Pulmonary hypertension: considerations in the liver transplant candidate

Pulmonary hypertension is a potentially lethal complication of end-stage liver disease with a prevalence of 2%. In the setting of liver transplantation, the prevalence may be as high as 12%. Given the potential importance of this syndrome to the transplantation community, the purpose of this review is to summarize the current state of understanding of portopulmonary hypertension and to suggest potential management strategies for (1) liver transplant candidates with suspected pulmonary hypertension and (2) intraoperative pulmonary hypertension following liver allograft reperfusion.     

Extrahepatic biliary stricture associated with cytomegalovirus in a liver transplant recipient

We describe a patient who developed a stricture in the distal common bile duct 6 weeks after orthotopic liver transplantation. Histopathologic examination of the bile duct epithelium in the region of the stricture showed characteristic cytomegalovirus (CMV) inclusions. CMV was also identified in pulmonary alveoli and in the duodenum. Although CMV has been demonstrated in the biliary epithelium of AIDS patients with extrahepatic biliary strictures and biliary obstruction, this entity has not, to our knowledge, been described in liver transplant recipients. This report confirms that CMV infection should be included as a probable cause of extrahepatic biliary strictures and bile duct obstruction in liver transplant patients.     

Dysarthria and cerebellar ataxia: late occurrence of severe neurotoxicity in a liver transplant recipient

Neurological complications of cyclosporin (CyA) therapy are frequent, usually occurring within the 1st month after transplantation. Though leukoencephalopathy is one of them, it is rarely documented. Here we report the case of an anti-HCV-positive patient with cirrhosis who underwent liver transplantation and developed cyclosporin-induced leukoencephalopathy. The presenting symptoms were dysarthria, difficulty walking, and dysphagia. They were first noted 6 months after transplantation in association with an episode of recurrent HCV acute hepatitis. White matter abnormalities were evident on computed tomography (CT) scanning and magnetic resonance (MR) imaging. This condition improved to some degree after cyclosporin withdrawal. To our knowledge this is the second reported case of CyA neurotoxicity occurring late after liver transplantation. Moreover, the association with acute hepatitis suggests the possibility of graft dysfunction as a contributing and triggering factor.     

Split liver is an effective tool to transplant paediatric patients

Abstract Transplantation activity is dependent upon organ procurement; although great efforts are made to enlarge the cadaver donors' pool, it still remains far too small to meet the recipients' need. Waiting time is a particular problem for paediatric patients, and mortality on the waiting list for liver transplantation is very high. The number of paediatric donors is far too small to satisfy the request. To enlarge the liver pool, the split‐liver procedure was introduced in several Transplant Centers. In November 1997, the North Italy Transplant program (NITp) Working Group for Liver Transplantation decided to start an official Split‐liver Program. A protocol was therefore defined and criteria for donor's and recipient's eligibility were established to minimize the risk. The Working Group also standardized the technical procedure and defined collaboration between centers. Out of 410 cadaver liver donors used in the NITp, from 1 November 1997 until 31 May 1999, 49 patients (37 males and 12 females) were chosen for the split‐liver procedure. Mean age was 29.9 ± 17.5 years. Mean ICU stay of the donors was considerably short (2.5 ± 2.1 days), and the other conditions foreseen for donor eligibility were met. In all cases (except two) an “in situ” technique was performed. Forty‐nine adult recipients and 43 children were transplanted by the split‐liver technique in our Transplant Centers. One right lobe and five left liver lobes were sent to Transplant Centers outside the NITp. Adult recipient age ranged from 18 to 60 years (mean 46.4 ±11.7 years), and the paediatric one from 2 to 144 months (mean 24.8). Mean patient follow‐up was 8.3 ± 5.5 months. In the paediatric group, the graft was successful in 34 cases (79 %), five patients (10.2 %) died and four (9.3 %) were re‐transplanted. In the adult group, graft survival was 67.3 %, 11 (22 %) patients died and 5 (10 %) were re‐transplanted. On 1 November 1997, 30 paediatric patients were on the liver waiting list. In the preceding 19 months, 52 patients were newly enrolled, and 36 transplants were performed. The mean waiting time of paediatric patients was 259 days (range 1‐919 says). From 1 November 1997 to 31 May 1999, 61 paediatric patients were newly enrolled. In this period 70 patients were transplanted. The mean waiting time was 185 days (1‐1010 days). At present, the liver waiting list includes eight paediatric patients. Split‐liver transplantation is a successful procedure, effective in reducing waiting time for paediatric patients. It should be established if this may be a tool to enlarge the organ pool also for adult liver transplantation.     

