Outcomes of liver transplantation using Hepatitis B core-positive liver grafts: Implications for prophylaxis

The number of patients listed for liver transplantation has outpaced the number of transplants that can be performed. This disparity between transplant candidates and the availability of donor grafts has led to an increase in mortality for patients waiting for liver transplantation. One strategy used to increase the donor pool has been the utilization of expanded donor grafts, such as those from donors with hepatitis B core antibody (anti-HBc). However, use of anti-HBc-positive grafts can potentially place the recipient at risk of de novo post-transplant hepatitis B virus (HBV) infection. The spectrum of liver disease from de novo hepatitis B ranges from mild hepatitis to graft loss. Fortunately, the risk of de novo HBV infection can be decreased with administration of oral nucleosides or nucleotides and hepatitis B immunoglobulin to the recipient. This review focuses on the epidemiology, natural history, and prophylactic strategies to reduce the risk of de novo hepatitis B in liver transplant recipients who receive anti-HBc-positive grafts.     

活体肝移植中非标准供肝的可用性分析

目的 了解活体肝移植非标准供肝受体的并发症及生存率,分析活体肝移植中非标准供肝的可用性.方法 四川大学华西医院肝移植中心2001年1月-2007年12月完成成人间活体肝移植并资料齐全的患者92例.比较不同供体年龄、性别配型、供肝脂肪变程度、移植物质量与受体体质量比(GRWR)、肝中静脉重建情况,患者术后6个月的生存率及并发症发生率.根据不同资料分别采用单因素方差分析、X2检验或Cpx回归分析.结果 使用脂肪变性≥30%供肝的4例受体术后都出现了不明原因的肝功能衰竭,均在观察时间内死亡,而脂肪变性＜30%的受体中,术后6个月生存率为91.7%.虽然GRWR＜0.8%的受体生存率(86.9%)与GRWR≥0.8%的受体生存率(87.8%)比较,差异无统计学意义(X2=0.022,P＞0.05),但小供肝组流出道的重建情况与其生存率相关(X2=10.612,P＜0.01).供体年龄是否≥50岁和供、受体性别是否配型等对术后6个月并发症及生存率的影响差异均无统计学意义(P＞0.05).Cox回归分析结果显示,供肝脂肪变性≥30%对生存率有较大的影响.结论 供肝脂肪变性程度是影响受体术后并发症及生存率的重要因素.而以往认为的GRWR＜0.8%现已不是绝对的禁忌标准,但必须保证小供肝受体流出道通畅.供体年龄≥50岁、交叉性别供肝对受体术后并发症及生存率无影响.     

Evaluation of donor hepatic iron concentration as a factor of early fibrotic progression after liver transplantation

BACKGROUND/AIMS: Hepatic iron may act as an important co-morbid factor in non-hemochromatotic liver diseases, but whether it may favour fibrogenesis after liver transplantation is not known. To verify whether the hepatic iron concentration of the graft might play a role in the rapid fibrotic progression frequently observed after liver transplantation for chronic hepatitis C. METHODS: The hepatic iron concentration, measured at the time of the donor operation, was retrospectively related to the histological follow-up data of 68 recipients (49 males, 19 females), of whom 38 were hepatitis C virus positive. RESULTS: The hepatic iron concentration in donor liver biopsies ranged from 25 to 7,100 microg/gdw. After a median follow-up of 19 months, nine patients (five HCV positive) had a staging score >3. There was a significant association between a higher frequency of increasing staging and donor age >50 years. In female HCV-positive recipients, a graft hepatic iron concentration >1,200 microg/gdw was associated with fibrosis progression >0.15 fibrosis units per month (4/4 vs. 1/7, p<0.01). CONCLUSIONS: The graft hepatic iron concentration may be one of the factors involved in early fibrosis progression due to recurrent hepatitis C in female recipients.     

