Relevance of HLA compatibility in living donor liver transplantation: the double‐edged sword associated with the patient outcome

HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA‐A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host‐versus‐graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft‐versus‐host disease (GVHD) was also analyzed. No recipients with recipient‐against‐donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with “R→D MM 0” together with “donor‐against‐recipient MM 3” died of fatal GVHD. HLA compatibility in LDLT not only affected the long‐term acceptance of graft livers but also the risk of fatal GVHD.     

Endovascular management of early hepatic artery thrombosis after living donor liver transplantation

To study the feasibility of endovascular management of early hepatic artery thrombosis (HAT) after living‐donor liver transplantation (LDLT) and to clarify its role as a less invasive alternative to open surgery. A retrospective review of 360 recipients who underwent LDLT. Early HAT developed in 13 cases (3.6%). Diagnosis was performed using Doppler, CT angiography, and digital subtraction angiography. Intra‐arterial thrombolysis (IAT) was performed using streptokinase or tPA. In case of underlying stricture, PTA was attempted. If the artery did not recanalize, continuous infusion was performed and monitored using Doppler US. Initial surgical revascularization was successful in 2/13 cases. IAT was performed in 11/13 cases. The initial success rate was 81.8% (9/11), the failure rate was 18.2% (2/11). Rebound thrombosis developed in 33.3% (3/9). Hemorrhage developed after IAT in 2/11 cases (18.2%). Definite endovascular treatment of HAT was achieved in 6/11 cases (54.5%) and definite treatment (surgical, endovascular or combined) in 9/13 cases (69%). (Follow‐up 4 months–4 years). Endovascular management of early HAT after LDLT is a feasible and reliable alternative to open surgery. It plays a role as a less invasive approach with definite endovascular treatment rate of 54.5%.     

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.     

Use of middle hepatic vein in right lobe living donor liver transplantation

The harvesting of the middle hepatic vein (MHV) with the right lobe graft for living‐donor liver transplantation allows an optimal venous drainage for the recipient; however, it is an extensive operation for the donor. This is a prospective, nonrandomized study evaluating liver functions and early clinical outcome in donors undergoing right hepatectomy with or without MHV harvesting. From August 2005 to July 2007, a total of 100 donor right hepatectomies were performed with (n = 49) or without (n = 51) the inclusion of the MHV. The decision to take MHV was based on an algorithm that considers various donor and recipient factors. There was no donor mortality in donors in either group. Overall complication rate was higher in MHV (+) donor group, however when remnant liver volume was kept above 30%, complication rates were similar between the groups. The results of this study show that right hepatectomy including the MHV neither affects morbidity nor impairs early liver function in donors when remnant volume is kept above 30%. The decision, therefore, of the extent of right lobe donor hepatectomy should be tailored to the particular conditions considering the graft quality and metabolic demand of the recipient.     

Chronic renal outcome after living donor liver transplantation

Chronic kidney disease (CKD) is one of the common complications after deceased donor liver transplantation. Although the worldwide pressing shortage in deceased donors has directed attention to living donor liver transplantation (LDLT), LDLT cohort data focusing on chronic renal dysfunction is limited. A total of 280 adult LDLT recipients (median 49 yr, 156 men) at the University of Tokyo hospital between 1996 and 2006 were reviewed. A total of 224 pre‐transplant liver failure patients (80.0%) showed an estimated glomerular filtration rate (eGFR) of more than 60 mL/min/1.73 m². However, during follow‐up at a mean of 1222 d after transplantation, eGFR declined to 60 mL/min/1.73 m² and 30 mL/min/1.73 m² in 150 (53.2%) and 21 (7.5%), respectively, and four patients (1.4%) required maintenance renal replacement therapy. Multivariate Cox proportional hazard model regression analysis revealed that recipient age (HR, 3.42 per 10‐yr increment; p < 0.001) and pre‐transplant eGFR (HR, 0.85 per 10‐mL/min/1.73 m² increment; p = 0.04) were associated independently with a post‐transplant decrease in eGFR to less than 30 mL/min/1.73 m². We conclude that higher age and lower pre‐transplant eGFR of an LDLT recipient indicate a high likelihood of subsequent development of advanced CKD. Preventive or therapeutic intervention should be optimized for these high‐risk patients.     