Hepatic artery interruption followed by portal vein thrombosis in an adult liver transplant

Vascular complications following liver transplantation result in significant morbidity and mortality. We report a 28-year-old man who, because of a mycotic false aneurysm, underwent ligation of the hepatic artery 4.5 weeks post-transplantation and who, 4.5 months later, suffered a portal-mesenteric vein thrombosis. Adverse hepatic sequelae did not follow these events, demonstrating the capacity of the collateral circulation to perfuse the transplanted liver.     

Herpes zoster-associated idiopathic thrombocytopenic purpura in a liver transplant recipient: a case report and overview

Idiopathic (autoimmune) thrombocytopenic purpura has been previously reported as a rare complication in children and in a few adults following chickenpox. We report a case of varicella zoster virus-associated idiopathic thrombocytopenic purpura in an adult liver transplant recipient following dermatomal zoster. Idiopathic thrombocytopenic purpura developed 3 days after the onset of herpes zoster in our patient, with a nadir platelet count of 3000/mm³. The patient was treated with intravenous gamma globulin with recovery of thrombocytopenia after 3 weeks. Transplant clinicians need to be aware that this serious and potentially life-threatening complication may occur with herpes zoster in transplant recipients.     

Plasma proteolytic activity in liver transplant rejection

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and α₂-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F 1 + 2), and plasmin/α₂-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Received: 20 January 1998 Received after revision: 11 September 1998 Accepted: 12 October 1998     

Preservation of renal perfusion and postoperative renal function by side-to-side cavo-caval anastomosis in liver transplant recipients

Postoperative renal failure is common after liver transplantation (LT). The aim of this study was to investigate peroperative renal perfusion and postoperative renal function in 12 patients who underwent LT with side-to-side cavocaval anastomosis (SSCCA). Three phases were considered during the procedure: hepatectomy, the anhepatic phase, and the postreperfusion phase (phases 1, 2, and 3, respectively). Mean arterial pressure, IVC pressure, and renal perfusion pressure were significantly higher during phase 2 than during phases 1 and 3. Cardiac index and pulmonary capillary wedge pressure did not differ significantly during the three phases. Creatinine clearance did not significantly decrease postoperatively. We conclude that SSCCA is associated with both the preservation of renal perfusion pressure during the entire procedure and the preservation of postoperative creatinine clearance. It is, moreover, a technique that results in a low rate of postoperative renal failure after LT.     

Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P<0.05). Concurrently, an increase in CVP (P<0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.     

肝移植术后胆道并发症的诊断与治疗

目的 探讨肝移植术后胆道并发症的诊断与治疗.方法 分析2007-2009年肝移植术后不同类型胆道并发症的患者的临床资料,评价胴道并发症的类型,处理方式及术后恢复情况.结果 肝移植术后胆道并发症患者23例,包括胆漏患者12例,计胆管吻合口漏7例,肝断面胆管漏3例,胆囊管漏1例,迷走胆管漏1例;移植术后胆管狭窄患者11例,其中吻合口狭窄4例,非吻合口性狭窄7例.7例吻合口漏患者中,胆管重建2例(Roux-en-Y吻合和胆肠襻式Warren吻合);胆道吻合口修补1例;单纯依靠外引流管引流1例,活体双供肝肝移植的患者剖腹探查纠正胆漏失败后行再次肝移植1例;行经内镜逆行胰胆管造影(endoscopic retrograde cholangiopancreatography,ERCP)植入支架2例.肝断面胆管漏3例中,行肝断面胆管缝扎1例,ERCP联合B超引导下穿刺引流2例,引流2个月后胆漏闭合,拔除引流管,但是随后又出现胆道狭窄,ERCP术后,病情好转.胆囊管漏1例,行胆囊管缝扎.迷走胆管漏1例,行胆囊床缝扎.吻合口狭窄的患者4例,3例经ERCP治愈,1例行胆肠吻合重建胆道后治愈.非吻合口性狭窄的7例,行ERCP治疗3例,ERCP失败后,行经皮肝穿刺胆管引流(percutaneous transhepatic cholangiographic drainage,PTCD)1例;再次肝移植3例,2例患者术后恢复良好,1例死于严重感染.结论 肝移植术后胆道并发症危害大,关键在于预防.     

