改善胆管微循环是预防肝移植术后缺血型胆道病变的重要措施

原位肝移植已成为治疗终末期肝病的主要手段，患者5年生存率可达80％以上。但胆道并发症尤其是缺血型胆道病变（ischemic—type biliary lesions，ITBL）已成为影响患者长期生存和生活质量的重要因素。ITBL是指肝移植术后由各种因素（不包括肝动脉栓塞）引起的胆管动脉损害所产生的缺血型胆管炎，发生率为5％-15％。ITBL的病因目前尚不清楚，一般认为与冷、热缺血性损伤、缺血再灌注损伤、免疫因素、巨细胞病毒感染等有关。     

肝移植手术相关并发症的防治

目的总结和探讨原位肝移植手术相关并发症发生的原因、预防及治疗。方法对1993年4月至2004年12月所实行的647例次原位肝移植患者的临床资料进行回顾性分析。结果肝移植手术后共发生并发症73例,发生率11．3％（73／647）,包括血管并发症39例（6．0％,39／647）,其中肝动脉23例（3．6％）,门静脉6例（0．9％）,腔静脉10例（1．5％）,其中腔静脉并发症均发生在非腔静脉整形患者;放置内支架治疗肝动脉狭窄2例,均成功;肝动脉血栓形成者行再次移植治疗,成功率为4／6,再血管化和气囊扩张成功率分别为3／7和2／7;放置内支架治疗门静脉吻合口狭窄和腔静脉狭窄的成功率为3／3和10／10。发生胆道并发症34例（5．3％）,其中放置T管患者发生胆道并发症27例,未放置T管患者7例,两组吻合口胆漏、胆道狭窄和感染的发生率比较,差异有统计学意义（P〈0．01）。结论传统背驮式肝移植术能有效预防腔静脉并发症的发生;放置内支架技术治疗血管狭窄性病变效果好;早期肝动脉血栓形成应采取再次肝移植;确保供肝胆道系统的血供是减少胆道并发症的关键;不放置T管的胆管端端吻合术,是胆道重建的首选术式。     

肝移植术后细菌性感染的病原学特征及分布特点

目的研究肝移植术后细菌感染的流行病学规律。方法回顾性分析451例患者原位肝移植术后细菌学资料。结果肝移植术后239例患者出现细菌感染,细菌感染率为53．0％,共分离出菌株304株,其中革兰阳性（G^＋）球菌占59．9％（182／304）,革兰阴性（G^-）杆菌占40．1％（122／304）。易感器官依次为呼吸道和胆道,感染发生率分别为81．5％（248／304）,15．1％（46／304）。呼吸道感染以G^＋菌为主,占65．3％,胆道感染以G^-为主,占60．9％,两者有显著性差异（P〈0．01）。结论肝移植术后细菌感染率高,主要以G^＋球菌感染为主,条件致病菌及多重耐药菌株较多见。肝移植术后细菌感染的菌群与部位间有明显相关关系,在预防或治疗感染时应针对不同感染部位采取不同措施。     

肝移植术后早期高胆红素血症的临床研究

目的探讨原位肝移植术后1月内导致高胆红素血症的原因,并提出其防治措施。方法通过对41例原位肝移植患者1月内的临床表现、实验室检查、影像学及移植肝病理学检查等资料回顾性分析,确定肝移植术后早期高胆红素血症的原因,并提出相应的防治措施。结果本组术后早期发生高胆红素血症的主要原因包括：保存（含再灌注损伤）（35例,85．4％）,胆道并发症（18例,43．9％）,急性排斥反应（13例,31．7％）,血管并发症（5例,12．2％）,感染并发症（20例,48．8％）,术前高胆红素血症（12例,29．2％）,药物毒性反应（4例,9．8％）。通过对其原因及时处理,于术后满1月时28例高胆红素血症基本消失,临床治愈率为68．3％（28／41）,6例效果不明显,7例死亡。结论肝移植术后早期高胆红素血症通常是多种原因同时或相继作用所致,其中保存及再灌注损伤、胆道并发症、急性排斥反应以及感染并发症是最常见的原因,早期病因诊断、根据不同的病因作相应的处理是提高其治愈率的关键。     

