Liver retransplantation in adults: a single-centre, 25-year experience

Background:

Retransplantation is the only form of treatment for patients with irreversible graft failure. The aim of this study was to analyse a single centre''s experience of the indications for and outcomes of retransplantation.

Methods:

A total of 196 patients who underwent liver retransplantation using 225 grafts, between January 1982 and July 2007, were included in the study. The following parameters were analysed: patient demographics; primary diagnosis; distribution of retransplantation over different time periods; indications for retransplantation; time interval to retransplantation, and overall patient and graft survival.

Results:

Of the 2437 primary orthotopic liver transplantations, 196 patients (8%) required a first regraft, 23 patients (1%) a second regraft and six patients (0.25%) a third regraft. Autoimmune hepatitis was the most common primary diagnosis for which retransplantation was required (12.7% of primary transplantations). The retransplantation rate declined from 12% at the beginning of our programme to 7.6% at the end of the study period. The most common indication for retransplantation was hepatic artery thrombosis (31.6%). Nearly two-thirds of the retransplantations were performed within 6 months of the primary transplantation. The 1-, 3-, 5- and 10-year patient survival rates following first retransplantation were 66%, 61%, 57% and 47%, respectively. Five-year survival after second retransplantation was 40%. None of the patients have yet survived 3 years after a third regraft. Donor age of ≤55 years and a MELD (Model for End-stage Liver Disease) score of ≤23 were associated with better outcome following retransplantation.

Conclusions:

First retransplantation was associated with good longterm survival. There was no survival benefit following second and third retransplantations. A MELD score of ≤23 and donor age of ≤55 years correlated with better outcome following retransplantation.     

Liver retransplantation:report of 80 cases and review of literature

BACKGROUND: Because the orthotopic liver transplantation (OLT) was performed widely in recent 5 years throughout China, the proportion of recipients whose graft function deteriorated to be retransplantation candidates increased gradually. This study was undertaken to analyze clinical experience of orthotopic liver retransplantation (re-OLT) at our center. METHODS: The medical records of 80 patients who had undergone liver retransplantation at our center from January 1999 to July 2005 were analyzed retrospectively, including indications and timing of retransplantation, surgical techniques, and the causes of death. RESULTS: The commonest cause leading to hepatic graft loss and subsequent retransplantation was biliary complications in 36 patients (45%). The patients underwent retransplantation more than 30 days after their primary transplant recovered better than those who underwent retransplantation within 8-30 days after primary transplantation (peri-operative mortality 19.6% versus 70%). Sepsis (12 of 22 patients, 54.5%) and multiple organ failure (4 of 22 patients, 18.2%) were leading causes of re-OLT recipient deaths. CONCLUSIONS: Proper indications and optimal operative time, surgical procedures, perioperative monitoring and appropriate postoperative treatment contribute to the improvement of the survival rate of patients after liver retransplantation.     

Report of 8 cases of liver retransplantation

BACKGROUND: Retransplantation of the liver is required for several complications of primary grafting, such as primary allograft non-function, hepatic artery thrombosis, biliary problems, or chronic ductopenic rejection. Surgeons usually take regrafting as the only pathway to treat those patients who are considered to have a poor outcome after the first operation. Whether the retransplantation is early or late, further attempts at rescue with a second or more grafts are associated with higher mortality and morbidity. However, retransplantation plays a role in improving survival of the patients. Therefore, it is necessary to summarize the experiences in liver retransplantation, as well as the factors influencing operative effects. METHOD: The clinical data of 8 patients who received liver retransplantation in our center were analyzed retrospectively. RESULTS: Complications of the biliary tract occurred in 5 of the 8 patients, chronic rejection in 2, and embolism in the hepatic artery in 1. Infections occurred in 7 patients before engraftment. Patient 1 had developed renal failure before the surgery, and he died of severe infection and multi-organ failure after transplantation. Patient 4 had a massive hemorrhage during the operation and also died of multi-organ failure after transplantation. Patient 7 developed intracranial hemorrhage and abdominal infection and died soon after transplantation. The other 5 patients recovered and discharged from the hospital. CONCLUSIONS: Liver retransplantation is the only measure that can be taken to save the lives of patients whose liver allograft fails to function. It is very important that the indications and time of retransplantation are carefully selected. Factors leading to harmful effects on retransplantation include the preoperative condition of the recipient, a difficult and prolonged operation, massive hemorrhage during the operation, and severe complications after the surgery.     