Pediatric liver transplantation from neonatal donors

Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors.     

Relevance of a positive crossmatch in liver transplantation

We studied 27 liver transplants in 24 patients performed between November 1984 and January 1988. We investigated retrospectively the importance of donor reactive HLA class I and class II and of non-HLA antibodies for graft survival in these patients. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A,-B,-C and DR and DQ antigens to block cytotoxicity of sera and the reagent dithiothreitol to characterize the immunoglobulin class. We found that humoral immunity to HLA antigens in liver-grafted patients, demonstrable as the presence of cytotoxic antibodies reactive with donor splenic T and/or B cells in the pretransplantation period, is associated with significantly lower graft survival as compared with patients without demonstrable preformed HLA antibodies (P=0.01). In addition we found that a substantial proportion of patients had donor-reactive cytotoxic antibodies which were not HLA specific. Thus, our study shows that HLA immunity can influence liver allograft survival, and that it is useful to have patient cytotoxic antibodies characterized with regard to HLA reactivity prior to transplantation.     

The intra-operative use of trasylol (aprotinin) in liver transplantation

Aprotinin has been reported to reduce blood loss in difficult cases requiring cardiopulmonary bypass surgery and more recently in liver transplantation. Over a 9-month period were compared the effects of an intra-operative infusion of aprotinin on transfusion requirements and coagulation profiles in 12 patients undergoing liver transplantation for end-stage cirrhosis with an equal number of consecutive transplants in patients with similar pathology who did not receive aprotinin. Transfusion of blood and blood products was reduced to one-third in the aprotinin-treated group. Operative time was also significantly reduced, as was ICU stay post-operatively. Aprotinin profoundly inhibits fibrinolysis and this is likely to be the major effect by which blood loss is reduced. Thromboelastography revealed severe fibrinolytic changes in the anhepatic stage in 4 of 6 controlled patients; this accelerated in 3 following reperfusion of the new graft. By contrast, only 1 patient of 12 in the aprotinin-treated group showed fibrinolytic activity in the anhepatic period, and none showed evidence of fibrinolysis following reperfusion of the new graft.     

肝癌患者术前HBV DNA定量水平与肝移植术后肝癌复发关系的探讨

目的 探讨肝癌肝移植患者术前乙型肝炎病毒(hepatitis B virus,HBV)DNA定量与肝移植术后原发性肝细胞癌(hepatocellular carcinoma,HCC)复发的关系.方法 回顾性分析2004年1月到2008年12月因同时合并HCC和HBV行肝移植手术并长期随访的148例患者,使用Kaplan-Meier生存分析统计患者生存率和无瘤生存率,根掘术后HCC是否复发将患者分成HCC复发组(43例)及未复发组(105例),使用COX多因素回归进行危险因素分析.结果 148例HCC肝移植患者1、3、5年生存率分别为86%,72%,72%,无瘤生存率分别为79%,71%,54%.肝移植术后HCC复发43例,复发率为29.1%(43/148),术后HCC平均复发时间为(13.16±14.17)个月(1～54个月).COX多因素回归分析表明超过米兰标准(HR=9.89;95%CI2.30～42.52;P=0.002)以及术前HBV DNA＞5log10 copies/ml(HR=2.26;95%CI1.01～5.04;P=0.047)是肝移植术后HCC复发的独立危险因素.结论 肝移植术前HBV DNA＞5log10 copies/ml和超过米兰标准是原发性肝癌患者肝移植术后HCC复发的高危因素.     

Combined liver and kidney transplantation

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.     

