transplantation. In cadaver liver transplant cases it is especially the case that high amounts of soluble HLA-I are excreted from the grafts. In Japan, almost all liver transplants have been performed from living parent donors to their children. Therefore, it is interesting to know how soluble HLA-I changes in relation to clinical course. As part of this study we first examined serum concentrations of soluble HLA-I in 33 paediatric patients using enzyme-linked immunosorbent assay. Soluble HLA-I is composed of three different sized molecules (45, 39 and 34-36 kDa); then the change of distribution of these three molecules was demonstrated by Western blot analysis. When donor and recipient have different soluble HLA-I band patterns, the origin of the antigen can be assumed by this method. We found that in a comparison between pre- and post-transplants, the six out of eight (75%) patients that suffered episodes of acute rejection showed a significant elevation of soluble HLA-I, and all patients with infectious episodes had an elevated soluble HLA-I. Meanwhile, 10 out of 22 (45%) patients without any clinical complications still showed increased soluble HLA-I. The Western blot analysis showed that the soluble HLA-I molecules were considerably derived from the grafted liver, from one week to 24 months after grafting. In acute rejection, the band signals of donor origin were significantly increased. These signals were attenuated after immunosuppressive therapy. The grafted liver appears to contribute to the increase of soluble HLA-I following liver transplantation, and this increase is greater with the effects of the host immune system.

Acute liver failure caused by viral infection, surgical resection of a large part of the liver or by drug use has a high mortality. For its treatment, hepatocyte or liver tissue transplantation is useful. We report here the beneficial effects of xenogeneic fetal liver fragment (FLF) transplantation with an immunoisolation macrocapsule. The macrocapsules were made of a microporous polypropylene membrane. Pig FLFs (1 mL) was inserted into each capsule to serve as a graft in LEW rats. Acute liver failure was induced by 90% liver resection on day 0. Group 1: transplantation of encapsulated FLF into the omentum 2 days before liver resection (n = 17). Group 2: FLF transplantation into the omentum on day -2 (n = 11). Group 3: liver resection (control) (n = 19). The survival rate, the histology of the grafts and the biochemical parameters [blood sugar (BS), GPT, and GOT] were evaluated. The survival rates of groups 1, 2, and 3 on day 7 were 70.6, 0, and 11.1%, respectively. There were significant differences in BS, GPT, and GOT levels between groups 1 and 3 on day 1 (p < 0.05). On day 28, the histological analyses of the grafts of encapsulated FLFs revealed that the hepatocytes appeared viable, but that the haematopoietic cells had degenerated. Xenogeneic FLFs with macrocapsules survived more than 1 mo, and supported the host's liver function.

The survival of allogeneic fetal liver fragments in the omentum was analyzed in rats. The lymphocyte subsets of the spleen and peripheral blood were also examined. When the fetal liver fragments were transplanted into the omentum, they survived for 2 wk, whereas adult liver fragments survived only 1 wk. In fetal liver fragments transplantation, the CD8 positive lymphocyte percentage in peripheral blood decreased significantly 3 wk after transplantation in comparison with that in adult liver fragment transplantation. The skin graft of the donor party showed a longer median survival time in rats receiving fetal liver fragment transplants than that in recipients of adult liver fragments. Although further study is needed, allogeneic fetal liver fragments survived longer in the omentum than reported elsewhere, and the decrease of CD8 positive peripheral blood lymphocytes may have been the reason for this.

Isogeneic (rat) and xenogeneic (swine) fetal liver fragments (FLF) transplantation into the omentum was performed for D-galactosamine (D-Gal)-induced acute and carbon tetrachloride (CCl4)-induced chronic hepatic failure in rats. The recipients that had iso or xeno FLF showed higher survival rates than the nontransplanted controls on a lethal dose (2.6 g/kg body weight) of D-Gal (survival rates: Iso 70%, Xeno 80%, and control 9.1%). On a sublethal dose (1.0 or 1.2 g/kg) of D-Gal, iso, or xeno FLF caused marked improvement of the values of GPT, GOT, and total bilirubin (T.Bil); at 72 h after D-Gal injection they went significantly lower than those of controls (Iso vs. control; p < 0.01, Xeno vs. control; p < 0.05). Histological examination of the livers revealed severe damage in controls, however, only a slight damage was found in iso or xeno FLF transplanted rats. Iso grafts were fairly well preserved in the omentum at 72 h posttransplants, however, xeno graft had almost changed into a necrotic tissue. CCl4 was administered subcutaneously for 14 wk to induce chronic hepatic failure and then iso FLF were transplanted 3 days after the last CCl4 injection. Iso FLF transplanted rats showed higher improvement of GPT and GOT values at 12 days posttransplants compared with controls (GPT p < 0.01, GOT p < 0.05), although histological improvement was not so remarkable in both group. Iso grafts formed nodules with many hepatocytes in the omentum 12 days posttransplant. The results indicate that iso or xeno FLF transplantation could be an alternative approach for incurable liver insufficiencies.