肝移植术后胆道并发症的介入治疗

目的探讨介入治疗在肝移植术后胆道并发症治疗方面的作用。方法回顾性分析本中心2004年4月至2006年10月采用介入方法治疗的37例肝移植术后胆道并发症患者的I临床资料。结果本中心肝移植术后胆道并发症的发生率为7．2％（30／417）。介入治疗的近期治愈率为54．1％（20／37），近期治愈患者中需反复治疗的比率是40％（8／20），围手术期病死率为5．4％（2／37），总病死率为16．2％（6／37）。吻合口漏、胆道坏死导致的胆漏、吻合口狭窄、非吻合口狭窄、胆泥和胆石形成的介入治疗治愈率分别为57．1％（4／7）、0（0／4）、100％（8／8）、16．7％（2／12）、100％（6／6）。结论介入治疗是肝移植术后胆道并发症的重要治疗方法。疗效与胆道并发症的类型相关，吻合口狭窄、胆泥和胆石形成以及吻合口漏的介入治疗效果良好；胆道坏死导致的胆漏及非吻合口狭窄的介入治疗效果较差，应把握好时机进行再次肝移植。     

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目的 研究肝移植术后细菌感染的流行病学规律。方法 回顾性分析175例病人180次原位肝移植术后细菌学资料。结果 肝移植术后感染率为62．8％（113／180），平均感染时间为术后第9天；共分离出菌株284株，其中革兰阴性（G^-)杆菌占54．6％（155／284）；最常见的G^-杆菌为铜绿假单胞菌，最常见的革兰阳性（G^-)球菌为粪肠球菌。易感器官依次为呼吸道，腹腔和胆道，感染率分别为37．3％（106／284），31．0％（88／284），21．1％（60／284）。结论 肝移植术后细菌感染率高，并以高度耐药菌为主，肝移植术后细菌感染部位与时间及菌群间有明显相关关系。     

肝移植术后缺血型胆道病变的研究进展

肝移植术后的胆道并发症是肝移植的致命弱点，是阻碍肝移植疗效提高的重要因素。因此，它被肝移植先驱Calne爵士称为“阿咯琉斯之踵”（the heel of Achilles）。随着对肝移植胆道并发症的进一步认识和外科技术的提高，因外科技术原因造成的吻合口、引流管相关并发症发生率呈下降趋势，而非外科技术原因的移植肝缺血型胆道病变（ischemic—type biliary lesion，ITBL）则成了肝移植术后胆道并发症的主要类型。因此，被称为“阿咯琉斯之踵再现”。缺血型胆道病变是指肝移植术后移植肝非吻合技术性的胆管树的破坏，其发生率为29／6～19％。由于其发病原因复杂，临床处理困难，已成为影响肝移植患者长期存活及导致移植物丢失的主要原因之一。为此，肝移植术后缺血型胆道病变的研究已引起了全球移植专家的高度重视。     

肝移植术后受者焦虑状况调查及病因探讨

目的调查肝移植术后受者的焦虑状况并探讨其病因。方法研究对象为2006年3月在本中心门诊随访的肝移植受者105名。采用汉密尔顿焦虑量表对研究对象进行问卷调查。结果105例肝移植受者可能有焦虑、肯定有焦虑、肯定有明显焦虑和有严重焦虑的发生率分别为45．7％（48／105）、15．2％（16／105）、7．6％（8／105）和0（0／105）。大学文化程度、高中和中专文化程度、初中及以下文化程度肝移植受者焦虑发生率分别为15．8％（6／38）、27．6％（8／29）和26．3％（10／38），三者间差异无统计学意义（P〉0．05）。60岁及以上、50～59岁、40～49岁和20～39岁肝移植受者焦虑的发生率分别为30％（6／20）、18．8％（6／32）、29．6％（8／27）和15．4％（4／26），四者间差异无统计学意义（P〉0．05）。原发病为慢性乙型肝炎（重型）、乙型肝炎后肝硬化、原发性肝癌合并肝硬化和其他的肝移植受者焦虑发生率分别为19．2％（5／26）、22．9％（8／35）、24．3％（9／37）和28．6％（2／7），四者间差别无显著性（P〉0．05）。术后0～180d、180～365d、366～730d和〉730d的肝移植受者焦虑发生率分别为35．7％（5／14）、17．9％（5／28）、22．2％（12／54）和22．2（2／9）。结论肝移植术后受者有较高的焦虑发生率。肝移植受者的精神心理健康应受到关注，以进一步提高肝移植受者的生存质量。     