Results after liver retransplantation in a group of 50 regrafted patients: two different concepts of elective versus emergency retransplantation

Liver retransplantation remains the only alternative therapy for irreversible graft failure. Previous studies have demonstrated lower survival rates for liver retransplantation than for primary grafts. After reviewing our clinical experience with 55 retransplantations out of 365 liver transplants, we found that the risk and results depend on the surrounding circumstances. Elective retransplantation was shown to be as safe as the first liver transplantation, while emergency retransplantation yielded significantly higher morbidity and mortality rates.     

Post-transplant lymphoma in a liver allograft

We describe the development of a lymphoma in a liver allograft shortly after orthotopic liver transplantation. Aspiration and core biopsies of the nodule were persistently negative so that a diagnosis could not be made until the patient underwent retransplantation, when examination of the liver resection specimen revealed a B-cell lymphoma. Using a rapid technique based on the polymerase chain reaction, we were able to demonstrate that the tumor was of donor origin.     

Transjugular intrahepatic portosystemic shunt and liver transplantation

Transjugular intrahepatic portosystemic stent shunting (TIPSS) appears to be an attractive, nonsurgical procedure to overcome complications of end-stage liver disease. During the period August 1992 to February 1995, 23 adults who had previously undergone TIPSS received liver transplants. These patients were compared to 36 cirrhotic patients, grafted during the same time period, in relation to the implantation technique, the intraoperative use of blood products, and the length of their hospital stay. These groups were comparable for previous right upper quadrant surgery, splanchnic vein modifications, and Child-Pugh classification. Liver transplantation was performed electively in all TIPSS patients. Ten patients (43.4%) presented with a significant shunt stenosis at a median follow-up time of 4.5 months (range 2.5 to 30 months). At transplantation 8 of the 23 TIPSS patients (34.8%) had specific TIPSS-related modifications i.e., extrahepatic portal vein aneurysm formation (n=2), dislocation of the distal end of the stent into the inferior vena cava (n=4) or into the main portal vein trunk (n=1), bilioportal fistula (n=1), and pronounced phlebitis of the inferior vena cava and hepatic veins due to redilation of shunt stenosis (n=4). The intraoperative blood product requirement at transplantation was similar in the 23 TIPSS-patients and in the 36 cirrhotic patients who received transplants without the TIPSS procedure during the same time period [median 800 ml (range 0–20300 ml) vs median 620 ml (range 0–7600 ml), respectively]. There was also no difference between the two groups in length of hospital stay [median 18 days (range 0–34 days) vs median 19 days (range 0–66 days), respectively]. We conclude that TIPSS plays an important role in the management of life-threatening complications of end-stage liver disease arising in potential liver transplant candidates. TIPSS should be considered as a temporary, effective bridge to elective transplantation and not as a means to lower the blood product requirement at transplantation. Specific TIPSS-related modifications should be recognized early by the transplant surgeon in order to adapt the technique of graft implantation.     

Loss of speech after orthotopic liver transplantation

Alteration of speech is a rare but distressing complication of orthotopic liver transplantation (OLT). We describe a characteristic speech disorder identified in a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525 adults underwent OLT. For all recipients with neurologic complications, we reviewed clinical findings, imaging and electrophysiologic test results, and perioperative laboratory data. Five patients (ages 23–52; UNOS status 3–4) exhibited a characteristic pattern of stuttering dysarthria, leading to complete loss of speech production, occasionally with elements of aphasia. In four of the five patients, right-sided focal seizures were subsequently noted. All cases presented within the first 10 postoperative days and improved within 1 month of cessation of cyclosporin (CyA), although halting, monotonous speech was evident to some degree in all five for up to 1 year. There was no correlation between onset of symptoms and CyA levels. None of the patients had clinical or radiologic findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and Spect scan results were consistent with dysfunction in the left frontotemporoparietal regions of the brain. A characteristic speech disorder, which may be described as cortical dysarthria or speech apraxia, occurs in approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome and temporary cessation of CyA therapy may favorably affect the course.     

Reduced size liver transplantation,split liver transplantation,and living related liver transplantation in relation to the donor organ shortage

Because of the shortage of cadaveric donors, three techniques of partial liver grarting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now.