bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of other organs recovered during in situ split-liver procurements
Authors: Ramcharan Thiagarajan , Glessing Brooke , Lake John R. , Payne William D. , Humar Abhinav
Published: August 2002

Split-liver transplantation is becoming a useful technique to expand the donor pool. Whether the split should be performed in situ or ex situ is not clear. One potential disadvantage of in situ splits is that prolonged surgical time and increased blood loss may negatively affect the function of other solid organs (kidneys, pancreas, and heart) procured from the same donor. Therefore, we studied the function of other organs posttransplantation. Between September 1, 1999, and March 31, 2000, we performed six in situ splits at the University of Minnesota (Minneapolis, MN). These six splits yielded six right-lobe liver grafts and six left-lobe liver grafts, which were transplanted into 12 adult-size recipients. Other grafts obtained from these six donors were as follows: kidney (n = 11), heart (n = 4), lungs (n = 1), pancreas (n = 2), and kidney-pancreas (n = 1). We then analyzed posttransplantation function of these grafts and the postoperative course of transplant recipients. All six donors were hemodynamically stable at the time of procurement. Mean donor age was 19.7 years. Mean surgical time for the procurement was 7.4 hours, with an average blood loss of 490 mL during in situ splitting of the liver. The 12 liver grafts showed good initial function with no primary nonfunction. The other organs also showed good function. Of 11 kidney recipients, only 1 patient developed delayed graft function, which resolved within 4 days. In addition, 1 kidney was lost early because of severe acute rejection. For the 10 recipients with functioning kidneys, mean creatinine level at hospital discharge was 2.0 mg/dL, and mean creatinine level after an average 9-month follow-up was 1.3 mg/dL. Of the 4 heart transplant recipients, 3 patients had good graft function immediately posttransplantation, with an ejection fraction greater than 60%, minimal inotropic requirements, and no surgical complications. The fourth heart transplant recipient, a critically ill status 1 patient, had poor initial function and a prolonged intensive care unit stay. At hospital discharge, pancreas and pancreas-kidney transplant recipients were all insulin free, with good urine amylase levels, no surgical or infectious complications, and no evidence of significant pancreatitis posttransplantation. The kidney of the pancreas-kidney transplant recipient functioned immediately; creatinine level after 7 months of follow-up was 1.2 mg/dL. Despite increased surgical time and blood loss, in situ splitting of liver grafts can be accomplished in stable donors without significant negative effects on other organs.
Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect
Authors: Molenaar Quintus I. , Legnani Cristina , Groenland Theo H.N. , Palareti Gualtiero , Begliomini Bruno , Terpstra Onno T. , Porte Robert J.
Published: August 2002

Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation (fibrinogen level, activated partial thromboplastin time [aPTT], prothrombin time, and platelet count) and fibrinolytic variables (tissue-type plasminogen activator [tPA] antigen and activity, plasminogen activator inhibitor activity, and D-dimer), as well as thromboelastography (reaction time [r], clot formation time, and maximum amplitude) in 27 patients administered either high-dose aprotinin (2 × 106 kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 × 106 KIU/h, and 1 × 106 KIU before reperfusion; n = 10), regular-dose aprotinin (2 × 106 KIU at induction and continuous infusion of 0.5 × 106 KIU/h; n = 8), or placebo (n = 9) during OLT. Blood samples were drawn at seven standardized intraoperative times. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dimer and tPA antigen levels) was significantly lower in aprotinin-treated patients compared with the placebo group. Interestingly, coagulation times (aPTT and r) were significantly more prolonged in aprotinin-treated patients than the placebo group. No difference was seen in the incidence of perioperative thrombotic complications in the entire study population (n = 137). Aprotinin has an anticoagulant rather than a procoagulant effect. Its blood-sparing (prohemostatic) effect appears to be the overall result of a strong antifibrinolytic and a weaker anticoagulant effect. These findings argue against a prothrombotic effect of aprotinin in patients undergoing OLT.
Selection criteria for liver transplantation in early-stage hepatocellular carcinoma with cirrhosis: Results of a multicenter study
Authors: Figueras Juan , Ibañez Luis , Ramos Emilio , Jaurrieta Eduardo , Ortiz-de-Urbina Jorge , Pardo Fernando , Mir José , Loinaz Carmelo , Herrera Luis , López-Cillero Pedro , Santoyo Julio
Published: August 2002

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.
Seasonal pattern of early mortality and infectious complications in liver transplant recipients
Authors: Singh Nina , Wagener Marilyn M. , Gayowski Timothy
Published: August 2002