肝移植术后缺血性胆管病变的影像学研究进展

<正>原位肝移植(orthotopic liver transplantation,OLT)已成为治疗终末期肝病的有效方法。尽管移植外科的进步和免疫抑制剂的研发使移植受者的生存率有了明显的提高,但OLT术后的胆道并发症一直是受体移植肝功能不良、损伤甚至丢失的主要原因之一。其中,缺血性胆管病变(ischemic-type biliary lesions,ITBL)是肝移植术后较为棘手的胆道并发症之一。ITBL是由于血供破坏而导致的胆管局部或广泛的损害,可伴有胆泥或胆石形成,甚至发生移植肝无功能。ITBL的病变位于非吻合口     

原位肝移植术后再手术的原因分析

目的探讨导致原位肝移植术后再手术的原因。方法回顾性分析4年间所施行225例原位肝移植的临床资料，对其中病例需行再手术的原因进行分析总结。结果225例患者中，有27例患者肝移植后因出血等原因需再次手术，其中5例接受2次再手术，再手术率为14．2％（32／225）。再手术原因包括：腹腔内出血17例次，占再手术总例次的53．1％（17／32）；胆道并发症11例次，占再手术总例次的34．3％（11／32）；肝动脉栓塞2例次，占再手术总例次的6．3％（2／32）；其它2例次，其中上消化道出血1例、胸腔出血1例，占再手术总例次的6．3％（2／32）。再手术方式包括缝扎出血点、渗血创面电凝、胆道吻合口重建、肝动脉重建及再次肝移植等。27例再手术病例中，7例患者再手术后死亡，死亡率为25．9％（7／27）。结论原位肝移植术后再手术的原因是多方面的，其中腹腔内出血及胆道并发症是两大主要原因；认识术后再手术的原因，并采取正确的处理，对降低原位肝移植患者的死亡率具有重要意义。     

The Importance of Portal Venous Blood Flow in Ischemic‐Type Biliary Lesions after Liver Transplantation

Ischemic‐type biliary lesions (ITBL) are the most frequent cause of nonanastomotic biliary strictures after liver transplantation. This complication develops in up to 25% of patients, with a 50% retransplantation rate in affected patients. Traditionally, ischemia‐reperfusion injury to the biliary system is considered to be the major risk factor for ITBL. Several other risk factors for ITBL have been identified, including the use of liver grafts donated after cardiac death, prolonged cold and warm ischemic times and use of University of Wisconsin preservation solution. In recent years however, impaired microcirculation of the peribiliary plexus (PBP) has been implicated as a possible risk factor. It is widely accepted that the PBP is exclusively provided by blood from the hepatic artery, and therefore, the role of the portal venous blood supply has not been considered as a possible cause for the development of ITBL. In this short report, we present three patients with segmental portal vein thrombosis and subsequent development of ITBL in the affected segments in the presence of normal arterial blood flow. This suggests that portal blood flow may have an important contribution to the biliary microcirculation and that a compromised portal venous blood supply can predispose to the development of ITBL.     