Modified techniques for adult-to-adult living donor liver transplantation

BACKGROUND: Because of critical organ shortage, transplant professionals have utilized living donor liver transplantation (LDLT) in recent years. We summarized our experience in adult-to-adult LDLT with grafts of right liver lobe by a modified technique. METHODS: From January 2002 to August 2005, 24 adult patients underwent living donor liver transplantation with grafts of the right liver lobe at West China Hospital, Sichuan University, China. Twenty-two patients underwent modi-Bed procedures designed to improve the reconstruction of the right hepatic vein and the tributaries of the middle hepatic vein by interposing a great saphenous vein ( GSV) graft and the anastomosis of the hepatic arteries and bile ducts. RESULTS: No severe complications and death occurred in all donors. In the first 2 patients, (patients 1 and 2), operative procedure was not modified. One patient suffered from "small-for-size syndrome" and the other died of sepsis with progressive deterioration of graft function. In the rest 22 patients (patients 3 to 24), however, the procedure of venous reconstruction was modified, and better results were obtained. Complications occurred in 7 recipients including acute rejection (2 patients), hepatic artery thrombosis (1), bile leakage (1), intestinal bleeding (1), left sub-phrenic abscess (1), and pulmonary infection (1). One patient with pulmonary infection died of multiple organ failure (MOF). The 22 patients underwent direct anastomosis of the right hepatic vein to the inferior vena cava (IVC), 9 direct anastomosis plus the reconstruction of the right inferior hepatic vein, and 10 direct anastomosis plus the reconstruction of the tributaries of the middle hepatic vein by in-terpos-ing a GSV graft to provide sufficient venous outflow. Trifurcation of the portal vein was met in 3 patients. Venoplasty or separate anastomosis was performed. The ratio of graft to recipient body weight ranged from 0.72% to 1.17%. Among these patients, 19 had the ratio <1.0% and 4 <0.8%, and the ratio of graft weight to recipient standard liver volume was between 31.86% and 62.48%. Among these patients, 10 had the ratio <50% and 2 <40%. No "small-for-size syndrome" occurred in the 22 recipients who were subjected to modified procedures. CONCLUSIONS: With the modified surgical techniques for the reconstruction of the hepatic vein to obtain an adequate outflow and provide a sufficient functioning liver mass, living donor liver graft in adults using the right lobe can be safe to prevent the "small-for-size syndrome".     

Host factors are dominant in the development of post-liver transplant non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is a recognized problem in patients after orthotopic liver transplantation and may lead to recurrent graft injury. As the increased demand for liver allografts fail to match the available supply of donor organs, split liver transplantation (SLT) has emerged as an important technique to increase the supply of liver grafts. SLT allows two transplants to occur from one donor organ, and provides a unique model for observing the pathogenesis of NAFLD with respect to the role of recipient environmental and genetic factors. Here we report on two recipients of a SLT from the same deceased donor where only one developed non-alcoholic steatohepatitis (NASH), suggesting that host factors are critical for the development of NASH.     

Clinical study on safety of adult-to-adult living donor liver transplantation in both donors and recipients

AIM: To investigate the safety of adult-to-adult living donor liver transplantation (A-A LDLT) in both donors and recipients. METHODS: From January 2002 to July 2006, 50 cases of A-A LDLT were performed at West China Hospital, Sichuan University, consisting of 47 cases using right lobe graft without middle hepatic vein (MHV), and 3 cases using dual grafts (one case using two left lobe, 2 using one right lobe and one left lobe). The most common diagnoses were hepatitis B liver cirrosis, 30 (60%) cases; and hepatocellular carcinoma, 15 (30%) cases in adult recipients. Among them, 10 cases had the model of end-stage liver disease (MELD) with a score of more than 25. Donor screening consisted of reconstruction of the hepatic blood vessels and biliary system with 3-dimension computed tomography and volumetry of whole liver and right liver volume. Various improved surgical techniques were adopted in the procedures for both donors and recipients . RESULTS: Forty-nine right lobes and 3 left lobes (2 left lobe grafts for 1 recipient, 1 left lobe graft for 1 recipient who had received right lobe graft donated by relative living donor) were obtained from 52 living donors. The 49 right lobe grafts, without MHV, weighed 400 g-850 g (media 550 g), and the ratio of graft volume to recipient standard liver volume (GV/SLV) ranged from 31.74% to 71.68% (mean 45.35%). All donors' remnant liver volume was over 35% of the whole liver volume. There was no donor mortality. With a follow-up of 2-52 mo (media 9 mo), among 50 adult recipients, complications occurred in 13 (26%) cases and 4 (8%) died postoperatively within 3 mo. Their 1-year actualsurvival rate was 92%. CONCLUSION: When preoperative CT volumetry shows volume of remnant liver is more than 35%, the ratio of right lobe graft to recipients standard liver volume exceeding 40%, A-A LDLT using right lobe graft without MHV should be a very safe procedure for both donors and recipients, otherwise dual grafts liver transplantation should be considered.     