Clinical significance of gastrointestinal bleeding after living donor liver transplantation

The clinical presentations of gastrointestinal bleeding (GIB) occurring after living donor liver transplantation (LDLT) have not been fully described. We performed a retrospective analysis of 297 LDLT cases. Nineteen patients (6.4%) experienced GIB after LDLT. The etiology of GIB included bleeding at the jejunojejunostomy following hepaticojejunostomy (n = 13), peptic ulcer disease (n = 2), portal hypertensive gastropathy (n = 2), and other causes (n = 2). Hemostasis was achieved in 13 patients (68.4%) by endoscopic (n = 3), surgical (n = 1), or supportive treatments (n = 15), but not in the other six patients. Graft dysfunction (P < 0.001), hepaticojejunostomy (P = 0.01), portal vein pressure at the end of surgery >20 mmHg (P = 0.002), and operative blood loss >10 L (P = 0.004) were risk factors. One‐year graft survival rate was significantly lower in patients with GIB than in patients without GIB (P < 0.001). The inhospital mortality rate was 52.6% for patients with GIB, 75.0% for patients with graft dysfunction, and 14.3% for patients without graft dysfunction (P = 0.028). Despite its infrequency after LDLT, GIB has strong correlation with graft dysfunction and inhospital mortality.     

采用不含肝中静脉的右半肝行成人间活体肝移植

目的探讨采用不含肝中静脉的右半肝行成人间活体肝移植的可行性及安全性。方法2002年1月至2005年8月,我院施行了16例成人间右半肝活体肝移植,术中采用了不含肝中静脉的右半肝移植物,同时进行了一系列改良的手术技术包括肝右静脉的重建,右肝下静脉的重建,肝中静脉分支的搭桥等改进。结果全组供者无严重并发症及死亡。前2例受者中,1例发生肝静脉吻合口狭窄,1例因发生小肝综合征,死于肝功进行性恶化。后14例受者中发生并发症5例:急性排斥反应,肝动脉栓塞,胆漏,左膈下脓肿及肺部感染各1例;1例再移植术后肺部感染死于MODS。14例中除肝右静脉与下腔静脉(IVC)直接吻合外,其中5例加行右肝下静脉重建,另5例采用自体大隐静脉搭桥行肝中静脉分支与IVC重建,保证了右肝的流出道通畅。移植物与受者重量比(GRWR)为0.72%~1.15%,11例<1.0%,其中2例<0.8%,无小肝综合征发生。结论采用了改进的手术技术,特别是肝静脉流出道的充分重建可有效的避免小肝综合征,从而使采用不含肝中静脉的活体右半肝移植成为安全可靠的手术方式。     

异基因骨髓移植后合并感染30例临床分析

目的：分析异基因骨髓移植（allo-BMT）后感染的发生情况.方法：回顾性分析2008年6月-2009年6月30例allo-BMT患者的临床资料.患者均经过移植前预处理、移植物抗宿主病（GVHD）和感染的预防性治疗.移植后感染患者经验性给予抗细菌、抗真菌、抗病毒及抗结核治疗.结果：30例患者发生感染并发症33例次.由一种病原菌引起的感染21例次,其中细菌性感染10例次,间质性肺炎2例次,真菌感染5例次,肺结核1例次,带状疱疹3例次;≥2种病原所致的感染并发症12例次.患者均伴有不同程度的GVHD.3例GVHDⅢ～Ⅳ级患者因肺部混合感染导致死亡,其余治疗后好转.结论：混合感染仍是骨髓移植最常见的并发症,并与GVHD的发生相关.     

