Pulsatile Hematuria From Procurement Core Needle Biopsy: A Case Report.

Core needle biopsies are still widely performed to evaluate the pathologic suitability of a kidney allograft. Here, we report a case of pulsatile hematuria from a procurement core needle biopsy where the patient had to be taken emergently to interventional radiology for coil embolization immediately after organ reperfusion.

Academic careers and lifestyle characteristics of 171 transplant surgeons in the ASTS.

This manuscript reports the demographics, education and training, professional activities and lifestyle characteristics of 171 members of the American Society of Transplant Surgeons (ASTS). ASTS members were sent a comprehensive survey by electronic mail. There were 171 respondents who were 49 ± 8 years of age and predominantly Caucasian males. Female transplant surgeons comprised 10% of respondents. ASTS respondents underwent 15.6 ± 1.0 years of education and training (including college, medical school, residency and transplantation fellowship) and had practiced for 14.7 ± 9.2 years. Clinical practice included kidney, pancreas and liver organ transplantation, living donor surgery, organ procurement, vascular access procedures and general surgery. Transplant surgeons also devote a significant amount of time to nonsurgical patient care, research, education and administration. Transplant surgeons, both male and female, reported working approximately 70 h/week and a median of 195 operative cases per year. The anticipated retirement age for men was 64.6 ± 8.6 and for women was 62.2 ± 4.2 years. This is the largest study to date assessing professional and lifestyle characteristics of abdominal transplant surgeons.

Preservation of recipient middle hepatic vein for drainage of anterior sector veins in adult-to-adult living-donor liver transplantation.

The inclusion of donor middle hepatic vein (MHV) in right-lobe living-donor grafts and the need for reconstruction of the MHV tributaries have long been controversial areas in living-donor liver transplantation. We report technical details in restoration of venous drainage of the anterior sector (segments V and VIII) of the right lobe of the liver graft using a preserved MHV from the recipient liver, and address the issue of reconstruction of donor MHV tributaries without use of an interposition graft. We review clinical situations in which restoration of outflow drainage of the anterior segment of the liver graft should be considered.

Open abdomen management with human acellular dermal matrix in liver transplant recipients.

BACKGROUND: Abdominal wall closure after liver transplantation is not always feasible and may result in increased intra-abdominal pressure along with associated complications. Various temporary closure techniques as well as open wound management have been used to address this complex problem. The aim of this series was to describe an approach to definitive wound closure of the open abdomen in liver transplant patients. METHODS: We performed a retrospective review of all liver transplant patients at our institution from September 2005 to November 2007. The management of the open abdomen in 10 liver transplant patients was reviewed, and a novel approach described to manage these defects. RESULTS: Ten patients with open wounds were closed during the study period using human acellular dermal matrix (HADM). There were 7 men and 3 women of median age 55 years. Average size of HADM was 235 cm(2). The median follow-up is 10 months with no incidence of evisceration or hernia. In 1 patient, the graft failed along the lateral side due to infection; it dislodged during vacuum-assisted closure dressing change in another patient at 5 months after closure. Fascial closure was not possible due to organ edema (n = 3), a large liver (n = 4) or wound infection with dehiscence (n = 3). CONCLUSIONS: HADM can be used for primary wound closure in both clean and contaminated wounds as an alternative to an open abdomen post-liver transplantation.

Leukemia after liver transplant.

INTRODUCTION: Acute leukemia is rare after solid organ transplantation. METHODS: Review of data on 3 patients with acute leukemia identified among 1365 who underwent liver transplantation at our center, and a review of the literature. RESULTS: In patient 1, AML-M4 developed 19 months after transplant for cryptogenic cirrhosis. In patient 2, B cell acute lymphoid leukemia was diagnosed 10 months after liver transplant for fulminant hepatitis. Both patients had normal cytogenetics, and achieved complete remission with chemotherapy. In patient 3, acute monocytic leukemia-M3 with t(15;17) arose 18 months after transplant for hepatitis C cirrhosis. This patient received treatment with retinoic acid and chemotherapy, but developed a disseminated intravascular coagulation and died before completing therapy. No patient presented with chromosomal abnormalities commonly seen in secondary leukemia. The latency period to diagnosis after transplant was 10-19 months. CONCLUSIONS: Acute leukemia, although rare after liver transplantation, should be considered in the differential diagnosis of hematological complications.

Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient's disease.

The aim of this study is to analyze the impact of the recipient's disease severity on graft size requirements and outcome in adult-to-adult living donor liver transplantation. A limiting factor in adult-to-adult living donor liver transplantation has been adequacy of graft size. A minimal graft-recipient weight ratio (GRWR) of 0.8% to 1% has been suggested, without taking the recipient's disease into account. Forty adults underwent liver transplantation using left (n = 10; mean weight, 481 +/- 83 g) or right lobes (n = 30; mean weight, 845 +/- 182 g). We recorded graft survival, Child-Turcotte-Pugh score, and occurrence of small-for-size syndrome (poor bile production, prolonged postoperative prothrombin time, and cholestasis without ischemia markers). Small grafts were defined as GRWR of < or =0.85%. Large grafts were defined as GRWR greater than 0.85%. Six patients died within 6 months of transplantation (early patient survival rate, 85%); two patients died late of tumor recurrence. Among transplant recipients with normal liver function or Child's class A, there was no significant difference with the use of small (n = 6) or large (n = 9) grafts (graft survival rates, 83% v 88%, respectively; P =.65). Among patients with Child's class B or C, graft survival rates were 74% in recipients of large grafts (n = 19) and 33% in recipients of small grafts (n = 6; P =.023). Five of 6 patients with Child's class B or C who received small grafts developed small-for-size syndrome; 2 patients died (1 patient after retransplantation) and 3 patients survived (2 patients after retransplantation). Graft function and survival are influenced not only by graft size, but also by pretransplantation disease severity. GRWR as low as 0.6% can be used safely in patients without cirrhosis or in patients with Child's class A. Transplant recipients with Child's class B or C require a GRWR greater than 0.85% to avoid small-for-size syndrome and related complications.

Orthotopic liver transplantation for Wilson's disease: a single-center experience.

BACKGROUND: Wilson's disease is an inherited disorder of copper metabolism characterized by reduced biliary copper excretion, which results in copper accumulation in tissues with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with Wilson's disease who present with fulminant liver failure and for patients unresponsive to medical therapy. The aim of this study is to review our experience with OLT for patients with Wilson's disease. METHODS: Between 1988 and 2000, 21 OLTs were performed in 17 patients with Wilson's disease. Patient demographics, pre-OLT laboratory data, operative data, and early and late postoperative complications were reviewed retrospectively. One-year patient and graft survival was calculated. RESULTS: Eleven patients had fulminant Wilson's disease; in six patients the presentation was chronic. Mean patient age at presentation was 28 years (range 4-51 years); mean follow-up was 5.27 years (range 0.4-11.4 years). Neurologic features of Wilson's disease were not prominent preoperatively and did not develop post-OLT except in one patient who developed acute neuropsychiatric illness and seizure. Renal failure, present in 45% of patients with fulminant Wilson's disease, resolved post-OLT with supportive care. One-year patient and graft survivals were 87.5% and 62.5%, respectively. Fifteen survivors have remained well with normal liver function and no disease recurrence. CONCLUSION: Liver transplantation for hepatic complications of Wilson's disease cures and corrects the underlying metabolic defect and leads to long-term survival in patients who present with either acute or chronic liver disease. Acute renal failure develops frequently in patients with fulminant Wilsonian hepatitis and typically resolves postoperatively.

Preoperative and intraoperative predictors of postoperative morbidity, poor graft function, and early rejection in 190 patients undergoing liver transplantation.

HYPOTHESIS: Preoperative and intraoperative variables predict in part adverse outcome after liver transplantation. DESIGN: Prospective, blinded, cohort study. SETTING: Tertiary care hospital. SUBJECTS: A total of 190 adult patients undergoing primary liver transplantation. MAIN OUTCOME MEASURE: Adverse outcome was prospectively defined as either in-hospital death or prolonged postoperative hospitalization (>14 days) associated with morbidity. Potential preoperative and intraoperative risk factors were collected. Associations were tested by univariate analysis followed by multivariate analysis in which preoperative factors were entered before intraoperative factors. RESULTS: Adverse outcome occurred in 44.7% of patients. Incidences of other complications were as follows: in-hospital mortality (8.4%), primary graft nonfunction (4.2%), poor early graft function (1.1%), and early rejection (31.2%). Univariate predictors of adverse outcome were United Network for Organ Sharing status (P =.003), Child-Turcotte-Pugh score (P =.02), POSSUM physiological score (P =.002), recipient age (P =.01), preoperative serum high-density lipoprotein cholesterol level (P =.03), preoperative serum creatinine level (P =.002), preoperative serum total IgG level (P =.004), duration in hospital preoperatively (P =.03), operative duration (P<.001), allogeneic erythrocyte transfusions (P<.001), total intraoperative fluids (P =.002), and use of inotropic agents (P =.01). In the final multivariate model, predictors of adverse outcome were United Network for Organ Sharing status (P =.03), recipient age (P =.002), and total intraoperative fluids (P =.04). Most patients who died or had a prolonged hospitalization exhibited dysfunction of more than 1 organ system, including pulmonary, renal, and infectious complications. CONCLUSIONS: Adverse outcome occurs frequently after liver transplantation, usually involves multiple organ systems, and is predicted in part by several preoperative and intraoperative factors.

One hundred nine living donor liver transplants in adults and children: a single-center experience.

OBJECTIVE: To summarize the evolution of a living donor liver transplant program and the authors' experience with 109 cases. SUMMARY BACKGROUND DATA: The authors' institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. METHODS: Donors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. RESULTS: After ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. CONCLUSION: Living donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.

Recurrence of hepatitis C after liver transplantation is associated with increased systemic IL-10 levels.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost universal occurrence. T-cell derived cytokines have an important role in the development of liver damage associated with chronic hepatitis C, their post-transplant levels, however, have not been correlated with histologic recurrence of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2 receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in 27 patients undergoing transplantation for hepatitis C related end-stage liver disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal amplification assay. Diagnosis of recurrent hepatitis was based on 1-year protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS: Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA levels rose over time in all patients regardless of histologic recurrence. TNF-alpha, and IL-4 levels, although elevated, did not show specific patterns over time or in correlation with recurrence. Similarly, the early elevation followed by a gradual decrease over the first year in the amount of soluble IL-2 receptor was not related to histologic recurrence. We observed a significant increase in circulating IL-10 levels over the first year in patients with biopsy-proven recurrence, while patients with no signs of histologic recurrence displayed increased, but steady levels. CONCLUSIONS: These results suggest that while these cytokines are associated with post-transplant recurrence of hepatitis C, their production may be altered by additional factors.

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function.

The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF) and steroids is a new option for initial immunosuppression in patients undergoing liver transplantation (LT) with impaired renal function. We evaluated the efficacy and safety of daclizumab in preventing rejection in 25 patients with impaired kidney function undergoing LT. Patients with serum creatinine (Cr) levels greater than 2 mg/dL immediately before LT were administered initial immunosuppression with daclizumab, 1 mg/kg, in addition to MMF, 2 g/d, and methylprednisolone. Tacrolimus was added after kidney function improved (when Cr levels improved by >25% of initial value). Daclizumab-treated patients were compared retrospectively with 2 other groups of patients who underwent LT with kidney impairment (Cr > 2 mg/dL): 56 patients were administered OKT3 induction, and 48 patients were administered low-dose tacrolimus. The incidence of rejection and infection (bacterial, fungal, and viral), need for preoperative and postoperative dialysis, Cr level immediately post-LT and at 3 months, and graft and patient survival were analyzed. There was no difference among the groups in 3-month Cr levels or the incidence of rejection or fungal or viral infection. The daclizumab group had fewer bacterial infections (n = 13) than the tacrolimus group (n = 28) and significantly fewer than the OKT3 group (n = 58; P =.006). Only 1 patient (4%) in the daclizumab group required dialysis post-LT versus 13 patients in each of the other groups (OKT3, 23.21%; P <.05; tacrolimus, 27%). In the daclizumab group, 2-year patient and graft survival rates were statistically significant compared with the low-dose tacrolimus group (89% and 81% v 73% and 69%, respectively; P =.06). There were no side effects related to daclizumab use, and all patients tolerated the drug well. In patients with impaired renal function before LT, daclizumab-based initial immunosuppression can be used safely to reduce the risk for infection and need for dialysis post-LT, with improved long-term graft and patient survival.

Safety and risk of using pediatric donor livers in adult liver transplantation.

Pediatric donor (PD) livers have been allocated to adult transplant recipients in certain situations despite size discrepancies. We compared data on adults (age > or = 19 years) who underwent primary liver transplantation using livers from either PDs (age < 13 years; n = 70) or adult donors (ADs; age > or = 19 years; n = 1,051). We also investigated the risk factors and effect of prolonged cholestasis on survival in the PD group. In an attempt to determine the minimal graft volume requirement, we divided the PD group into 2 subgroups based on the ratio of donor liver weight (DLW) to estimated recipient liver weight (ERLW) at 2 different cutoff values: less than 0.4 (n = 5) versus 0.4 or greater (n = 56) and less than 0.5 (n = 21) versus 0.5 or greater (n = 40). The incidence of hepatic artery thrombosis (HAT) was significantly greater in the PD group (12.9%) compared with the AD group (3.8%; P =.0003). Multivariate analysis showed that preoperative prothrombin time of 16 seconds or greater (relative risk, 3.206; P =.0115) and absence of FK506 use as a primary immunosuppressant (relative risk, 4.477; P =.0078) were independent risk factors affecting 1-year graft survival in the PD group. In the PD group, transplant recipients who developed cholestasis (total bilirubin level > or = 5 mg/dL on postoperative day 7) had longer warm (WITs) and cold ischemic times (CITs). Transplant recipients with a DLW/ERLW less than 0.4 had a trend toward a greater incidence of HAT (40%; P <.06), septicemia (60%), and decreased 1- and 5-year graft survival rates (40% and 20%; P =.08 and.07 v DLW/ERLW of 0.4 or greater, respectively). In conclusion, the use of PD livers for adult recipients was associated with a greater risk for developing HAT. The outcome of small-for-size grafts is more likely to be adversely affected by longer WITs and CITs. The safe limit of graft volume appeared to be a DLW/ERLW of 0. 4 or greater.

Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a western experience.

BACKGROUND: We reviewed our experience in patients with hepatocellular carcinoma (HCC) and chronic hepatitis to determine if differences exist in preoperative status and postoperative survival between those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. METHODS: We reviewed the records of 240 consecutive patients with HCC who underwent hepatic resection or liver transplantation at Mount Sinai Hospital between February 1990 and February 1998. Patients who tested negative for hepatitis B antigen and hepatitis C antibody (74 patients) as well as those who tested positive for both (2 patients) were excluded. Age as well as preoperative platelet count, prothrombin time (PT), albumin, and total bilirubin were measured in all patients. The presence of encephalopathy or ascites also was noted. Explanted livers and resection specimens were examined for size, number, and differentiation of tumors as well as the presence of vascular invasion and cirrhosis in the surrounding parenchyma. RESULTS: One hundred twenty-one patients with HCC tested positive for HCV, and 43 tested positive for HBV. A significantly higher proportion of patients with HCV required transplant for the treatment of their HCC when compared to those with HBV. In the resection group, patients with HCV were significantly older that those with HBV. They also had significantly lower mean preoperative platelet counts and albumin levels and higher mean PT and total bilirubin levels. Resected patients with HCV had significantly less-differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to those with HBV. There was no statistical difference in the multicentricity and size of tumors between the two groups. The 5-year disease-free survival was significantly higher for HBV patients treated with resection when compared to those with HCV (49% vs. 7%, P = .0480). Patients with HCC and HCV had significantly longer 5-year disease-free survival with transplant when compared to resection (48% vs. 7%, P = .0001). Transplanted patients with HBV and HCC had preoperative status, pathological findings, and survival similar to those of patients with HCV. CONCLUSIONS: Based on preoperative liver function and tumor location, a much higher proportion of HCC patients with HBV were candidates for resection. Significant differences in preoperative status, tumor characteristics and disease-free survival exist between HCC patients with chronic HBV and HCV infection who have not yet reached end-stage liver disease. Serious consideration should be given to transplanting resectable HCC with concomitant HCV, especially in cases with small tumors.

Liver transplantation for autoimmune hepatitis.

Publications about liver transplantation (LTX) for autoimmune hepatitis (AIH) have started to emerge, but many issues remain unresolved. We reviewed data on 32 patients transplanted for AIH to determine how pretransplantation and posttransplantation characteristics correlate with recipient outcome, including disease recurrence. Recipients were 37+/- 14 years old; 30 of 32 were women. Most had chronic disease (8 +/- 6 years); 25% had fulminant failure. The majority had ascites (91%), jaundice (88%), elevated prothrombin time (18 +/- 3 seconds), and hypoalbuminemia (2.7 +/- 0.6 g/dL). All had hypergammaglobulinemia (3.0 +/- 1.0 g/dL) and autoantibodies (72% antinuclear, 74% smooth muscle). Only one was HLA A1-B8-DR3 positive. Other autoimmune disorders affected 25% of patients; half improved after transplantation. Actuarial survival was 81% at 1 and 2 years posttransplantation. There was a high frequency of rejection (75% of recipients had 1.7 +/- 0.8 episodes), and 39% of rejections required OKT3. Among 24 recipients with long-term follow-up (27 +/- 14 months), histologically proven recurrent AIH occurred in 25%, 15 +/- 2 months posttransplantation; half (3 patients) required retransplantation 11 +/- 3 months after diagnosis. After retransplantation 2 of 3 patients had re-recurrence within 3 months; 1 received a third LTx. Recurrence occurred in 6 of 18 patients transplanted for chronic disease vs. 0 of 6 transplanted as fulminants (P = not significant [NS]). Patients with and without recurrence had similar rejection profiles. In summary, results of LTx for AIH are excellent. However, AIH patients have a high frequency of rejection and often require OKT3. Furthermore, severe recurrent AIH sometimes develops, particularly in chronic versus fulminant AIH patients and in those already retransplanted for recurrence. Multicenter studies could elucidate the best posttransplantation immunosuppressive regimens for AIH patients.

Hepatitis C after liver transplantation.

Hepatitis C is the most common cause of end-stage liver disease leading to liver transplant. The disease can recur after transplant, resulting in clinical hepatitis in up to 75% of patients and severe disease in approximately 7%. Treatment of rejection with steroid boluses and treatment of steroid-resistant rejection with OKT3 have both been shown to increase the incidence of recurrent hepatitis C. The use of OKT3 for steroid-resistant rejection is reportedly associated with more severe recurrence. The calcineurin inhibitors tacrolimus and cyclosporine have not been conclusively associated with different rates or severity of recurrence. Viral levels rise 10- to 15-fold after transplant and appear to be associated with the use of immunosuppression. Studies suggest that high viral levels, either pretransplant or early after transplant, may be associated with severe recurrent disease. Although the role of genotype is still unclear, genotype 1b is known to be associated with a poorer prognosis in nontransplanted patients and a lesser response to treatment than other genotypes. Furthermore, some reports suggest that after transplant, recurrent disease may progress more rapidly in patients with genotype 1. Treatment options after recurrence remain poor. Neither interferon nor ribavirin alone provides any true benefit. Combination therapy appears to have a better short-term outcome but may be poorly tolerated, and long-term benefits are unknown. Prophylaxis with combination therapy may be a better option but requires further study. Finally, retransplantation for recurrent hepatitis C is complicated not by rapid recurrence of disease in the new allograft but by high perioperative mortality that may be predicted by the presence of renal failure or sepsis preretransplant.

Non-adherence in pediatric liver transplant recipients--an assessment of risk factors and natural history.

Despite the fact that non-adherence to medical therapy is one of the major causes of late morbidity and mortality in pediatric liver transplant recipients, little is known of the risk factors involved in this behavior. Three cases of fatal non-adherence are reported. Factors associated with non-adherence were investigated by performing a retrospective chart review of a panel of 27 variables in an age-matched cohort of 15 pediatric liver transplant recipients. The most striking differences between the severely non-adherent group and the age-matched cohort included history of substance abuse, child abuse (physical or sexual), not having two parents at home, having received public assistance, having been diagnosed with a psychiatric disorder, and history of school dropout. In addition it appeared that a pretransplant diagnosis of autoimmune hepatitis was associated with more significant medical sequelae related to non-adherence. These findings are preliminary owing to the retrospective design of this study, but could be used as a starting point for a prospective study of this important phenomenon.

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.

When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.

Retransplantation for late liver graft failure: predictors of mortality.

As patient survival after orthotopic liver transplantation (OLT) improves, late complications, including late graft failure, more commonly occur and retransplantation (re-OLT) is required more often. Survival after re-OLT is poorer than after primary OLT, and given the organ shortage, it is essential that we optimize our use of scarce donor livers. We sought to identify variables that predict poor outcome after late re-OLT. Among adults who underwent OLT between September 1989 and October 1997, we identified transplant recipients who survived greater than 6 months (n = 964) and analyzed those who required late re-OLT (>/=6 months after primary OLT). We recorded the indication for the initial OLT and interval from OLT to re-OLT. We also analyzed data collected at the time of re-OLT, including age, sex, indications for primary OLT and re-OLT, United Network for Organ Sharing status, preoperative laboratory values (white blood cells, platelets, hemoglobin, albumin, bilirubin, creatinine, and prothrombin time), Child-Pugh-Turcotte score, number of rejection episodes before re-OLT, and interval between OLT and re-OLT. In addition, we analyzed surgical factors (including procedure performed and use of packed red blood cells, fresh frozen plasma, and platelets), postoperative immunosuppression, and donor factors (age, ischemic time). Forty-eight patients (5%) underwent late re-OLT at a median of 557 days (range, 195 to 2,559 days) post-OLT. Survival rates after re-OLT at 90 days, 1 year, and 5 years were 71%, 60%, and 42%, respectively. Patients surviving 90 days or greater after re-OLT had an 85% chance of surviving to 1 year. Sepsis was the leading cause of death (15 of 25 deaths; 60%). Recipient age older than 50 years (P =.04), preoperative creatinine level greater than 2 mg/dL (P =.004), and use of intraoperative blood products (packed red blood cells, P =.001; fresh frozen plasma, P =.002; platelets, P =.004) had significant impacts on survival. Late re-OLT was associated with increased mortality. Careful patient selection, with particular attention to recipient age and renal function, may help improve results and optimize our use of scarce donor livers.

Central nervous system complications in liver transplant recipients--incidence, timing, and long-term follow-up.

BACKGROUND: Neurological impairment is a major source of morbidity and mortality following orthotopic liver transplantation (OLT). We reviewed our experience with neurologic complications among our first 463 consecutive adult OLT recipients. METHODS: Between September 1988 and October 1993, 463 adult patients underwent OLT. Data on incidence, time of onset, and outcome of central nervous system (CNS) complications was obtained from patient charts, including autopsy results when available. CNS complications were classified by clinical presentation and by etiology. RESULTS: 93 patients (20.1%) had CNS complications following OLT. Encephalopathy (11.8%) and seizure (8.2%) were the leading complications. The incidence of immunosuppressive drug-related complications was 5.6%; coma, 1.7%; cerebral hemorrhage, 1.5%; central pontine myelinolysis (CPM), 1.2%; stroke, 0.6%; and primary CNS lymphoma, 0.2%. Most CNS events (80%) were encountered in the first month after OLT. In the majority of cases, encephalopathy (70%) and seizure (50%) presented in the first 2 wk. Although most CNS infections occurred early, 2 patients developed tuberculous meningitis more than 1 yr post-OLT. In 12 patients, death was directly related to CNS complications (2.6%). CONCLUSIONS: Most CNS complications occur early following OLT but may be seen even after 1 yr. Patients may survive serious neurologic events, such as cerebral hemorrhage, CPM, and meningitis.

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.

OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.