Copper metabolism after living related liver transplantation for Wilson＇s disease

AlM: Liver transplantation is indicated for Wilson's disease(WD) patients with the fulminant form and end-stage liverfailure. The aim of this study was to review our experiencewith living-related liver transplantation (LRLT) for WD.METHODS: A retrospective review was made for WDundergoing LRLT at our hospital from January 2001 toFebuary 2003.RESULTS: LRLT was carried out in 15 patients with WD,one of them had fulminant hepatic failure and the others had end-stage hepatic insufficiency. The mean age of the patients was 14.5±2.5 years (range 6 to 20 years). All the recipients had low serum ceruloplasmin levels with a mean value of 126.8±34t.8 mg/L before transplantation. The serum ceruloplasmin levels increased to an average of 238.6±34.4mg/L after LRLT at the latest evaluation, between 2 and 27months after transplantation. A marked reduction in urinary copper excretion was observed in all the recipients after transplantation. Among the eight recipients with preoperative Kayser-Fleischer (K-F) rings, this abnormality resolved completely after LRLT in five patients and partially in three.All the recipients are alive and remain well, and none has developed signs of recurrent WD after a mean follow-up period of 15.4±9.3 months (range 2-27 months) except one who died of severe rejection. The donors were 14t mothers and 1 father. The serum ceruloplasmin levels were within normal limits in all the donors (mean: 220±22.4 mg/L). The mean donor age was 35.0±4.0 years (range, 30 to 45 years).Two donors had biliary leakage and required reoperation.Grafts were harvested as follows: four right lobe grafts without hepatic middle vein and eleven left lobe grafts with hepatic middle vein. The grafts were blood group-compatible in all recibents. Two patients had hepatic artery thrombosis and underwent retransplantation.CONCLUSION: LRLT is a curative procedure in Wilson's disease manifested as fulminant hepatic failure and/or endstage hepatic insufficiency. After liver transplantation, the serum ceruoplasmin level can increase to its normal range while urinary copper excretion decreases. Grafts chosen from heterozygote carriers do not appear to confer any risk of recurrence in recipients.     

Decreased liver hepcidin expression in the Hfe knockout mouse

Hepcidin is a circulating antimicrobial peptide which has been proposed to regulate the uptake of dietary iron and its storage in reticuloendothelial macrophages. Transgenic mice lacking hepcidin expression demonstrate abnormalities of iron homeostasis similar to Hfe knockout mice and to patients with HFE-associated hereditary hemochromatosis (HH). To identify any association between liver hepcidin expression and the iron homeostasis abnormalities observed in HH, we compared liver hepcidin mRNA content in wild type and Hfe knockout mice. Because the iron homeostasis abnormalities in the Hfe knockout mice are greatest early in life, we analyzed mice at different ages. At four weeks of age, Hfe knockout mice had significantly decreased liver hepcidin mRNA expression compared to wild type mice. The decreased hepcidin expression was associated with hepatic iron deposition, elevated transferrin saturations, and decreased splenic iron concentrations. At 10 weeks of age, despite marked hepatic iron loading, Hfe knockout mice demonstrated liver hepcidin mRNA expression similar to that observed in wild type mice. Placing 8 week-old wild type and Hfe knockout mice on a 2% carbonyl iron diet for 2 weeks led to a similar degree of hepatic iron loading in each group. However, while the wild type mice demonstrated a mean five-fold increase in liver hepcidin mRNA, no change was observed in the Hfe knockout mice. The lack of an increase in liver hepcidin expression in these iron-loaded Hfe knockout mice was associated with sparing of iron deposition into the spleen. These data indicate that the normal relationship between body iron stores and liver hepcidin mRNA levels is altered in Hfe knockout mice, such that liver hepcidin expression is relatively decreased. We speculate that decreased hepcidin expression relative to body iron stores contributes to the iron homeostasis abnormalities characteristic of HH.     