Seasonal variation has been documented in the frequency and attributable mortality of a number of medical illnesses and infections in the nontransplantation setting. Whether similar trends exist in transplant recipients is not known. Seasonal rates of overall and early mortality and contributory variables stratified by season were assessed in 190 consecutive liver transplant recipients who underwent transplantation over a 10-year period. The frequency of infectious complications and rejection was also assessed and stratified by season of transplantation. Early (deaths occurring in the first year posttransplantation), but not overall, mortality correlated significantly with seasonality. Of patients with early mortality, 43% (13 of 30 patients) died in winter; 23% (7 of 30 patients), in spring; 13% (4 of 30 patients), in summer; and 20% (6 of 30 patients), in fall. The frequency of deaths in winter was significantly greater than for all other seasons (P = .022). The high wintertime mortality could not be explained by previously recognized risk factors portending a poor outcome, e.g., United Network for Organ Sharing status, Child-Pugh score, surgical time, blood loss, pretransplantation and posttransplantation dialysis, infections, rejection, or increased immunosuppression. Strong trends toward a higher rate of cytomegalovirus disease in patients who underwent transplantation in fall (P = .09) and bacterial infections in those who underwent transplantation in winter were documented (P = .09). There was no correlation between seasonality and rejection. Early mortality in winter in liver transplant recipients was significantly greater than if the deaths were totally random. Whether the seasonal clustering of deaths and infections is triggered by respiratory viruses, yet unrecognized viruses, or unknown exogenous factors remains to be determined.
Combined therapy with interferon and low-dose ribavirin in posttransplantation recurrent hepatitis C: A pragmatic study
Authors: Alberti Alberto Battista , Belli Luca Saverio , Airoldi Aldo , de Carlis Luciano , Rondinara Gianfranco , Minola Ernesto , Vangeli Marcello , Cernuschi Alessandra , D’Amico Maria , Forti Domenico , Pinzello Giovambattista
Published: August 2002

Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combination treatment with interferon (IFN) and ribavirin have been promising, but long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monotherapy in 18 patients with moderate to severe recurrent hepatitis C and a median follow-up of 32 months after the completion of combined therapy. All patients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), and 8 patients were also hepatitis C virus RNA negative in serum (virological ETR, 44%) at the end of combined treatment. At last follow-up after the completion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained response [LT-SR], 72%), and 5 patients also maintained viral clearance (virological LT-SR, 27%). Comparison of liver biopsy specimens before and after 12 months of combined therapy showed improvement in grading scores of at least two points in the majority of the patients (73%). Notably, a trend toward fibrotic progression was only noted in nonresponders. Regarding side effects, despite the low dose of ribavirn, almost half the patients developed hemolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that combined therapy with low-dose ribavirin followed by long-term ribavirin monotherapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.
Living donor liver transplantation for children with liver failure and concurrent multiple organ system failure
Authors: Mack Cara L. , Ferrario Mario , Abecassis Michael , Whitington Peter F. , Superina Riccardo A. , Alonso Estella M.
Published: August 2002

Liver transplantation for pediatric patients in liver failure and multiple organ system failure (MOSF) often results in poor patient survival. Progression of organ failure occurs while awaiting a cadaveric allograft. Therefore, we considered living donor liver transplantation (LDLT) in this critically ill group of children and report our initial results with comparison to a similar group who received cadaveric donation (CAD). A retrospective chart review was performed on all pediatric liver transplant recipients who met criteria for MOSF at the time of transplantation. Data collection involved pretransplantation patient profiles, as well as postoperative complications and patient survival. Eight patients in MOSF received living donor transplants and 11 patients received a cadaveric allograft. Mean wait time was 3.5 days in the LDLT group and 6.5 days in the CAD group. Pretransplantation patient profiles and postoperative complications were similar between groups. Mean cold ischemia times were 3.8 hours in the LDLT group and 7.9 hours in the CAD group (P = .0002). Thirty-day and 6-month survival rates of the LDLT group were 88% and 63% compared with 45% and 27% in the CAD group, respectively. Living donor transplant recipients in MOSF had decreased wait times to transplantation, as well as decreased cold ischemia times, compared with cadaveric transplant recipients. Patients in the LDLT group had markedly improved survival compared with the CAD group. Timely transplantation before worsening organ failure may account for these findings.
Functional venous anatomy for right-lobe grafting and techniques to optimize outflow
Authors: Marcos Amadeo , Orloff Mark , Mieles Luis , Olzinski Ann T. , Renz John F. , Sitzmann James V.
Published: August 2002

