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R W Busuttil

Publications and source records attributed to R W Busuttil.

At least 91 records · Page 5Linked to original sources
PubMed1998

Significance of early aminotransferase elevation after liver transplantation.

BACKGROUND: We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome. METHODS: The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates. RESULTS: Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI. CONCLUSIONS: We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.

Adult↗
PubMed1998

Liver transplantation for fulminant hepatic failure in the pediatric patient.

OBJECTIVE: To review the clinical characteristics, outcomes, and risk factors for survival among 57 pediatric patients undergoing orthotopic liver transplantation for fulminant hepatic failure at the University of California, Los Angeles, Center for the Health Sciences. DESIGN: The medical records of 57 consecutive pediatric patients undergoing orthotopic liver transplantation for fulminant hepatic failure from July 1, 1984, to June 25, 1997, were reviewed and survival data were analyzed via univariate and multivariate statistical methods. The type and incidence of posttransplant complications were determined as was the quality of long-term graft function. Median follow-up period was 3.38 years (range, 0-10.02 years). RESULTS: The 1-, 3-, and 5-year actuarial patient survival rates were 77%, 77%, and 77%, respectively, while graft survivals were 73%, 65%, and 65%. Stepwise Cox regression analysis revealed that recipient age and ventilator dependency at the time of transplantation were independently and significantly correlated with patient survival, whereas no association was found between survival and grade of encephalopathy, prior abdominal surgery, recipient weight, pretransplantation values for total bilirubin or prothrombin time, ABO match, allograft type, peak posttransplantation aspartate aminotransferase levels, or the presence of posttransplantation hepatic artery thrombosis. Non-ventilator-dependent patients demonstrated a 96% 1-, 3-, and 5-year survival as compared with only 56% at these same time points for those children requiring ventilator support at the time of transplantation (P < .001). At the time of most recent follow-up, median values for total bilirubin and aspartate aminotransferase concentrations were 10.3 micromol/L (0.6 mg/dL) and 56 U/L, respectively, in the 40 surviving patients. CONCLUSIONS: In children undergoing liver transplantation for fulminant hepatic failure: (1) overall results are comparable to those achieved for less emergent non-neoplastic indications in this same age group; (2) ventilator dependency prior to transplantation is the strongest predictor of ultimate survival, followed by recipient age; (3) 5-year survival exceeds 90% in recipients who are ventilator independent immediately prior to liver transplantation but is significantly compromised once the need for mechanical ventilation supervenes, particularly in those younger than 4 years; and (4) prompt referral and timely liver replacement are the cornerstones of optimal outcome.

Actuarial Analysis↗
PubMed1998

Prophylaxis against hepatitis B recurrence following liver transplantation using combination lamivudine and hepatitis B immune globulin.

Patients undergoing liver transplantation for hepatitis B-related liver disease are prone to recurrence. The mainstay of prophylaxis has been passive immunotherapy with hepatitis B immune globulin (HBIG). Antiviral therapy with lamivudine has proven effective in lowering hepatitis B virus (HBV) DNA and improving histology in patients with hepatitis B infection; its role in prophylaxis against hepatitis B recurrence following liver transplantation is under investigation. Viral breakthrough and resistance, however, are a significant problem with monotherapy with either HBIG or lamivudine. The efficacy of combination lamivudine/HBIG prophylaxis has not been reported. Fourteen patients underwent transplantation for decompensated liver disease owing to hepatitis B. Lamivudine (150 mg p.o./d) was begun before transplantation in 10 patients, including 4 who were HBV DNA-positive. In addition, 1 patient was HBV DNA-positive when transplanted. HBIG was given perioperatively and continued thereafter; treatment with lamivudine was maintained or initiated at the time of transplantation and continued indefinitely. The median follow-up was 387 days. Actuarial 1-year patient and graft survival was 93% (1 patient died of unrelated causes). At a median interval of 28 days following lamivudine treatment, all 5 HBV DNA-positive patients cleared HBV DNA from the serum; 1 went on to clear hepatitis B surface antigen (HBsAg), before transplantation, at day 148 of lamivudine treatment. By the highly sensitive polymerase chain reaction (PCR), at a median of 346 days (range, 130-525 days) following transplantation, all 13 surviving patients had no detectable serum HBV DNA. Lamivudine suppresses HBV replication in patients awaiting liver transplantation. At a median follow-up of 1.1 years, combination prophylaxis with lamivudine and HBIG prevented hepatitis B recurrence following liver transplantation.