Personal experience with the procurement of 32 liver allografts

AIM: To introduce the American Pittsburgh's method of rapid liver procurement under the condition of brain death and factors influencing the quality of donor liver. METHODS: To analyze 32 cases of allograft liver procurement retrospectively and observe the clinical outcome of orthotopic liver transplantation. RESULTS: Average age of donors was 38.24±12.78 years, with a male:female ratio of 23:9. The causes of brain death included 21 cases of trauma (65.63%) and nine cases of cerebrovascular accident (28.13%). Fourteen grafts (43.75%) had hepatic arterial anomalies, seven cases only right hepatic arterial anomalies (21.88%), five cases only left hepatic arterial anomalies (15.63%) and two cases of both right and left hepatic arterial anomalies (6.25%) among them. Eight cases (57.14%) of hepatic arterial anomalies required arterial reconstruction prior to transplantation. Of the 32 grafts evaluated for early function, 27 (84.38%) functioned well, whereas three (9.38%) functioned poorly and two (6.25%) failed to function at all. Only one recipient died after transplantation and thirty-one recipients recovered. Four recipients needed retransplantation. The variables associated with less than optimal function of the graft consisted of donor age (35.6±12.9 years vs 54.1±4.3 years, P<0.05), duration of donor's stay in the intensive care unit (ICU) (3.5±2.4 d vs 7.4±2.1 d, P<0.005), abnormal graft appearance (19.0% vs 100%, P<0.05), and such recipient problems as vascular thromboses during or immediately following transplantation (89.3% vs 50.0%, P<0.005). CONCLUSION: During liver procurement, complete heparization, perfusion in situ with localized low temperature and standard technique procedures are the basis ensuring the quality of the graft. The hepatic arterial anomalies should be taken care of to avoid injury. The donor age, duration of donor's staying in ICU, abnormal graft appearance and recipient problem are important factors influencing the quality of the liver graft.     

Cytomegalovirus infection after liver transplantation in children

Post-liver transplant cytomegalovirus (CMV) infection (seroconversion or virus isolation) and CMV disease (infection plus clinical signs and symptoms) were studied in relation to pretransplant recipient and donor serology, age, nutritional status and the effect of paediatric versus adult (reduced size) grafts. Of 70 children receiving 79 transplants, 26 (37%) had evidence of CMV infection, and eight (11.5%) had evidence of CMV disease, four of whom died. The primary infection rate (where the recipients were CMV negative) was 71% with mortality of 7% with most receiving a CMV-positive graft. The active secondary infection rate (reactivation or reinfection, where the recipients were CMV positive) was 60% with mortality of 12.5%. No significant differences in infection or disease rates were found comparing malnourished versus well-nourished patients, or between those who received whole or reduced-size grafts. The high prevalence of CMV infections supports the view that clinical signs alone are inadequate to direct investigations for CMV. Both primary and active secondary CMV infection can result in serious morbidity and mortality in children receiving liver transplants. These data do not support the strategy of providing immunoprophylaxis to seronegative recipients only, at least in paediatric liver transplantation.     

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.     

Living donor liver transplantation: issues regarding left liver grafts

BackgroundThe necessity of widening the indications for living donor liver transplantation (LDLT) has been emphasised. Clarification of the advantages and limitations of using a left liver graft for LDLT in adults is essential for donor safety.MethodsBetween June 1990 and November 2002, 185 patients underwent LDLT at Shinshu University Hospital, Japan. In 97 of these, the graft comprised the left liver with or without the left portion of the caudate lobe. The peri-hepatectomy profiles of the donors, significance of left liver grafts, postoperative courses of the donors and recipients, and survival of the recipients were investigated.ResultsAll the donors recovered well and returned to a normal lifestyle. None required banked-blood transfusion or repeat surgery, and postoperative liver function tests had satisfactory results. The cold ischaemic time for the graft was 127±54 minutes. The graft volumes (GVs) ranged from 230 to 625 ml, and GV/standard liver volume (SV) ratios varied from 22% to 65%, at the time of transplantation. Although 85% of the liver grafts had GV/SV ratios <50%, no patient developed immediate postoperative liver failure. Patient survival rates were 89%, 84% and 84% at 1, 3 and 5 years, respectively.DiscussionAlthough LDLT using a left liver graft imposes potential postoperative complications (a small liver is more vulnerable to injury, and recipients of small grafts are at higher risk of complications during recovery), such grafts have yielded acceptable results in adult LDLT, with minimal burden to the donors.     

First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50‐year‐old woman who had undergone living donor liver transplantation at the age of 38 years for management of post‐partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End‐stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno‐venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.     