Clinical analysis of emergency liver transplantation: the role of living donor liver transplantation

The current liver allocation system requires reevaluation because of the advancements in peri‐transplantation care and surgical techniques. And, the role of living donor liver transplantation (LDLT) in an emergency has not been determined yet. Retrospective review of all patients undergoing emergency liver transplantation (LT) from January 2000 to June 2010 was conducted, and clinical data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver, and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT). The overall hospital mortality was 21.7% (15/69). The leading cause of death after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that a model for end‐stage liver disease (MELD) >33 [hazard ratio (HR), 16.6; 95% confidence interval (CI), 1.443–191.632; p = 0.024] and existence of pre‐transplantation intubation (HR, 18.2; 95% CI, 1.463–225.483; p = 0.024) were independent factors associated with poor survival after emergency LT. LDLT group and DDLT group showed no difference in hospital mortality (p = 0.854) and graft survival (p = 0.861). Thus, MELD score and respiratory insufficiency could be parameters predicting post‐transplant survival. And, LDLT using the right liver could be an appropriate alternative to DDLT in an emergency.     

成人活体肝移植

活体肝移植（LDLT）最初作为一种降低等待做肝移植患者死亡率的方法。日本京都大学LDLT开始于1990年6月,移植例数逐年增加,临床应用范围从小儿扩展到成人。肝脏右叶移植物的应用在LDLT具有重要临床意义,已经成为成人间LDLT标准方法。由于肝脏右叶移植物在LDLT移植后成功应用,近年来成人LDLT例数显著增加,自1990年6月至2005年12月,京都大学附属病院已完成了1140例LDLT手术,其中包括477例成人LDLT手术（年龄大于18岁）。HBV和HCV相关性肝硬化和肝癌是LDLT最常见的适应证,截至2005年12月,随访统计结果表明成人LDLT术后总的5年生存率为69．1％。     

活体肝移植进展与展望（2000-2020）

活体肝移植比公民逝世后器官捐献肝移植操作更为复杂,围手术期评估及技术实施直接影响供体安全和受体预后。目前,行活体肝移植时,供体选择应遵循“自愿、知情、无害”伦理原则,利用影像学评估供肝质量、解剖结构及残肝体积;受体选择时优先考虑良性终末期肝病病人,而选择肝癌病人应考虑肿瘤分期;移植物选择应满足不同受体的“移植物-受体重量比”标准,对于<3岁的儿童,其比值在2%~4%为宜;在传统开放手术供肝获取经验基础上,腹腔镜供肝获取技术发展与挑战并存;术中各管道重建时,管道条件、匹配程度及通畅性是移植技术的关键;供受体血型不相容时,应用利妥昔单抗可起到减少并发症及改善预后作用;术后精细化管理,尽量减少免疫抑制剂用量以期减少其药物相关副反应。尽管存在诸多问题,相信随着外科技术的进步,医生对肝脏解剖认识的加深及移植物再生血流动力学的理解,活体肝移植技术会更加完备、更加安全。作为公民逝世后器官捐献肝移植的重要补充,活体肝移植将为更多终末期肝病病人提供有效治疗手段。     

Surgical rationalization of living donor liver transplantation by abolition of hepatic artery reconstruction under a fixed microscope

The small diameter of the hepatic artery is one of the complexities of living donor liver transplantation (LDLT). We analyzed whether the direct suture technique using surgical loupes can simplify the operative process for LDLT compared with fixed microscopic reconstruction. We applied the direct technique to rationalize the operative process and abolished routine microsurgery from 2004. Two hundred and nine LDLT with a postoperative period over 34 months were carried out from 1996 to 2008. The patients were divided into two groups: the micro group (children: 20, adults: 72) and the non‐micro group (children: 12, adults: 97). Running anastomosis was undertaken in the non‐micro group. The anastomotic size of the children was significantly smaller than that of the adults, but larger than 2 mm (2.38 ± 0.4 vs. 2.7 ± 0.47 mm, p = 0.0005). By appropriate choice of the proximal artery, direct anastomosis is possible even in children. Early complications occurred in seven cases in the micro group, but none occurred in the non‐micro group (p < 0.05). Significant reductions were observed in operation time (p < 0.0001), blood loss (p < 0.05), and hospital stay (p < 0.01) in the non‐micro group. Non‐microscopic anastomosis is useful for the rationalization of LDLT.     