人肝移植的抗体介导性排异与ABO配型不同之间的关系

目的探讨人肝移植的抗体介导性排异与ＡＢＯ配型不同之间的关系。方法实验组为３１例ＡＢＯ配型不同（ＡＢＯ－Ｉ）肝移植病例，并设立了ＡＢＯ配型相同（ＡＢＯ－Ｃ）的临床对照组和病理对照组，观察移植肝脏的存活时间、病理学特征和发病原因。结果ＡＢＯ－Ｃ临床对照组移植肝存活时间比ＡＢＯ－Ｉ组明显延长（Ｐ＜０．０１），而且病理所见和发病原因与ＡＢＯ－Ｉ组有明显不同。ＡＢＯ－Ｃ病理对照组与ＡＢＯ－Ｉ组的病理改变和免疫荧光检查均有所不同。结论移植肝脏存在抗体介导性排异的潜在因素和某些临床及病理改变，只是尚未达到普遍认同的诊断标准。     

Increased bile duct complications in liver transplantation across the ABO barrier.

OBJECTIVE: This study evaluated the outcome of liver grafts from ABO incompatible donors, focusing on biliary complications, and compared the results to an ABO compatible control group. Also, the expression of donor ABH antigens in the liver graft was analyzed. SUMMARY BACKGROUND DATA: The outcome of liver transplantation using an ABO incompatible graft is still debated. These blood group related (ABH) antigens are known to be expressed not only on the surface of the erythrocytes, but also on the epithelial cells of large bile ducts. Because the biliary epithelium of hepatic allografts may continue to express donor ABH antigens, it may be more susceptible to immunologic bile duct injury after transplantation across the ABO barrier. METHODS: Eighteen ABO incompatible grafts were compared with 18 ABO compatible grafts in patients who were matched according to medical urgency, primary liver disease (PLD), and recipient age. After transplantation, the grafts were analyzed with cholangiography, Doppler ultrasound, or arteriography and liver histology according to protocol. Immunoperoxidase staining for ABH antigens was performed on hepatic tissue. RESULTS: Biliary complications developed in 82% of the ABO incompatible donors, compared to 6% of the ABO matched controls. Hepatic artery thrombosis occurred in 24%. Cellular rejection was diagnosed in 65% versus only 28% in the control group. The 1-year actuarial graft survival rate was 44% versus 78% in the control group. ABH antigens of the donor were expressed on vascular endothelium and bile duct epithelial cells as long as 150 days after transplant. CONCLUSIONS: Using ABO incompatible allografts, a high incidence of biliary and hepatic artery complications and decreased graft survival in liver transplantation were found. An immunologic injury to the bile duct epithelium and/or to vascular endothelium is suspected.     

Liver transplantation across ABO blood groups

Six hundred seventy-one first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of donor-recipient mismatches or incompatibilities for the ABO blood groups on graft survival. A significant advantage for ABO donor-recipient identity was found, especially in adults and for first grafts. However, a surprisingly large number of ABO incompatible grafts were successful. We recommend that nonidentical or incompatible grafts be limited to patients such as small children for whom the supply of available donors is severely limited or for patients in urgent need of transplantation or retransplantation.     

Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation

We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery. The arterial flow was reestablished and maintained in 5 (38.5%) of the 13. Recurrent thrombosis in the other 8 grafts developed 2 to 24 days (mean, 13.8 days) after transplantation. Reconstruction was successful in 50% (4/8) of the adults, compared with only 20% (1/5) of the children. Satisfactory results were obtained when a definitive cause of thrombosis could be identified. We conclude that early recognition and correction of the cause of hepatic artery thrombosis during or after orthotopic liver transplantation, especially in adults, is often a graft-saving and lifesaving procedure worthy of consideration.     