Middle hepatic vein reconstruction of graft for a patient with intrahepatic portosystemic shunt

Middle hepatic vein reconstructions for modified right liver grafts in living donor liver transplantation provide satisfactory results. We report a patient who had undergone transjugular intrahepatic portosystemic shunt before living donor liver transplantation, in which the middle hepatic vein was reconstructed using a preserved great saphenous vein. A 41-year-old Japanese man with a 5-year history of alcoholic liver cirrhosis and esophageal varices was admitted to our hospital for living donor liver transplantation. He had undergone endoscopic variceal ligations and transjugular intrahepatic portosystemic shunt for esophageal variceal bleeding, and ascites. He had living donor liver transplantation, which was performed using his sister's right lobe without the middle hepatic vein. The recipient's estimated standard liver volume calculated by abdominal computer-assisted tomography was 1166 mL. The exact weight of the donor's right lobe was 507 g, which was equivalent to 44% of the recipient's standard liver volume. At bench surgery, the middle hepatic vein was reconstructed using a preserved great saphenous vein, which was cut in 2 strips to make a thicker tube graft by suturing, and subsequently, the newly made tube graft end was anastomosed to V5 and V8 branches of the graft. The metallic stent for transjugular intrahepatic portosystemic shunt buried in the recipient's right hepatic vein was removed with the right hepatic vein. The other end of the saphenous tube graft was anastomosed to the right anterior aspect of the vena cava. Stumps of the middle and left hepatic veins were oversewn. Postoperative blood flow in the graft and the reconstructed hepatic veins has been satisfactory with normal liver functions.     

Isolated intestinal transplantation for intestinal failure

OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal failure. However, some experience life-threatening complications from parenteral nutrition, and in these individuals intestinal transplantation may be lifesaving. METHODS: This is a retrospective review of 28 consecutive isolated small bowel transplants performed in eight adults and 20 children between December 1993 and June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient and graft survivals were 93% and 71%, respectively. The causes of graft loss were hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n = 1), and patient death (n = 1). The median length of time required until full enteral nutrition was 27 days. All 28 patients have experienced acute rejection of their small bowel grafts and rejection led to graft failure in five. Jaundice and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and hyperbilirubinemia was completely reversed in all patients with functional grafts within 4 months of transplantation. Three patients developed post-transplant lymphoproliferative disease (11%). Three recipients developed cytomegalovirus enteritis and all were successfully treated. CONCLUSIONS: Patient survival after intestinal transplantation is comparable to parenteral nutrition for patients with intestinal failure. Better immunosuppressive regimens are needed to decrease the risk of graft loss from acute rejection. The incidence of posttransplant lymphoproliferative disorder is higher after intestinal transplantation than after other solid organ transplants and the risk of cytomegalovirus enteritis is low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the absence of established cirrhosis can be reversed.     

Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission: a comparison with allografts from adult unrelated donors

Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.     

Desferrioxamine therapy accelerates clearance of iron deposits after bone marrow transplantation for thalassaemia

We treated 18 heavily iron-loaded patients who had become ex-thalassaemics after bone marrow transplantation with subcutaneous desferrioxamine therapy for 5-20 months. As determined using serum ferritin concentration, transferrin saturation and stainable liver iron obtained in follow-up biopsies, marked decreases in body iron stores were observed with this regimen. Moreover, the liver function tests demonstrate a trend to normalization in all cases. Local skin reactions to desferrioxamine were the only toxicities observed. We conclude that pharmacological iron chelation is a safe and effective therapy in the reduction of iron deposits in this clinical situation; it therefore represents a valid alternative to phlebotomy in selected patients.     

Anterior segment congestion of a right liver lobe graft in living-donor liver transplantation and strategy to prevent congestion