Adult hepatic retransplantation. UCL experience.

INTRODUCTION: Retransplantation is a rescue operation in orthotopic liver transplantation. Its appropriateness has been questioned on medical, economical and also on ethical grounds. MATERIAL AND METHODS: During the period february 1984-december 1997, 54 (14.5%) of 372 adult patients were retransplanted; three (0.8%) of them had two retransplantations. Indications were graft dysfunction [(primary non function (8x) and early dysfunction (14x in 13 patients)], immunological failure [acute (9x in 8 patients) and chronic (9x) rejection], technical failure [(hepatic artery thrombosis (5x in four patients), allograft decapsulation (1x), ischaemic biliary tract lesions (6x)] and recurrent viral allograft disease [HBV (4x) and HCV (1x)]. RESULTS: Five year actuarial patient survival after retransplantation was 70.8%, which was identical to this of non retransplanted patients (72%). Early (< 3 mo) mortality was significantly lower in elective procedures (9.1%--2/22 pat. vs 34.4%--11/32 pat. in urgent procedures--p < 0.05). Mortality was highest in the graft dysfunction (23.8%, 5/21 pat.) and immunological failure (41%, 7/17 pat.) groups. Five of six patients retransplanted for rejection, whilst being on renal support, and two of three patients retransplanted urgently twice died of infectious complications. All patients retransplanted because of recurrent allograft disease were long-term (> 3 mo) survivors. Both HBV-infected patients died of allograft reinfection 7 months later; the two HBV-Delta infected patients were, free of infection, 44 and 6 months after retransplantation under HBV-immunoprophylaxis. Length of hospitalisation after primary transplantation and retransplantation were identical (median of 16 days--range 11 to 40 vs 14 days (range 7 to 110). Economical study during the period 1990-1995 showed that costs of the first hospitalization of primary transplantation and of retransplantation could be equalized during the period 1994-1995 as a consequence of the more frequent use of elective retransplantation (median 1.3 million BF, range 720,988 to 8,887,145 vs 1.1 million BF, range 943,685 to 1,940,409). CONCLUSIONS: Hepatic retransplantation is a successful safety net for many liver transplant patients. Every effort should be made to do this intervention electively under minimal immunosuppression. In case of immunological graft failure and hepatic artery thrombosis retransplantation must be done early in order to avoid infectious complications; the same holds for ischaemic biliary tract lesions which cannot be cured by interventional radiology. Retransplantation for recurrent benign disease should be restricted to those diseases which can be effectively treated by (neo- and) adjuvant antiviral therapy.     

Initial experience with heart and lung transplantation

Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively.     

Hepatic retransplantation in cholestatic liver disease: impact of the interval to retransplantation on survival and resource utilization.

The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P <.01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P <.01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates.     

Normotest and abnormal prothrombin in liver transplantation

Abstract: Postoperative changes in coagulation parameters, including the abnormal plasma prothrombin level, were studied in 95 patients who underwent liver transplantation, and the results were compared with the clinical outcome. The patients were classified into four groups: Group I had a satisfactory postoperative course, (n=76), Group II suffered graft failure or death at 31 days or more after transplantation (n=9); Group III suffered graft failure or death from 8 to 30 days after transplantation (n=4); and Group IV suffered graft failure or death within 7 days of transplantation (n=6). The Normotest, which closely reflected liver graft function, showed an increase immediately after transplantation in Group I, II, and III, but showed a marked decrease in Group IV. In patients with severe acute cellular rejection, the plasma level of abnormal prothrombin (desgamma-carboxy prothrombin) was compared with the histology of the liver biopsy specimen. When liver graft function was good after orthotopic transplantation, the Normotest value recovered to the normal range of 70% or more. Subsequently, graft function remained good when the desgamma-carboxy prothrombin level stayed low, whereas acute cellular rejection was indicated by an elevation of des-gamma-carboxy prothrombin. When the Normotest value was lower than 20% for the first 2 days after transplantation, graft failure was likely. Because des-gamma-carboxy prothrombin was not produced by graft with early failure, the des-gamma-carboxy prothrombin level also remained low. Thus, the Normotest value and the des-gamma-carboxy prothrombin level were both useful parameters for assessing hepatic function and rejection after transplantation.     

Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation

Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure. (Hepatology 1996 May;23(5):971-6)     

The acute vanishing bile duct syndrome (acute irreversible rejection) after orthotopic liver transplantation

The acute vanishing bile duct syndrome can be defined as an irreversible, rejection-related condition that affects hepatic allografts within 100 days after orthotopic liver transplantation and whose presence requires retransplantation. We have observed the acute vanishing bile duct syndrome in 5 of 48 consecutive patients (approximately 10%) who underwent orthotopic liver transplantation. In 4 cases, the condition progressed relentlessly within approximately 7 to 11 weeks after orthotopic liver transplantation from mild rejection to severe rejection to acute vanishing bile duct syndrome. A fifth patient had severe rejection in the first week and required retransplantation after 17 days because of thrombotic venoocclusive disease complicating the acute vanishing bile duct syndrome. Clinically, signs of impending acute vanishing bile duct syndrome included abrupt onset of fever and jaundice and marked elevation of serum bilirubin and alkaline phosphatase levels which persisted despite antirejection treatment. Biopsy specimens revealed destructive cholangitis (rejection cholangitis), ductopenia, and, if retransplantation was delayed, presence of noninflammatory, "burnt-out" portal tracts without bile ducts. We recommend to base the diagnosis of acute vanishing bile duct syndrome on documentation of severe ductopenia in at least 20 portal tracts which may require several consecutive needle biopsies. Rejection arteriopathy which was found in 3 of our 5 cases might have been another important diagnostic clue but could not be recognized prior to retransplantation. The pathogenesis of acute vanishing bile duct syndrome is not clear; until the condition had manifested itself, we found no qualitative differences between acute reversible and irreversible rejection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of survival after liver retransplantation for late graft failure based on preoperative prognostic scores

The current policy for determining priority for organ allocation is based on the model for end stage liver disease (MELD). We hypothesize that severity of graft dysfunction assessed by either the MELD score or the Child-Turcotte-Pugh (CTP) score correlates with mortality after liver retransplantation (re-OLT). To test this hypothesis, we analyzed the outcome of 40 consecutive patients who received re-OLT more than 90 days after primary orthotopic liver transplantation (OLT). The Kaplan-Meier 1-year and 5-year survival rates after re-OLT were 69% and 62%, respectively. The area under the curve (AUC) values generated by the receiver operating characteristics (ROC) curves were 0.82 (CI 0.70-0.94) and 0.68 (CI 0.49-0.86), respectively (P =.11), for the CTP and MELD models in predicting 1-year mortality after re-OLT. The 1-year and 5-year survival rates for patients with CTP scores less than 10 were 100% versus 50% and 40%, respectively, for CTP scores of at least 10 (P =.0006). Patients with MELD scores less than or equal to 25 had 1-year and 5-year survival rates of 89% and 79%, respectively, versus 53% and 47%, respectively, for MELD scores greater than 25 (P =.038). Other mortality predictors include hepatic encephalopathy, intensive care unit (ICU) stay, recurrent hepatitis C virus (HCV) infection, and creatinine level of 2 mg/dL or higher. Analysis of an independent cohort of 49 patients showed a trend for a correlation between CTP and MELD scores with 1-year mortality, with AUC of 0.59 and 0.57, in respective ROC curves. In conclusion, our results suggest that severity of graft failure based on CTP and MELD scores may be associated with worse outcome after re-OLT and provide a cautionary note for the "sickest first" policy of organ allocation.     