Right-lobe living donor liver transplantation has emerged as an alternative to cadaveric transplantation. An appreciation of the unique anatomy and behavior of the right lobe has emerged and has precipitated technical modifications. Living donors underwent right lobectomy, including preservation of significant inferior hepatic veins. The parenchyma was divided following a plane approximating the right border of the posterior two thirds of the midhepatic vein (MHV), but deviating anteriorly to include the distal one third of the MHV with the graft. Large venous tributaries from segment VIII were preserved. Anastomosis in the recipient was accomplished by means of complete cavoplasty. Significant inferior veins, tributaries to the MHV, and the distal portion of the MHV were reconstructed when technically possible. Forty-eight right-lobe resections and transplantations were performed in the manner described. There were no donor complications attributable to the technique. Forty-six of the 48 recipients are alive, and 44 of the 46 surviving patients have their original graft. Venous tributaries from segment VIII and/or the distal portion of the MHV were reconstructed in only 3 patients. Outflow obstruction was recognized intraoperatively in 2 patients; 1 patient had a caval web excised and the other patient required revision of the main anastomosis. Neither organ was lost. There were no other significant venous complications. The incidence of ascites was the same as that in recipients of whole organs. These methods of parenchymal transection and venous reconstruction resulted in a low rate of complications. The wide anastomosis and collateral pathways between the MHV and right hepatic vein seem to be more critical than reconstruction of tributaries from segment VIII or the distal MHV.
Hypertension and renal dysfunction in long-term liver transplant recipients
Authors: Gonwa Thomas A.
Published: August 2002

Key Points
Posttransplantation care: Role of the primary care physician versus transplant center
Authors: McCashland Timothy M.
Published: August 2002

Key Points
Bone disease after liver transplantation
Authors: Crippin Jeffrey S.
Published: August 2002

Key Points
Management of biliary problems after liver transplantation
Authors: Moser Michael A.J. , Wall William J.
Published: August 2002

Key Points
Contraception and pregnancy after liver transplantation
Authors: Riely Caroline A.
Published: August 2002

Key Points
Decreased splanchnic oxygen uptake and increased systemic oxygen uptake in cirrhosis are normalized after liver transplantation
Authors: Tietge Uwe J.F. , Bahr Matthias J. , Manns Michael P. , Böker Klaus H.W.
Published: August 2002

The aim of this study is to (1) characterize the impact of orthotopic liver transplantation (OLT) on splanchnic and systemic oxygen uptake (Vo2) in patients with liver cirrhosis, and (2) investigate possible influencing factors, as well as metabolic consequences, of reduced splanchnic Vo2 in patients with cirrhosis. Therefore, we measured systemic Vo2 (indirect calorimetry), portal pressure (hepatic venous pressure gradient), hepatic blood flow (HBF; primed continuous infusion of indocyanine green), and hepatic turnover (arteriohepatic venous concentration differences multiplied by HBF) of oxygen, glucose, free fatty acids (FFAs), and aromatic amino acids (AAAs) in 52 patients with advanced cirrhosis and 16 patients with a clinically stable long-term course after OLT. Systemic Vo2 was significantly increased in patients with cirrhosis (261 ± 7 mL/min) and normalized after OLT (216 ± 8 mL/min; P < .001). Arterial and hepatic venous oxygen saturation and splanchnic oxygen extraction (in percent) were not different between patients with cirrhosis and after OLT. Splanchnic Vo2 was decreased in patients with cirrhosis (41 ± 3 mL/min, representing 16% ± 1% of systemic Vo2) and normalized after OLT (69 ± 6 mL/min; P < .001, representing 32% ± 3% of systemic Vo2; P < .001). In patients with cirrhosis, a decrease in HBF was associated with decreased splanchnic Vo2 (r = 0.74; P < .001). Conversely, decreased splanchnic Vo2 reflected a decrease in hepatic glucose production (r = 0.34; P = .01) and hepatic extraction of FFAs (r = 0.40; P < .01) and AAAs (r = 0.30; P < .05). These results show that (1) splanchnic and systemic Vo2 normalize after OLT, indicating correction of hepatic and extrahepatic metabolic derangements; (2) in cirrhosis, HBF becomes limiting for hepatic oxygen supply; and (3) impaired splanchnic Vo2 reflects a decrease in metabolic liver function.
Posttransplantation growth in pediatric liver recipients
Authors: Renz John F. , de Roos Marnix , Rosenthal Philip , Mudge Christine , Bacchetti Peter , Watson Jessica , Roberts John P. , Ascher Nancy L. , Emond Jean C.
Published: August 2002