Background/Purpose. A left lobe graft from a small donor will not usually fulfill the metabolic demands of a larger recipient in adult-to-adult living-donor liver transplantation (LDLT). One solution to this problem is to use a right lobe graft. However, the necessity of middle hepatic vein (MHV) outflow drainage from the anterior segment (AS) of a right lobe graft has not yet been clearly described in the literature. From July 1997 to February 1998, five right lobe grafts without MHV outflow drainage were implanted in five adult recipients. The graft weights ranged from 650 to 1000?g, and their volumes ranged from 48% to 83% of the ideal liver mass of the recipients. Two grafts showed severe congestion of the AS immediately after reperfusion, followed by prolonged massive ascites and severe liver dysfunction in each patient postoperatively. Eventually, one patient died of sepsis, on posttransplant day 20, demonstrating progressive hepatic dysfunction. Methods. Subsequently, since March 1998, 176 of 208 adult recipients who received a right lobe graft, while demonstrating sizable (greater than 5-mm diameter) MHV tributaries underwent reconstruction of MHV outflow drainage, using the recipient's own autogenous or cryopreserved cadaveric interposition vein grafts. Results. In 170 of the 176 recipients, AS congestion was not demonstrated on enhanced liver computerized tomography (CT) or Doppler ultrasonography (USG) postoperatively, and the patency rate of interposition vein grafts was 96.6% on day 30 posttransplant. Conclusions. A right lobe graft without MHV outflow drainage might result in severe congestion of the AS, which could lead to the patient's death in an extreme situation. Preservation of MHV outflow drainage in a right lobe graft is possible by two harvesting methods: an extended right lobe (ERL) graft, in which the MHV trunk is included in the graft, and a modified right lobe (MRL) graft, in which venous tributaries of the MHV are reconstructed via interposition vein grafts into the recipient's hepatic venous system. From the viewpoint of donor safety, the ERL graft increases the donor's risk more than the MRL graft, because the remaining left liver lobe of the donor does not possess an MHV. Here, we introduce our experiences of MRL grafts in adult-to-adult LDLTs.     

Combined neonatal blood transplants in a parent-to-F1 mouse model: improved survival rates and stable long-term engraftment

The use of cord blood (CB) transplantation for adult patients is limited by the relatively low cell content of a single collection. Two, partially-matched CB grafts could provide optimal cell doses. The interactions among the donor-derived populations have not been fully evaluated. We used our mouse model (Neonatal peripheral blood--NPB--transplants to adult recipients) to evaluate whether grafts from two histocompatibility-disparate donors ("combined" grafts) had higher survival and faster hematopoietic recovery than single donor transplants, each at suboptimal cell dose (leading to survival <60%). Transplants were performed in a parent-to-F1 setting: NPB or bone marrow (BM) cells from the fully mismatched, homozygous parental strains (A/J, B6) were given to myeloablated B6AF1 recipients. Outcomes improved by combining NPB grafts: 48% of A/J graft recipients (1 x 10(6) cells/animal) survived; all animals transplanted with B6 (same cell dose) died. Survival after combined NPB transplants was 75% (P < 0.01) and recipients had accelerated recovery of WBCs and platelets compared to single donor A/J grafts (P < 0.01). No such improvements occurred with suboptimal dose combined BM transplants. Recipients of combined NPB grafts reconstituted with one donor primarily. Chimerism levels remained stable. Successful secondary transplants demonstrated long-term persistence of both NPB grafts. Combined haplo-identical NPB but not BM grafts, each transplanted at suboptimal cell doses, engraft synergistically leading to faster reconstitution. Although the mouse model does not fully represent the complex clinical aspects of human transplantation, our findings support the concept of using two CB grafts for adult patients when a sufficiently large single one is not available.     

Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts

AIM:To investigate the outcome of living donor liver transplantation(LDLT)recipients transplanted with small-for-size grafts(SFSGs).METHODS:Between November 2001 and December2010,196 patients underwent LDLT with right lobe liver grafts at our center.Recipients were divided into 2 treatment groups:group A with an actuarial graft-to-recipient weight ratio(aGRWR)<0.8%(n=45)and group B with an aGRWR≥0.8%(n=151).We evaluated serum liver function markers within 4 wk after transplantation.We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients,the donors and the transplantation procedures based upon a review of their medical records.RESULTS:Small-for-size syndrome(SFSS)developed in 7 of 45 patients(15.56%)in group A and 9 of 151patients(5.96%)in group B(P=0.080).The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation,albeit not significantly.The cumulative 1-,3-and 5-year liver graft survival rates were 82.22%,71.11%and 71.11%for group A and 81.46%,76.82%,and 75.50%for group B patients,respectively(P=0.623).However,univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival(P<0.001).Furthermore,multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival.CONCLUSION:Our study suggests that LDLT recipients with an aGRWR<0.8%may have liver graft outcomes comparable to those who received larger size grafts.Further studies are required to ascertain the safety of using SFSGs.