Selection criteria and decisions in 375 patients with liver disease,considered for liver transplantation during 1977–1985

ABSTRACT— We performed a prospective study on 375 patients with liver disease, 60% female, for whom orthotopic liver transplantation (OLT) was considered during 1977–1985. Fifty-four per cent had cirrhosis, 8.5% congenital/hereditary disorders, 25% malignant tumour, 6% benign tumour, 2% Budd-Chiari syndrome, 1.5% acute hepatic failure, 3% other diagnoses, and 10% were under 15 years of age. As of July Ist, 1985, 99 patients (47 chronic active/inactive cirrhosis (CAC/CIC), 28 primary biliary cirrhosis (PBC), five hepatocellular carcinoma (HCC), 19 other diagnoses) were accepted for OLT (median age 40 years, 10% under age 15). By that date, 45 patients (median age 42), had had an OLT (20 CAC/CIC, 15 PBC, three biliary atresia, two HCC, five other diagnoses). Fifty-four per cent (201 patients) were rejected for transplantation. The primary reasons for rejection were: no indication (11%), age (5%), other surgical procedures possible (3%), severe liver failure (14%), extrahepatic spread of liver tumour (11%), cardiovascular or pulmonary problems (2%), severe hepatic bone disease (1%), and miscellaneous (7%). Thirty per cent of the patients with CAC/CIC, 38% with PBC, 88% with HCC and 71% with biliary atresia were rejected. In the CAC/CIC, PBC and biliary atresia patients severe liver failure was the most frequent reason for rejection (62%, 50% and 60%, respectively). In HCC, extrahepatic tumour spread was the most frequent reason (72%) for rejection. In this category only two patients (7%) ultimately underwent liver transplantation.     

Rejection rates in a randomised trial of tacrolimus monotherapy versus triple therapy in liver transplant recipients with hepatitis C virus cirrhosis

BACKGROUND: Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus (HCV) infection after liver transplantation. PATIENTS/METHODS: HCV-infected cirrhotic patients randomised to tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1 mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3 months. RESULTS: Twenty-seven patients (MT) and 29 (TT)--median follow up 661 days (range, 1-1603). Rejection episodes (protocol/further biopsies) within first 3 months and use of empirical treatment were evaluated. New rejection was diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with 19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46 (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%), with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal dysfunction, retransplantation, and death were not significantly different. CONCLUSION: Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected liver transplant recipients.     

Apheresis Therapy for Living‐Donor Liver Transplantation

Abstract: Liver transplantation is a fundamental treatment for patients with end‐stage hepatic failure. In order to perform living‐donor liver transplantations under safer conditions, apheresis plays a major role in Japan due to the prevalence of living‐donor liver transplantation wherein later retransplantation is difficult. In our department, the roles of apheresis in liver transplantation are as follows: as bridge therapy to liver transplantation (n = 45); as a supplement to the graft liver until the recovery of hepatic function (n = 77); as treatment for multiple organ failure including posttransplantation renal failure (n = 15); and as a means with which to reduce antibody titers for antibodies such as anti‐A or anti‐B in persons with ABO blood type = incompatible liver transplantation (n = 23). In our department, we have performed 822 liver transplantations at present. Of those cases, 183 were selected wherein apheresis was performed around the time of the operation. In all cases, transplantation with sufficient apheresis was performed before the surgical operation, however, 22 patients (48.9%) died after undergoing surgery. Among the patients who underwent the postoperative apheresis, those in the nonsurvivor group had lower grafted liver weights compared to those of the survivor group. The kidney was the organ that most frequently failed due to postoperative complications. In cases of ABO blood type‐incompatible liver transplantations, patients with high preoperative anti‐A/B IgM antibody titers sustained bile duct complications, patients with high preoperative anti‐IgG antibody titers sustained hepatic necrosis, and patients with high postoperative anti‐A/B IgM and anti‐IgG antibody titers sustained hepatic necrosis most frequently.     