The aim of this retrospective analysis was to evaluate the growth of 96 pediatric liver transplant recipients from February 1988 to June 1999. Inclusion criteria were the following: age younger than 18 years, follow-up longer than 1 year, transplantation for a nontumor indication, and no retransplantation. Linear height and growth velocity SD scores were correlated to age, sex, indication for transplantation, immunosuppression, and graft type. Transplant recipients of all ages and indications and both sexes were growth retarded at transplantation. Recipients aged younger than 24 months showed growth within the first year to achieve a height distribution equal to that of an age-matched population. Posttransplantation growth inversely correlated with height standard score at transplantation. Children older than 2 years at transplantation established new growth curves, but remained growth retarded. As children approached the prepubertal growth acceleration, growth deficits frequently were erased. Transplant recipients with biliary atresia and α1-antitrypsin deficiency showed increased growth performance compared with those who underwent transplantation for chronic hepatitis or fulminant hepatic failure. Boys were less growth retarded at transplantation and showed improved posttransplantation growth performance versus girls. No correlation to immunosuppression or graft type was identified. We conclude that early transplantation of children who show growth retardation is optimal for restoration of growth potential, whereas delaying transplantation in older children impedes potential growth.
Anti-Interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation
Authors: Nelson David R. , Soldevila-Pico Consuelo , Reed Alan , Abdelmalek Manal F. , Hemming Alan W. , van der Werf Willem J. , Howard Richard , Davis Gary L.
Published: August 2002

The pathogenesis of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is poorly understood, but the cellular immune response is likely to have a major role. Daclizumab, an interleukin-2 receptor (IL-2R) antibody that blunts T-cell activation, leading to a decreased risk for cellular rejection, is used frequently in transplant recipients. The aim of this study is to evaluate the effect of daclizumab therapy on the incidence and severity of recurrent HCV. Forty-one liver transplant recipients (21 patients, HCV positive; 20 patients, HCV negative) at high risk for neurological or renal complications of calcineurin inhibitors were administered daclizumab, mycophenolate mofetil (MMF), and steroids in the early post-LT period, followed by tacrolimus and a steroid taper. All patients were followed up prospectively for graft function and disease recurrence with protocol liver biopsies day 7, month 4, and yearly. Compared with patients without HCV, patients with HCV administered daclizumab had greater 4-month serum alkaline phosphatase, total bilirubin, and alanine aminotransferase (ALT) levels. These biochemical differences resolved by 12 months, except for persistent elevation of ALT levels. Compared with a well-matched HCV control population, patients with HCV administered daclizumab were more likely to have an earlier onset of hepatitis, jaundice, and greater histological activity. Recurrent hepatitis progressed more rapidly in the daclizumab group; 45% developed advanced disease within 1 year. HCV viral load in the daclizumab group was significantly greater at both 4 months and 1 year. Results of this study suggest that the use of adjuvant IL-2R antibodies in combination with MMF in the early peritransplantation period may be associated with early recurrence of hepatitis C and more rapid histological progression of disease.
Obesity and the liver transplant recipient
Authors: Pruett Timothy
Published: August 2002

Abstract

Objective:

Severely obese patients who undergo orthotopic liver transplantation are likely to have higher morbidity, mortality, costs, and a lower long-term survival.

Methods:

This case-control study was done at a university hospital. One hundred twenty-one consecutive patients who underwent liver transplantation between 1994 and 1996 were studied. Severe obesity was defined as body mass index (BMI) more than 95th percentile (>32.3 for women and >31.1 for men), and moderate obesity was defined as BMI between 27.3 and 32.3 for women and 27.8 and 31.1 for men. The outcome measures were intraoperative complications, postoperative complications (wound infections, bile leak, vascular complications), length of hospital stay, costs of transplantation, and long-term survival.

Results:

The baseline characteristics, UNOS status, and cause of liver disease at the time of transplantation were similar in severely obese (n = 21, BMI = 37.4 ± 4.8 kg/m2), obese (n = 36, BMI 28.7 ± 0.9 kg/m2), and nonobese patients (n = 64, BMI 23.8 ± 2.5 kg/m2). The intraoperative complications and transfusion requirements were similar in all three groups. The postoperative complications such as respiratory failure (p = 0.009) and systemic vascular complications (p = 0.04) were significantly higher in severely obese patients. The overall perioperative complication rate was 0.61 (39 of 64 patients) in nonobese patients, 0.77 (28 of 36 patients) in obese patients, and 1.43 (30 of 21 patients) in severely obese patients (p = 0.01). Infections were the leading cause of death in all groups accounting for 57-66% of deaths. The length of hospital stay was significantly higher in obese patients. The hospital costs of transplantation were higher ($30,000-$40,000) in severely obese patients than in nonobese patients. The long-term patient survival was similar between the groups (Kaplan-Meier analysis).