Adult↗
PubMed1998

Successful treatment of mycotic hepatic artery pseudoaneurysms with arterial reconstruction and liposomal amphotericin B.

A 55-year-old woman developed end-stage liver disease and the hepatorenal syndrome secondary to cryptogenic cirrhosis. Orthotopic liver transplantation was complicated by bile peritonitis, requiring reoperation and eventual placement of an internal biliary stent. On postoperative day 26, hemobilia was caused by localized rupture of mycotic (Aspergillus fumigatus) hepatic artery pseudoaneurysms with fistulization into the biliary tree. After arterial reconstruction with a reversed autologous saphenous vein graft, the patient was treated successfully with liposomal amphotericin B.

Amphotericin B↗
PubMed1998

The role of orthotopic liver transplantation in the treatment of ornithine transcarbamylase deficiency.

The purpose of this study was to combine our clinical experience with a review of the literature to determine the value of orthotopic liver transplantation in the treatment of both boys and girls with ornithine transcarbamylase deficiency. Three boys younger than 1 year of age with symptomatic ornithine transcarbamylase deficiency (median age, 116 days; range, 40 to 223 days) underwent orthotopic liver transplantation. The patients' growth, developmental progress, ammonia levels, and amino acid levels were analyzed pre- and post-liver transplantation. The clinical courses of the respective patients and the treatment modalities used were compared with published reports from 1978 through 1997. The median follow-up period in these 3 patients was 3.2 years (range, 9 months to 5.2 years). Orthotopic liver transplantation restored normal urea production and stabilized ammonia levels within 24 hours of surgery (median serum ammonia level 24 hours post-liver replacement, 43 micromol/L; range, 30 to 66 micromol/L). After liver replacement, arginine synthesis was normalized; however, plasma citrulline levels remained less than normal in all patients. Linear growth was evaluated in all 3 patients at the time of the most recent follow-up; median z scores for patient height and weight were -2.16 and -1.16, respectively. Standardized intelligence tests showed that 2 of the 3 patients continue to perform at age-appropriate levels. The third child was developmentally delayed pretransplantation at 4 months of age on presentation and continues to perform in a below-average fashion. Orthotopic liver transplantation results in the restoration of normal urea production and serum ammonia levels in the boy suffering from symptomatic ornithine transcarbamylase deficiency. Serum arginine, but not citrulline, levels are normalized, probably because of the persistent intestinal mucosa defect. Patient growth is similar to that in infants undergoing liver transplantation for other causes. When liver transplantation is performed before cognitive impairment occurs, intellectual development is normal, because the risk of additional episodes of hyperammonemia is elevated.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Efficacy and safety of heat exchanger added to venovenous bypass circuit during orthotopic liver transplantation.

Hypothermia during orthotopic liver transplantation (OLT) is common despite measures to prevent this complication. We retrospectively analyzed two groups of patients; those managed with (n = 113) or without (n = 109) a heat exchanger (HE) incorporated in the venovenous bypass (VVB) circuit to test the hypothesis that normothermia before liver reperfusion minimizes hypotension during reperfusion and decreases neohepatic transfusion requirements. Use of the HE resulted in significantly warmer patients during reperfusion and at the end of surgery (P < .001). An increase in neohepatic transfusion requirement was observed in patients with HE use: packed red blood cells, 4 +/- 4 versus 3 +/- 3 units; fresh-frozen plasma, 5 +/- 5 versus 4 +/- 4 units; platelets, 8 +/- 8 versus 6 +/- 7 units; and cryoprecipitate, 5 +/- 7 versus 3 +/- 5 units. There was no difference between the two groups in the untoward hemodynamic events during reperfusion of the liver (P = .31). We conclude that during OLT, the use of an HE in a nonheparinized VVB circuit helps maintain normothermia. Our limited experience suggests that its use is safe but does not improve hemodynamic stability during reperfusion or decrease blood loss during the neohepatic period.

Chi-Square Distribution↗
PubMed1998

Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin glycoprotein ligand-1.

OBJECTIVE: The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ. METHODS: To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events. RESULTS: In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.