Short-term postliver transplant survival after the introduction of MELD scores for organ allocation in the United States.

BACKGROUND: It has been suggested that the introduction of model for end-stage liver disease (MELD) for organ allocation may reduce overall graft and patient survival since elevated serum creatinine is an important predictor of poor outcome after liver transplantation. OBJECTIVE: In this study, we determined the outcomes of liver transplantation before (PreMELD group, 1998-February, 2002) and after (MELD group, March-December, 2002, n = 4642) the introduction of MELD score, and examined the impact of MELD scores on the outcome in the United States (US). PATIENTS & METHODS: After excluding patients for a variety of reasons (children, live-donor, fulminant liver failure, patients with hepatoma and others who received extra MELD points, multiple organ transplantation, re-transplantation, incomplete data), there were 3227 patients in the MELD group. These patients were compared with 14,593 patients in the preMELD group after applying similar exclusion criteria. The survival was compared using Kaplan-Meier survival analysis and Cox regression survival analysis. RESULTS: There was no difference in short-term (up to 10 months) graft and patient survival between MELD and preMELD groups. However, graft and patient survival was lower in patients with MELD score > or = 30 when compared with those with MELD score <30 after adjusting for the confounding variables. CONCLUSION: Introduction of MELD score for organ prioritization has not reduced the short-term survival of patients, but patients with MELD score of 30 or higher had a relatively poor outcome.     

Adult living donor versus deceased donor liver transplantation: A 10-year prospective single center experience

It has been 4 years since the first, long-term (> 3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) was reported.¹ In this follow up, prospective, IRB approved, 10-year comparison of A2ALLTx to ADDLTx we expand on our initial observations. This data includes: age, gender, ethnicity, primary liver disease, waiting time, pretrans-plant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications.In 10 years, 465 ADDLTx (81.37) and 107 A2ALLTx (18.7%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (54.5% vs. 48.2%). Data regarding overall patient and graft survival and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (9.6% vs. 21.7%) and more biliary complications (27.1% vs. 17.6%).In conclusion, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.     

Occurrence of cirrhosis-related complications is a time-dependent prognostic predictor independent of baseline model for end-stage liver disease score.

BACKGROUND: The model for end-stage liver disease (MELD) is used to prioritize cirrhotic patients awaiting liver transplantation. Many cirrhosis-related complications are indications for transplantation but are not included in MELD. This study investigated the impact of these complications on survival and association with MELD. METHODS: The mortality risk of cirrhosis-related complications, including bleeding esophageal varices, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome and hepatic decompensation, was analyzed using a time-dependent Cox regression model in 227 cirrhotic patients. RESULTS: A total of 281 episodes of complications occurred in 142 (63%) patients. Patients who died had a significantly higher baseline MELD score compared with those who survived (14.5 +/- 4.5 vs 12.8 +/- 3.9, P = 0.004). There was no significant difference in the MELD score between patients with and without the occurrence of complications (13.6 +/- 4.3 vs 12.9 +/- 4.0, P = 0.093). Patients with a higher baseline MELD score tended to develop early complications (rho = -0.598, P< 0.001). Using the Cox regression model, the risk ratio of mortality was 4.9 (95% confidence interval: 3.9-6.3, P< 0.0001) for each additional episode of complication. CONCLUSIONS: The mortality risk increases as the number of complication episodes increases. While patients with repeated complications have a poor outcome, they do not necessarily have a higher baseline MELD score and could be down-staged in the MELD era.     

Long-term survival after cardiac retransplantation: a single-center experience

Cardiac retransplantation is controversial therapy because of a chronic shortage of donor hearts. We retrospectively reviewed short- and long-term outcomes after cardiac retransplantation. Between February 1989 and December 2004, 28 cases of cardiac retransplantation were performed. Indications for retransplantation were primary graft failure (PGF) in 11 patients (39.3%), intractable acute cardiac rejection (IACR) in 4 (14.3%), and coronary allograft vasculopathy (CAV) in 13 (46.4%). The patients had been supported with prolonged cardiopulmonary bypass (CPB) (n = 3), IABP (n = 1), intravenous inotropic support (n = 7), ECMO (n = 3), and VAD (n = 4). Ten patients had no inotropic support. Eight patients died within 30 days postoperatively. The causes of early death were acute rejection (n = 3 ; 37%), MOF (n = 3 ; 37%), PGF (n = 1 ; 13%), and right ventricular failure (n = 1 ; 13%). The causes of late death in 8 other patients were acute rejection (n = 4 ; 50%), CAV (n = 2 ; 25%), MOF (n = 1 ; 13%), and infection (n = 1 ; 13%). The 1-, 5-, 10-, and 15-year survivals were 78.5, 68.4, 54.5, and 38.3%, respectively, for primary cardiac transplantation, and 46.4, 40.6, 32.5, and 32.5% for cardiac retransplantation (P = 0.003). Acute cardiac rejection was the most common cause of death (43.8%). Thirty-day and 1-year survivals of IACR, PGF, and CAV were 50.0/0, 63.6/45.5, and 84.6/68.4%, respectively. Long-term survival after retransplantation was acceptable for patients with CAV and PGF, however, we should select patients carefully if the indication for retransplantation is IACR because of the poor outcome.     

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.     

Complications in 52 liver transplantations excluding graft rejection

We analyzed the postoperative complications excluding graft rejection in 52 consecutive orthotopic liver transplantations performed from March 1986 to November 1988 in 48 patients. Thirteen patients died: one intraoperatively, seven during the first 2 months, and five between 5 and 28 months. Complications were predominant during the first 3 months; infection was the most common complication. The main cause was viral agents. Cytomegalovirus was responsible for infection in 62 percent of cases, but was symptomatic in only 37 percent of patients and always had a favorable outcome. Six cases of disseminated candidiasis were observed with fatal outcome in 3 cases. Ten patients had septicemia due to Gram positive germs with a favorable course in all cases. Two patients required retransplantation on the 2nd postoperative day because of primary graft failure. Three patients had hepatic infarction which was fatal in one case. Technical complications were represented by intra-abdominal bleeding in 3 cases, perihepatic hematoma in 10 cases and stenosis of the biliary anastomosis in 8 cases; in one patient, partial portal vein thrombosis occurred; no hepatic arterial thrombosis occurred during the first postoperative days but this complication was diagnosed later in 3 instances by arteriography. Five out of 7 patients transplanted for malignant liver disease experienced recurrence which cause death in 4 cases. In 3 out of the 5 patients transplanted for postviral B cirrhosis, chronic active hepatitis occurred 6 months after transplantation and one of these patients had to be retransplanted at 13 months for recurrence of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seventh Day Syndrome – acute hepatocyte apoptosis associated with a unique syndrome of graft loss following liver transplantationNote

Abstract: Aim: The aim of this study is to describe a unique 7th day syndrome (7DS), quite different from other causes of post‐transplantation allograft dysfunction in a group of orthotopic liver transplant (OLT) patients who needed retransplantation. Methods: A retrospective analysis of 594 consecutive OLT over an 8‐year period revealed that 10 patients developed allograft dysfunction approximately 7 days following an initially normal graft function. Results: The features included: (a) severe liver failure; (b) sudden peak of extremely high liver enzymes at approximately day 7; (c) serial liver biopsy findings of central lobular hemorrhage with minimal inflammatory cell infiltrate and (d) an explant with no evidence of vascular thrombosis. The biochemical and morphometric pathological data of these patients were compared with data of patitents who had early acute rejection (AR), hepatic artery thrombosis (HAT), primary non‐function (PNF), severe sepsis and no dysfunction. Lastly, serial liver core biopsies and explants were tested for evidence of apoptosis, which revealed a significantly higher number of apoptotic hepatocytes in 7DS compared to all control groups. Conclusions: Seventh Day Syndrome is a distinct entity associated with early graft dysfunction characterized by a marked apoptosis of hepatocytes. Fas receptor activation or other pathways of program cell death may be implicated in occurrence of 7DS.