Conclusions:

Despite higher postoperative complications, severely obese patients have an acceptable long-term survival, which is comparable to nonobese patients. The cost of transplantation is higher among severely obese patients. There was no increased incidence of cardiovascular mortality among severely obese patients during the follow-up period.
Hepatitis C quasispecies and severity of recurrence: Cause, consequence, or coincidence?
Authors: Rosen Hugo R. , Schwartz Jonathan M.
Published: August 2002

Recurrence of hepatitis C virus (HCV) infection after liver transplantation is almost universal and usually leads to chronic hepatitis with different degrees of severity. The pathogenic mechanisms underlying the variable outcome of HCV infection recurrence are not well defined, but recent data suggest that the dynamics of HCV quasispecies may be involved. HCV quasispecies evolution was traced by longitudinal single-strand conformation polymorphism, direct sequencing, and cloning analyses of pretransplant and posttransplant HCV-1b isolates from patients with histologically severe (seven cases) or mild or moderate (nine cases) HCV infection recurrence. Differences between the two groups of patients that concerned the level of viremia or the degree of HCV quasispecies complexity and diversity were not observed at any of the three time points analyzed. However, emergence of nucleotide and amino acid changes during the 12-month follow-up was significantly more frequent in patients with mild or moderate than in those with severe HCV infection recurrence. The ratio of nonsynonymous to synonymous nucleotide substitutions 12 months after transplantation was also greater in the former, suggesting that the HVR1 of HCV is under stronger selective pressure in these subjects. These findings suggest that the degree of amino acid diversification in the HVR1 of HCV, which probably reflects the strength of immune pressure on HCV, is inversely related to the histologic severity of HCV infection recurrence.
A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C
Authors: Jain Ashok , Kashyap Randeep , Demetris Anthony J. , Eghstesad Bijan , Pokharna Renu , Fung John J.
Published: August 2002

Hepatitis C is the most common indication for liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV) infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate mycophenolate mofetil (MMF), which has both immunosuppressive and antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to tacrolimus (TAC) and prednisone versus TAC, prednisone, and MMF therapy. The rate of recurrence of HCV, patient and graft survival, incidences of rejection, and histological findings were examined. Fifty six patients were randomized to TAC and steroid therapy (double [D] drug; group D), and 50 patients were randomized to TAC, steroid, and MMF therapy (triple [T] drug; group T). Liver biopsies were performed when liver function was abnormal; protocol liver biopsies were not performed. Mean follow-up was 4.3 ± 0.8 years. Actuarial patient survivals at 4 years were 72.6% in group D and 73.8% in group T (P = not significant). Actuarial graft survivals at 4 years were 65.6% in group D and 65.4% in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV. One patient in each group died of recurrent HCV without re-LT. Twenty-six patients in group D (46.4%) and 23 patients in group T (46.0%) showed signs of recurrent HCV. Mean hepatitis activity index (HAI) scores were 7.4 ± 2.7 in group D and 7.0 ± 3.4 in group T, and mean fibrosis scores were 2.9 ± 1.7 in group D and 2.6 ± 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period. None of these values reached statistical significance. Rates of HCV recurrence, graft loss or death from recurrent HCV, and 4-year actuarial patient and graft survival were not different between the groups. In liver transplant recipients with HCV, MMF has no impact on patient survival, graft survival, rejection, or rate of HCV recurrence based on biochemical changes and histological findings. In addition, there was no difference in HAI or fibrosis score between the two groups. Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting.
Results of liver transplantation for familial amyloid polyneuropathy type I in Brazil
Authors: Bittencourt Paulo Lisboa , Couto Claudia Alves , Farias Alberto Queiroz , Marchiori Paulo , Massarollo Paulo Celso Bosco , Mies Sérgio
Published: August 2002

Familial amyloid polyneuropathy type I (FAP-I) is an inherited amyloidosis secondary to systemic deposition of amyloid fibrils containing mutant transthyretin (TTR) variants. The disease has a progressive clinical course and is usually fatal 10 years after its onset. TTR is mainly produced in hepatocytes, and liver transplantation (LT) has been proposed as an effective treatment for FAP-I. The aim of this study is to evaluate the results of LT for FAP-I in Brazil and analyze prognostic factors associated with survival after surgery. Twenty-four patients (median age, 36 years; range, 25 to 52 years) who underwent LT with the diagnosis of FAP-I were evaluated. Surgery was uneventful in all but six patients who died of complications of primary liver nonfunction (n = 1), cardiogenic shock (n = 1), sepsis (n = 3), and hepatic artery thrombosis (n = 3). Overall 1- and 5-year survival rates were 70% and 58%, respectively. Most patients had stabilization or improvement of symptoms after a median follow-up of 36 months (range, 14 to 82 months). Survivors had a shorter disease duration before LT (median, 6 years; range, 2 to 17 years v 9 years; range, 7 to 12 years; P = .02), greater albumin levels (median, 4 g/dL; range, 3 to 4.7 g/dL v 3.6 g/dL; range, 2.6 to 4.1 g/dL; P = .03), and greater modified body mass index scores (median, 735; range, 502 to 1,432 v 659; range, 411 to 803; P = .04) compared with nonsurvivors. However, only disease duration and albumin levels were independently associated with survival in multivariate analysis. In conclusion, LT is an effective therapy for FAP-I. Mortality after surgery is associated with poor nutritional status and long-standing disease before LT. Thus, LT should be performed as early as possible after the onset of FAP-I symptoms to avoid major disability and improve survival.
Mast cell hyperplasia in chronic rejection after liver transplantation
Authors: O’Keeffe Cathal , Baird Alan W. , Nolan Niamh , McCormick Aiden P.
Published: August 2002