Animals↗
PubMed1998

Long-term results of pediatric liver transplantation: an analysis of 569 transplants.

OBJECTIVE: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

Actuarial Analysis↗
PubMed1998

Resolution of recurrent hepatitis B in two liver transplant recipients treated with famciclovir.

Recurrent hepatitis B infection after orthotopic liver transplantation remains problematic despite prophylaxis with hepatitis B immune globulin (anti-HBs IgG). Recently, famciclovir (an oral nucleoside analog) has been shown to have potent antiviral activity against hepatitis B in vitro as well as in patients with chronic hepatitis B. We present two patients who developed recurrent hepatitis B after orthotopic liver transplantation and were treated with famciclovir, 500 mg t.i.d. Both patients subsequently responded with marked improvement in biochemical liver tests and histology, with subsequent loss of hepatitis B surface antigen. Famciclovir is a useful agent in the treatment of hepatitis B in the liver transplant recipient.

2-Aminopurine↗
PubMed1998

Fifteen-year experience with adult and pediatric liver transplantation at the University of California, Los Angeles.

In the past 6 years, advances in surgical technique and immunosuppression regimens have improved overall survival of transplant patients. Hepatitis C and alcoholic cirrhosis are the most common indications for transplantation at this center in the adult population while biliary atresia remains the most common indication in children. Organ shortages remain the most formidable obstacle to widespread application of organ transplantation. As recipient indications and criteria for transplantation expand, the number of patients awaiting organs increases. Simultaneously, donor criteria has not expanded and overall donor numbers have not increased substantially. We have used several approaches to alleviate the shortage of organs for both adults and children. Living-related donor transplantation yields excellent results and the operation can be done in an elective setting; however, it places an otherwise healthy person at risk. It is justified on basis of good results and the present shortage of organs. In-situ split-liver transplantation presents the opportunity to transplant children with size-matched organs without reducing the adult cadaveric pool. It is limited by the technical expertise required to perform the procedure safely. It can reduce the need to resort to living donor transplantation and is routinely used as the first option for pediatric patients awaiting transplantation at UCLA. Our results show that good results can be achieved with strict donor and recipient selection. In situ splitting has had a substantial impact on decreasing the pediatric waiting list time at our institution. Small bowel transplantation results have been improving; however, the complications related to the heavy immunosuppressive regimens need to be resolved.

Adult↗
PubMed1997

Long-term ganciclovir prophylaxis for successful prevention of primary cytomegalovirus (CMV) disease in CMV-seronegative liver transplant recipients with CMV-seropositive donors.

BACKGROUND: We conducted a trial of long-term ganciclovir prophylaxis for prevention of primary cytomegalovirus (CMV) disease in CMV-seronegative liver transplant recipients with CMV-seropositive donors. METHODS: Patients received intravenous ganciclovir at a dose of 6 mg/kg once a day from day 1 to day 30 after transplant, and then at a dose of 6 mg/kg once a day, Monday through Friday, until day 100. Forty-seven consecutive patients were evaluated. Due to the primary physician's decision or administrative error, 10 patients received less than 7 weeks of ganciclovir (mean duration, 3 weeks). RESULTS: Four of the 10 (40%) patients who received less than 7 weeks of ganciclovir developed CMV disease (hepatitis). In contrast, none of the 37 patients given 100 days of prophylactic ganciclovir developed CMV disease while receiving ganciclovir. Two patients (5.4%) subsequently developed CMV disease (hepatitis) 21 and 88 days, respectively, after completing their ganciclovir prophylaxis. Reversible neutropenia in three patients (8.1%) was the only side effect associated with long-term ganciclovir. Complications from central intravenous catheters did not occur. CONCLUSIONS: These results reaffirm the efficacy and safety of long-term ganciclovir prophylaxis for prevention of primary CMV disease in a large number of high-risk CMV-seronegative liver transplant recipients with CMV-seropositive donors.

Adolescent↗
PubMed1997

In situ splitting of the cadaveric liver for transplantation.

BACKGROUND: The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation. METHODS: This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors. RESULTS: The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis CONCLUSIONS: In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.

Actuarial Analysis↗
PubMed1997

Randomized controlled trial to evaluate flush and reperfusion techniques in liver transplantation.

To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.

Adult↗