Survival following liver transplantation from non-heart-beating donors

OBJECTIVE: To determine whether patient and graft survival following transplantation with non-heart-beating donor (NHBD) hepatic allografts is equivalent to heart-beating-donor (HBD) allografts. SUMMARY BACKGROUND DATA: With the growing disparity between the number of patients awaiting liver transplantation and a limited supply of cadaveric organs, there is renewed interest in the use of hepatic allografts from NHBDs. Limited outcome data addressing this issue exist. METHODS: Retrospective evaluation of graft and patient survival among adult recipients of NHBD hepatic allografts compared with recipients of HBD livers between 1993 and 2001 using the United Network of Organ Sharing database. RESULTS: NHBD (N = 144) graft survival was significantly shorter than HBD grafts (N = 26856). One- and 3-year graft survival was 70.2% and 63.3% for NHBD recipients versus 80.4% and 72.1% (P = 0.003 and P = 0.012) for HBD recipients. Recipients of an NHBD graft had a greater incidence of primary nonfunction (11.8 vs. 6.4%, P = 0.008) and retransplantation (13.9% vs. 8.3%, P = 0.04) compared with HBD recipients. Prolonged cold ischemic time and recipient life support were predictors of early graft failure among recipients of NHBD livers. Although differences in patient survival following NHBD versus HBD transplant did not meet statistical significance, a strong trend was evident that likely has relevant clinical implications. CONCLUSIONS: Graft and patient survival is inferior among recipients of NHBD livers. NHBD donors remain an important source of hepatic grafts; however, judicious use is warranted, including minimization of cold ischemia and use in stable recipients.     

Increased risk of antibody-mediated rejection of reduced-size liver allografts

Because of the shortage of liver allografts in children, transplantation of reduced-size liver allografts from adult cadaveric donors or living, related donors is being done more frequently. Reduced-size liver allografts may be used in cases of ABO incompatibility and T-cell warm cross-match positivity. This experimental study in inbred rats was undertaken to determine if reduced-size liver allografts are more sensitive to antibody-mediated rejection than full-size liver allografts. Brown-Norway (BN) (RT1(n)) rats were sensitized by three successive skin grafts at 10-day intervals. Then orthotopic Lewis (LEW) (RT1(1)) liver grafts were transplanted into these BN rats. Full-size liver allografts were compared with reduced-size liver allografts (70% of donor liver). Control groups were composed of full-size and/or reduced-size isografts. Titers of specific antibodies were assayed using a complement-dependent assay before and after orthotopic liver transplantation. Histological and immunofluorescence studies (IgG, IgM, C(3), and fibrinogen deposits) were assessed. Recipients of reduced-size liver allografts died of hyperacute rejection at 36.6 +/- 4.1 h, significantly earlier than recipients receiving full-size liver allografts, which died of accelerated acute rejection at 259.2 +/- 25.2 h (P < 0.001). Either full-size or reduced-size isograft recipients survived indefinitely. A decrease in the titers of donor-specific antibodies was observed in both groups of animals. Slight deposits of IgG, IgM, C(3), and fibrinogen were observed in recipients of reduced-size liver allografts, whereas larger deposits were observed in recipients of full-size liver allografts. Our data demonstrate that there is an increased risk of antibody-mediated rejection of reduced-size liver allografts in sensitized recipients. This may have important clinical implications for partial liver grafting in cases of ABO incompatibility and T-cell warm cross-match positivity.     

Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation

Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft‐loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term ‘splenic artery syndrome’ (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil‐embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty‐six patients were treated with coil‐embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil‐embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post‐transplant coil‐embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.     

Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation – a randomized clinical trial

Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.     

A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver

A new solution which can extend successful preservation times for hepatic allografts was recently developed at the University of Wisconsin (UW). To examine the mechanism of improved viability using this solution, we developed a model of orthotopic hepatic transplantation in the rat. As a baseline study, we compared parameters of viability of allografts preserved in Collins solution to those preserved in UW, including survival, bile output, peak AST, and allograft weight change during storage. Seventy-four rats were transplanted following storage in Collins solution and 70 rats were transplanted after storage in UW. Cold-storage time varied between 2 and 24 hr. The survival with preservation in UW was significantly better than that with Collins when storage time was greater than 2 hr. The preservation time for a viable organ using UW was greater than double that using Collins. The peak AST using UW was lower than that with Collins for cold ischemic times (CIT) up to 10 hr, with significance demonstrated at 5-6 and 7-8 hr when compared with Collins. Prolonged CIT resulted in an increase in liver weight with Collins-preserved livers and a decrease in weight with UW-preserved livers. Using a model of orthotopic liver transplantation in the rat, we demonstrated a doubling of preservation time when UW solution was substituted for Collins. Similar improvements in recipient survival and biochemical parameters of injury have been demonstrated in the canine model and in human clinical trials.