The pathogenesis of chronic hepatic allograft rejection is poorly understood. Recent studies suggested that hepatic mast cells may be involved in the pathogenesis of chronic cholestatic liver disease. Because chronic rejection after liver transplantation is predominantly a cholestatic process, the aim of this study is to determine whether hepatic mast cells are involved in its pathogenesis. Biopsy specimens from (1) normal livers (n = 5), (2) transplanted livers with end-stage chronic rejection (n = 8), and (3) transplanted livers with acute cellular rejection (mild, n = 7; moderate, n = 5; severe, n = 7) were studied. Biopsy specimens were stained immunohistochemically for mast cells with human antitryptase antibody. Mast cell density was significantly increased in the chronic-rejection group (4.9 ± 0.6/mm2) compared with controls (2.9 ± 0.5/mm2; P < .05). The percentage of portal tracts containing mast cells was significantly greater in chronic-rejection (89% ± 8%) than control biopsy specimens (69% ± 5%; P < .05), as was the average number of mast cells per portal tract (5.4 ± 0.9 v 1.9 ± 0.4 cells; P < .01). In chronic rejection, tissue mast cells frequently were seen surrounding damaged bile ducts in inflamed portal tracts. Neither mast cell density nor distribution was significantly different from controls in posttransplantation biopsy specimens with acute cellular rejection of mild, moderate, or severe degree. The finding of mast cells infiltrating portal tracts and surrounding damaged bile ducts in chronic rejection suggests that hepatic mast cells may be important effector cells in the pathogenesis of chronic rejection.
β-Galactosidase as a marker of ischemic injury and a mechanism for viability assessment in porcine liver transplantation
Authors: St. Peter Shawn D. , Imber Charles J. , De Cenarruzabeitia Inigo Lopez , Mcguire James , James Tim , Taylor Richard , Friend Peter J.
Published: August 2002

Glycohydrolases are a group of enzymes contained predominantly within lysosomes, which are released during Kupffer cell activation or death. One of these, β-galactosidase, has been proposed as a marker of ischemia-reperfusion injury in the liver because Kupffer cell activation represents a primary event in the injurious reperfusion cascade. In this study, we compared B-galactosidase with more traditional indicators of liver injury and function in a porcine model of liver preservation. Porcine livers were allocated into two groups: group C (n = 5), preserved in University of Wisconsin solution by standard cold storage for 24 hours, and group W (n = 5), perfused with oxygenated autologous blood on an extracorporeal circuit for 24 hours. Both groups were subsequently tested on the circuit during a 24-hour reperfusion phase. The perfusate was sampled for levels of β-galactosidase, as well as traditional markers of liver injury and function. A sharp increase in β-galactosidase levels was seen on reperfusion of cold preserved livers to a level of 1,900 IU/mL. This contrasted dramatically with normothermically preserved livers, in which the level never exceeded 208 IU/mL (P = .002). β-Galactosidase levels showed much earlier and greater increases compared with transaminase levels in livers injured by ischemia. A rapid elevation in β-galactosidase levels corresponded well with poor liver function and more liver injury. Measurement of β-galactosidase is a simple test that quantifies ischemia-reperfusion injury of preserved livers. It is more sensitive than transaminases, with faster and larger increases in levels after ischemic injury. It can be useful in assessing the viability of a liver during machine preservation.
Cavoportal hemitransposition: A successful way to overcome the problem of total portosplenomesenteric thrombosis in liver transplantation
Authors: Gerunda Giorgio E. , Merenda Roberto , Neri Daniele , Angeli Paolo , Barbazza Franco , Valmasoni Michele , Feltracco Paolo , Zangrandi Fabio , Gangemi Antonio , Miotto Diego , Gagliesi Alessandro , Faccioli Alvise Maffei
Published: August 2002