Association of thrombocytopenia with outcome following adult living donor liver transplantation

This study aimed to evaluate the association of postoperative thrombocytopenia with outcome following adult living donor liver transplantation (LDLT) for end‐stage liver disease (ESLD). It was a prospective study of 120 consecutive adult LDLT from September 2012 to May 2015. Preoperative platelet counts (PLTs) and postoperative PLTs were recorded at regular intervals till 3 months after LDLT. Univariate and multivariate analyses were performed. The median pretransplant PLT was 61 × 10⁹/l. The lowest median PLT after LDLT was observed on POD 3. Patients were stratified into low platelet group (n = 83) with PLT <30 × 10⁹/l and high platelet group (n = 37) with PLT ≥30 × 10⁹/l. Patients with PLT <30 × 10⁹/l had statistically significant higher grade III/IV complication (P = 0.001), early graft dysfunction (P = 0.01), sepsis (P = 0.001), and prolonged ascites drainage (P = 0.002). On multivariate analysis, PLT<30 × 10⁹/l was identified as an independent risk factor for grade III/IV complications (P = 0.005). Overall, patients survival was significantly different between two groups (P = 0.04), but this predictive value was lost in patients who survived more than 90 days (P = 0.37). Postoperative PLT of <30 × 10⁹/l was a strong predictor of major postoperative complications and is associated with early graft dysfunction, prolonged ascites drainage, and sepsis. The perioperative mortality rate was high in the thrombocytopenia group.     

Ten years survival with excellent outcome after living donor liver transplantation from 70 years old donor for primary hepatic neuroendocrine carcinoma: Case report

BACKGROUNDPrimary hepatic carcinoid tumors (PHCT) are rare entities; they are even rarer than extrahepatic neuroendocrine gastrointestinal tumors with only about 95 cases reported in the literature. An extrahepatic primary tumor must be excluded to confirm the diagnosis of PHCT.CASE PRESENTATIONWe report a case of a 42-year-old male patient with a primary hepatic neuroendocrine carcinoma, who successfully underwent living donor liver transplantation from his 70 years old mother with 10 years follow-up. Both donor and recipient are still alive and in the good health.CONCLUSIONLiving liver donation from elderly donors for the patients with irresectable neuroendocrine liver malignancies can be as safe as deceased donation or liver donation from young donors (age < 50). Living donation from elderly donors might significantly expand the donor pool for patients with liver neuroendocrine tumors (NET) and potentially reduce waiting list mortality. Especially young patients with irresectable NET can benefit from this option. However, case–control studies are needed to verify the advantage of living liver transplantation (LDLT) for the patients with irresectable liver NET and to define selection criteria for these patients.     

The impact of meticulous management for hepatic artery thrombosis on long‐term outcome after pediatric living donor liver transplantation*

Abstract: To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long‐term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One‐ and 10‐yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft‐to‐recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S‐group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M‐group, n = 13). One patient underwent re‐LDLT. One‐ and five‐yr patient survival rates were 83% and 83% in the S‐group, and 77% and 77% in the M‐group (p = n.s.). The incidence of biliary complications in the S‐group (58%) was significantly higher than that of the M‐group (15%). For a successful long‐term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.     

Evaluation of graft stiffness using acoustic radiation force impulse imaging after living donor liver transplantation

Acoustic radiation force impulse (ARFI) imaging is an ultrasound‐based modality to evaluate tissue stiffness using short‐duration acoustic pulses in the region of interest. Virtual touch tissue quantification (VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation (LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post‐LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume‐to‐recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post‐LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT.