A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C.

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS.

Pediatric liver transplantation for acute liver failure at a single center: a 10-yr experience.

Children transplanted for ALF urgently require an optimal graft and have lower post-transplant survival compared with children transplanted for chronic liver disease. Over 10 yr, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type ABOI, XL (GRWR > 5%), DDSLT, LDLT and WLT were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. Twelve of 33 received ABOI, five XL grafts, 18 DDSLT, and three LDLT. Waiting time pretransplant was 2.1 days. One- and three-yr patient survival in the ALF group was 93.4% and 88.9%, and graft survivals were 86.4% and 77.7%. Median follow-up was 1452 days. ABOI one- and three yr patient and graft survival in the ALF was 91.6% and 78.6%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group or the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, XL grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival comparable to patients with non-acute disease.

Successful outcome after early combined liver and en bloc-kidney transplant in an infant with primary hyperoxaluria type 1: a case report.

PH1 is a metabolic disorder characterized by urolithiasis and the accumulation of oxalate crystals in the kidneys and other organs. Although patients often first present with renal failure, PH1 results from a deficiency of the hepatic peroxisomal enzyme AGT. Ultimately only liver transplantation will cure the underlying metabolic defect. Herein, we report the case of a three-month-old male infant diagnosed with PH and treated using a combined liver and en bloc-kidney transplant from a single donor. At the time of transplant, the patient was 11 months old and weighed 7.9 kg. He received a full size liver graft and en bloc kidneys from a two-yr-old donor. At 36 months post-transplant, the patient is steadily growing with normal renal and hepatic function. This is one of the first reports of successful liver and en bloc-kidney transplantation with abdominal compartment expansion by PTFE for the infantile form of PH1 in a high risk child before one yr of age. Prompt diagnosis and early referral to a specialized center for liver and kidney replacement offer the best chance for survival for infants with this otherwise fatal disease.

The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation.

BACKGROUND: Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. MATERIALS AND METHODS: The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.

Experience with ulcerated, bleeding autologous dialysis fistulas.

PURPOSE: The incidence of ulcerated, bleeding, autologous, hemodialysis fistulas has been felt to be increasing in recent years. This review was undertaken to examine our experience with patients who presented with episodes of spontaneous bleeding in the presence of an ulcerated lesion over their autologous dialysis accesses. METHODS: A database of hemodialysis access procedures was reviewed for individuals with spontaneous bleeding from ulcerations. Twenty-four patients were identified with 28 ulcerating lesions over a ten-year period from 2001 to 2011. Each had at least a single episode of spontaneous bleeding. Treatment methods were reviewed including five techniques of surgical intervention. RESULTS: Two of 24 patients expired from major hemorrhagic events before obtaining surgical consultation (8.3%). Twenty-one patients (87.5%) underwent 28 surgical procedures for correction of the ulcers. One patient (4.1%) with simultaneous ulcers healed under antibiotic therapy during close observation in hospital. Simple suturing of the ulcer was found to be inconsistent in effectively maintaining hemostasis. Surgical excision of the ulcer with primary closure, vein patching of the fistula, or end-end anastomosis were equally effective in definitively correcting the problem. CONCLUSIONS: The ulcerated autologous dialysis fistula is a life-threatening lesion and requires prompt surgical intervention to reduce mortality. The frequency of this problem appears to be increasing. Simple suturing of the ulcers was not consistently effective in remedying the problem and should be utilized as a temporizing measure until surgical correction can be undertaken. Fistulas can be uniformly salvaged with surgical intervention enabling uninterrupted dialysis treatments.

Surgical correction of nephrogenic ascites in a renal transplant recipient.

The unusual development of massive ascites, 3 years after renal transplant, caused by undefined, innate renal allograft pathology is described. Challenges of surgical correction of this problem, allowing for salvage of the allograft, are reviewed.

A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation.

The Model for End-Stage Liver Disease (MELD) score is now the criteria for allocation in liver transplantation for patients with chronic disease. Although the score has been effective in the prediction of mortality in patients awaiting liver transplantation, its abilities to predict posttransplantation outcome need study. The aim of this study is to compare outcome in the first 2 years after liver transplantation according to the pretransplantation MELD score. The study includes 669 consecutive patients who underwent primary liver transplantation between December 1993 and October 1999 in a single transplant center. Patients who died of malignancy were excluded from the series. Pretransplantation MELD score was calculated using the United Network for Organ Sharing formula. Patients were stratified according to MELD score less than 15, 15 to 24, and 25 and higher. Posttransplantation survival at 3, 6, 12, 18, and 24 months was significantly lower in the groups with a higher MELD score. The difference was significant for hepatitis C and noncholestatic liver diseases, but not cholestatic diseases. In patients with a MELD score between 15 and 24, survival was significantly greater with cholestatic diseases and lower in patients with hepatitis C. In our study, pretransplantation MELD score correlates with survival in the first 2 years after transplantation. There is a survival advantage for patients with cholestatic diseases compared with those with hepatitis C. These findings suggest the need to readjust MELD score-based allocation decisions to consider patient outcome.

Syndromic incidence of ovarian carcinoma after liver transplantation, with special reference to anteceding breast cancer.

Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United States. Previous studies had found a decreased incidence of female gynecological malignancies after liver transplantation. In order to estimate the incidence of ovarian carcinoma after liver transplantation, we evaluated 1708 consecutive liver transplant recipients from 1984 to 2001. Of them, 770 (43%) were female. Routine follow-ups were performed at 1, 2, 5, and 10 years after transplantation. There were two cases of ovarian carcinoma. Both occurred in recipients with a previous history of breast cancer. Based on these data, we conclude that the incidence of ovarian cancer is 1:385 among all female liver transplant recipients, and 1:6.5 among those with a history of pretransplant breast cancer. We recommend that regular check-ups should be undertaken, especially in the population at highest risk.

Pretransplant MELD score as a predictor of outcome after liver transplantation for chronic hepatitis C.

The Model of End-Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post-transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty-seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15-24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12 months were significantly lower in the higher MELD score groups, as was patient survival at 24 months (p-values, 0.01-0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1 year post-transplant was significantly lower with higher MELD scores (p = 0.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post-transplant graft injury in these patients should be explored.

Unusually high incidence of positive HTLV I/II results among young female organ donors in the peripartum period.

HTLV I and II are unusual retroviruses associated with multiple neurologic and hematologic disorders. We observed an unusually high incidence of HTLV I-II seropositivity among young and middle-aged female organ donors, especially among those in the peripartum period. Ethical issues may arise when informing the families as well as when deciding whether to use organs from these donors. Further confirmatory tests may be difficult to obtain because of time and economic constraints associated with organ procurement.

De novo tumors after liver transplantation: a single-institution experience.

The aims of this analysis are to characterize the incidence and types of malignancies and tumor-specific mortality in our institution. Retransplantation, rejection episodes, and OKT3 use were evaluated. Our single-institution prospective database of 1,570 liver transplantations in 1,421 patients was analyzed. Data were statistically analyzed regarding sex, age at transplantation, time from transplantation to diagnosis of tumor, tumor type, and follow-up time. One hundred twenty-five patients (8.8%) developed de novo tumors; 69 patients were men, 56 patients were women. Seventeen patients received more than one allograft. De novo tumors were as follows: skin, 41; lymphomas, 35; lung, 11; colon, 6; anal, 2; rectal, 1; breast, 7; thyroid, 3; oropharyngeal squamous cell, 3; metastatic without primary tumor identified, 4; renal cell, 3; Kaposi's sarcoma, 1; angiosarcoma, 1; uterine, 1; ovarian, 1; pituitary, 1; pancreatic, 2; cholangiocarcinoma, 1; and esophageal, 1. These tumors developed in a statistically significant chronological sequence. Lung cancers and lymphomas showed shorter mean survival times, as well as greater mortality. OKT3 use and rejection did not show significance in tumor development. De novo tumors post-liver transplantation affected our population in a distribution similar to that of the general non-transplantation population. Intense short courses of immunosuppression for rejection were not as important as chronic immunosuppression in the development of tumors. The risk for development was not enough to preclude transplantation. We found that tumors developed in chronological fashion. Therefore, directed surveillance, patient education, and early detection may facilitate earlier treatment.

Correlation between intraoperative blood flows and hepatic artery strictures in liver transplantation.

Hepatic artery strictures (HASs) may be a source of morbidity and mortality in liver transplant recipients. This study evaluated the potential correlation between intraoperative arterial and venous blood flows measured after implantation of the liver allograft and the occurrence of postoperative HASs requiring repair. Prospectively collected data from 1,038 patients with complete data sets who underwent initial orthotopic liver transplantations between December 1984 and December 1999 were used. Electromagnetic flow measurements were routinely obtained in these cases. Hepatic artery and portal vein patency were reassessed routinely according to our protocol in the first postoperative day by Doppler ultrasound. When considered hemodynamically significant, strictures were corrected. There was a 6.2% incidence (n = 64) of hepatic artery stenosis in our transplant population. When considered as a whole, the hepatic artery stenosis group had lower intraoperative flow volumes than transplant recipients who did not develop strictures (mean flows, 452 v 518 mL/min, respectively; P =.025). The hepatic artery stenosis group also had lower intraoperative portal vein flows compared with the group without hepatic artery stenosis (1.80 v 2.11 L/min, respectively; P =.0043). Strictures were less frequent among transplant recipients with cryptogenic cirrhosis. We did not observe differences among the groups for retransplantation or patient and graft survival. In our series, there was a 6.2% incidence of postoperative HASs. We observed a significant association between intraoperative hepatic artery and portal vein flows and postoperative HASs.

Incidence and recurrence of autoimmune/alloimmune hepatitis in liver transplant recipients.

We prospectively collected data on 1,429 liver transplant recipients between December 1984 and December 1998. Fifty-five patients (3.8%; 10 men, 45 women; median age, 44.5 +/- 13 [SD] years) with autoimmune hepatitis (AIH) underwent orthotopic liver transplantation (OLT). Transplant recipients with AIH were younger, more likely to be women, and had a greater likelihood of rejection in the first 3, 6, and 12 months. There was no difference in patient survival or graft survival. There were 11 biopsy-proven recurrences (1 man, 10 women) of AIH after OLT. Almost half the episodes occurred within the first year after OLT. No patient required re-OLT because of recurrent disease. AIH has an incidence of 4% and a recurrence rate of 20% in OLT. Transplant recipients are more likely to be young women and have an increased incidence of acute cellular rejection (ACR) during the first post-OLT year. Recurrence should be suspected in those with abnormal liver function test results in the absence of ACR, especially during the first year after OLT. We cannot establish with certainty whether the observed process represents recurrence of the original autoimmune disease, an alloimmune phenomenon, or allograft dysfunction mimicking AIH.

Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population.

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.

Treatment of unresectable hepatoblastoma with liver transplantation in the pediatric population.

The purpose of our study was to evaluate the outcome of children who underwent liver transplantation as treatment for unresectable hepatoblastoma. We prospectively collected data on 311 consecutive liver transplants performed at Children's Medical Center of Dallas between October 1984 and November 2000. There were nine recipients (five boys, four girls) with a diagnosis of unresectable hepatoblastoma. Postoperative survival of those currently alive ranged from 6 months to 16 years (mean 6.4 years, median 7.7 years). All recipients received preoperative chemotherapy: 67% received postoperative chemotherapy. Mean AFP level prior to transplantation was 1 448000 ng/mL. Mean age at diagnosis was 0.81 years. Mean age at transplantation was 1.87 years. Only two patients experienced acute cellular rejection in the postoperative period. There was a total of three deaths and one recurrence. The only instance in which AFP levels did not decrease to low or undetectable levels post-transplantation was in the patient with recurrent tumor. Liver transplantation has an established role in the treatment of hepatoblastoma. It accounted for 3% of pediatric liver transplants, and provided the only opportunity for survival in otherwise incurable patients. Early diagnosis and treatment were found to be associated with better results. Response to chemotherapy may be an important factor influencing survival. Rising AFP levels after transplantation are associated with recurrence.

Thrombendvenectomy for organized portal vein thrombosis at the time of liver transplantation.

OBJECTIVE: To determine the efficacy of portal thrombendvenectomy in cases of portal vein thrombosis at the time of orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Portal vein thrombosis (PVT) has been reported to have an incidence of 2% to 39% in end-stage liver disease. Multiple techniques have been suggested to treat this finding. Several reports have suggested suboptimal results after liver transplantation in recipients with PVT. METHODS: The authors prospectively collected data on 1,546 patients who underwent an initial orthotopic liver transplant at the authors' institution between December 1984 and October 1999. There were 820 male patients and 726 female patients. All recipients received either cyclosporine or tacrolimus immunosuppression. Intraoperative flows of the portal vein and hepatic artery were routinely measured. Duplex sonography was routinely performed on the first postoperative day and routinely 1, 2, 5, and 10 years after transplantation. Eighty-five patients underwent thrombendvenectomy for organized thrombus partially or completely occluding the portal vein. Postoperative treatment included low-molecular-weight dextran for 48 hours and daily aspirin for 3 months. There were 53 male patients and 32 female patients. The PVT group was compared with a control group consisting of transplant recipients without PVT. RESULTS: When compared with the control group, PVT patients were older at the time of transplantation and had a higher incidence of liver disease secondary to cryptogenic cirrhosis and Laennec's cirrhosis. There were no significant differences among both groups for 1-, 3-, and 6-year patient and graft survival rates. CONCLUSIONS: Thrombendvenectomy provides a rapid resolution of an otherwise complex problem. It is the authors' procedure of choice in cases of organized PVT at the time of transplantation. Operative time and length of stay in the intensive care unit are not prolonged, and patient and graft survival rates are not compromised.