Orthotopic liver transplantation (OLT) may be feasible even in the presence of diffuse portal vein thrombosis (PVT) in the recipient, providing hepatopetal portal flow to the graft can be ensured. Cavoportal hemitransposition was used in selected cases in which no other salvage solutions were technically possible. We report our experience of two patients with diffuse thrombosis of the entire portal system. One patient also had thrombosis of a previous portacaval shunt with a synthetic interposition graft. Portal pedicle dissection and native hepatectomy (with or without vena cava removal) appeared difficult. Bleeding from the exposed area was severe, and in one case, a new laparotomy was necessary to stop the abdominal hemorrhage. The postoperative course was complicated by severe ascites (with fluid infection and surgically drained suprahepatic abscess in one case), renal insufficiency (requiring dialysis in one case), esophagogastric variceal bleeding (needing several sessions of endoscopic treatment), and bronchopneumonic infections (in one case, superinfection with Aspergillus fumigatus despite amphotericin B lipid complex therapy led to the patient’s death from multiorgan failure). Our experience was compared with 17 other cases in the literature. Etiologic factors, preoperative diagnostics, surgical problems, and postoperative complications are focused on and discussed. Diffuse PVT no longer appears to be an absolute contraindication to OLT, although cavoportal hemitransposition needs further experience and long-term follow-up.
Donor safety in living related liver transplantation: Underestimation of the risks for deep vein thrombosis and pulmonary embolism
Authors: Durand François , Ettorre Giuseppe Maria , Douard Richard , Denninger Marie-Hélène , Kianmanesh Alireza , Sommacale Daniele , Farges Olivier , Valla Dominique , Belghiti Jacques
Published: August 2002

Optimal safety for donors is a necessary condition for living related liver transplantation to expand. Although the risks for complications directly related to surgical intervention have been carefully evaluated, the extent and nature of other complications, such as pulmonary embolism, associated with living donation have not been clearly anticipated. We report a case of severe pulmonary embolism followed by ulcer-related upper digestive tract bleeding in an adult donor after right hepatectomy. In this donor, we found an unexpected predisposing coagulation disorder (increased von Willebrand factor activity) postoperatively. This finding led us to include systematic screening for coagulation disorders during evaluation of donors, a policy which led us thereafter to reject definitely or temporarily some candidates for donation. Although the cost-effectiveness of such investigations is not definitely established, we strongly recommend a specific approach to improve donor safety. In addition, we emphasize that the major complications observed in living donors should be systematically reported in an international database.
Immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients
Authors: Calmus Yvon , Scheele Johannes R. , Gonzalez-Pinto Ignacio , Jaurrieta Eduardo J. , Klar Ernst , Pageaux Georges P. , Scudamore Charles H. , Cuervas-Mons Valentin , Metselaar Herold J. , Prestele Hans , Girault Daniele
Published: August 2002

Acute graft rejection remains a major problem among additional sequelae in liver transplant recipients. Basiliximab, a chimeric monoclonal antibody with high affinity for the CD25 chain of the interleukin-2 receptor, has significantly reduced the incidence of acute rejection episodes in renal transplant recipients. This single-arm, open-label, multicenter study investigated the efficacy and tolerability of basiliximab immunoprophylaxis in adult patients undergoing first elective liver transplantation. One hundred one patients (70 hepatitis C virus [HCV]-negative patients, 31 HCV-positive patients) were administered basiliximab, 20 mg, by intravenous bolus injection the day of transplantation (day 0) and day 4. In addition, all patients were administered triple immunosuppressive therapy with cyclosporine, steroids, and azathioprine. The efficacy of basiliximab was assessed by conventional parameters, and tolerability was assessed by the incidence of adverse events, infections, and laboratory test result abnormalities. At 6 months, the incidence of first acute biopsy-confirmed rejection episodes was 22.8%. Rejections were more frequent in the HCV-positive (29.0%) than HCV-negative subgroup (20.0%; P = .441). No rejection episode was graded histologically as severe, and no patient required antibody therapy for the management of acute rejection. Ten patients (9.9%) required treatment with tacrolimus for acute rejection episodes. Patient and graft survival rates at 12 months were 90.1% and 88.1%, respectively. Basiliximab caused no injection-site reactions, anaphylaxis, or cytokine release syndrome. Five malignancies were reported at 12 months: of these, three malignancies predated transplantation surgery. Compared with earlier studies, the addition of basiliximab immunoprophylaxis to triple immunosuppressive therapy provides increased efficacy in reducing the incidence of acute rejection episodes, with no clinically significant increase in adverse events.
Living donor liver transplantation: Summary of a conference at The National Institutes of Health
Authors: Shiffman Mitchell L. , Brown Robert S. , Olthoff Kim M. , Everson Gregory , Miller Charles , Siegler Mark , Hoofnagle Jay H.
Published: August 2002

Living donor liver transplantation for adults was developed only recently in an attempt to increase the pool of donor organs; to reduce morbidity and mortality; and to improve the long-term survival of patients in need of liver transplant. Within a few brief years, this procedure has gained widespread support by both the public and transplant community. The procedure will soon be performed by nearly 80% of all liver transplant programs in the United States. Unfortunately, the long-term risks of the procedure to the recipient and especially the donor remain undefined. In response to the rapid growth and enthusiasm for this procedure, the National Institutes of Health sponsored a workshop, the goals of which were to review the scientific, medical, and nonmedical issues associated with living donor liver transplantation, and to define questions for future basic and clinical investigations which could improve the success and applicability of this procedure.
Outcome of liver transplantation for patients with pulmonary hypertension
Authors: Starkel Peter , Vera Alonso , Gunson Bridget , Mutimer David
Published: August 2002

It is generally believed that pulmonary hypertension (PHT) adversely affects outcome after liver transplantation (LT). Most transplant units consider severe PHT to be an absolute contraindication to LT. We examined the outcome of 145 patients who underwent LT between 1997 and 1999. Pulmonary artery pressures (PAPs) had been measured before surgery. Pre-LT workup included electrocardiography and echocardiography for the majority of patients. Also, the liver unit database was screened for patients with known PHT who had undergone LT before 1997. Based on pulmonary floatation catheter measurements made after the induction of anesthesia for LT, PHT was defined as mild or moderate to severe if the mean PAP (MPAP) exceeded 25 and 35 mm Hg, respectively. The incidence of PHT was 26% (38 of 145 patients); 31 of 38 patients had mild PHT. Kaplan-Meier survival analysis did not show a significant survival benefit for patients with normal PAPs compared with patients with PHT (all, mild, moderate to severe). For surviving patients, the duration of ventilation and intensive care unit stay was unaffected by PHT. Four of 5 patients (identified from the database 1982 to 1999) with MPAPs greater than 40 mm Hg survived LT by more than 1 year. PHT of this severity was usually associated with specific and suggestive abnormality of the echocardiogram. Mild PHT is common and does not affect patient outcome after LT. Moderate and severe PHT are uncommon. Our analysis suggests that when the cardiac index is preserved, the majority of patients with moderate and severe PHT can survive LT, and they will not die of PHT during long-term follow-up. Echocardiography detects most severe PHT, but not mild and moderate PHT.
Assessing health-related quality of life pre- and post-liver transplantation: A prospective multicenter study
Authors: Ratcliffe Julie , Longworth Louise , Young Tracey , Bryan Stirling , Burroughs Andrew , Buxton Martin
Published: August 2002

We report on a prospective multicenter study to assess pretransplantation and posttransplantation health-related quality of life (HRQL) of liver transplant recipients. HRQL was assessed at several timepoints using a self-completion questionnaire consisting of the EuroQol instrument (EQ-5D) and the 36-Item Short-Form Health Survey (SF-36) health status profile measure. All individuals selected to receive treatment as part of the UK NHS liver transplantation program at each of six liver transplantation centers in England and Wales during a 2-year period (n = 542) were eligible to be included on the study. An overall response rate of 84% (455 responses) was achieved. A paired comparison of HRQL at listing and 3 months posttransplantation showed statistically significant improvements (P < .05) in all dimensions of the SF-36 (with the exception of Bodily Pain [P = .686]) and the EQ-5D tariff and visual analogue scale (VAS) scores. An analysis of posttransplantation HRQL over time for patients who survived until the end of the study (24 months posttransplantation) showed a statistically significant improvement (P < .05) for all dimensions of the SF-36 (apart from Mental Health [P = .245] and Role-Emotional dimensions [P = .265]) and the EQ-5D VAS and tariff scores. Adjusting for patients who died posttransplantation reduced mean EQ-5D tariff scores substantially, and the change over time in EQ-5D tariff scores was no longer statistically significant (P = .55). Results of regression analysis conducted to assess the importance of patient characteristics and center size on EQ-5D tariff and VAS scores generated posttransplantation indicated there was variation in scores according to patient age and center size.
Body surface area and body weight predict total liver volume in Western adults
Authors: Vauthey Jean-Nicolas , Abdalla Eddie K. , Doherty Dorota A. , Gertsch Philippe , Fenstermacher Marc J. , Loyer Evelyne M. , Lerut Jan , Materne Roland , Wang Xuemei , Encarnacion Arthur , Herron Delise , Mathey Christian , Ferrari Giovanni , Charnsangavej Chuslip , Do Kim-Anh , Denys Alban
Published: August 2002

Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = −794.41 + 1,267.28 × BSA (square meters; r
2 = 0.46; P < .0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 × weight (kilograms; r
2 = 0.49; P < .0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.