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Background: Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatoblastoma (HBL). Although post-transplant outcomes have improved in the contemporary era, the impact of donor graft type on survival remains unclear., Methods: Using the United Network for Organ Sharing database (02/2002-06/2021), demographics, clinical characteristics, and patient and graft survival were analyzed in children (<18 years) who underwent LT for HBL according to donor graft type. The Kaplan-Meier method, log-rank tests, and Cox regression modeling were used to evaluate the effect of whole, partial, and split deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) on patient and graft survival., Results: A total of 590 pediatric HBL LT recipients (344 whole graft DDLT; 62 partial graft DDLT; 139 split graft DDLT; 45 LDLT) were included. During 2012-2021 the proportion of LDLTs for HBL decreased to about 5% compared with about 11% during 2002-2011. No significant differences were identified by donor graft type in either patient survival (log-rank test, p = .45) or graft survival (log-rank test, p = .69). The results remained similar during the 2002-2011 era, while during the 2012-2021 era, split graft DDLT was associated with decreased graft loss risk versus whole graft DDLT (hazard ratio: 0.48, 95% confidence interval: 0.23-0.99, p = .046) without any other significant between-group differences., Conclusions: Utilizing non-whole liver grafts can increase access to LT in children with unresectable HBL while ensuring favorable outcomes. LDLT is underutilized in children with HBL in the United States, and efforts to explore LDLT options should be undertaken., (© 2023 Wiley Periodicals LLC.)

Background: Hepatic undifferentiated embryonal sarcoma (HUES) is the third most common primary hepatic malignancy in children. If unresectable, liver transplantation (LT) is the only curative option. Historically, HUES LT outcomes were not favorable; however, modern-era data are lacking. We aimed to describe LT outcomes in children with HUES and compared with LT outcomes in children transplanted for hepatoblastoma (HBL) and non-malignancy indications., Methods: Children 18 years or younger with HUES who underwent LT from 1987 to 2021 were identified from the Scientific Registry of Transplant Recipients database. Graft and patient survival were studied in HUES and LT recipients with HBL and non-malignancy indications using Kaplan-Meier analysis. Cox regression was used to compare patient and graft survival among groups, controlling for confounders., Results: Twenty-one children with HUES underwent LT during the study period with a median age at LT of 10 years (IQR: 8-12 years). One and five-year patient survival for HUES recipients was not significantly different from that of recipients with HBL (p = .3) or non-malignancy diagnoses (p = .6). There were no deaths due to HUES recurrence. In multivariable Cox regression, HUES did not increase risk of either patient or graft loss as compared to HBL (HR 2.36, p = .2) or non-malignancy indications (HR 0.74, p = .7)., Conclusion: LT outcomes are more favorable in patients with HUES than historically described, and similar to LT outcomes of patients with HBL and non-malignancy indications. Transplant should be considered for HUES patients with unresectable localized tumors., (© 2023 Wiley Periodicals LLC.)

Introduction: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU., Methods: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU., Results: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P ​< ​0.001) and low tPA TEG LY30 (OR 3.7, P ​= ​0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p ​< ​0.001) was observed patients who had these risk factors for pICU., Conclusion: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT., Competing Interests: Declaration of competing interest Hunter Moore has patent issued with the tPA TEG that is licensed through the University of Colorado. This intellectual property is owned the University of Colorado. Haemonetics provided reagents at a discounted price, but was not involved with data analysis, interpretation, or any contribution to this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Background: Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT., Methods: The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance., Results: Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01)., Conclusions: ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed., (© 2022 Wiley Periodicals LLC.)

Background: Immediate extubation (IE) following pediatric liver transplantation is being increasingly performed. The aim of this study was to characterize the rate of IE at our institution and identify recipient factors predictive of IE., Methods: All pediatric liver transplants performed at our institution between January 1, 2015 and December 31, 2020 were reviewed. Retransplants and multi-organ transplants were excluded. IE was defined as extubation in the operating room following transplant. Backward stepwise logistic regression at a p-value threshold of .05 was performed to identify variables associated with IE., Results: IE was achieved in 58 (72%) of the 81 pediatric liver transplants. The IE cohort had significantly shorter ICU length of stay and overall hospital length of stay, though IE was not an independent predictor of posttransplant length of stay. Age <2 years, preoperative mechanical ventilation, and total intraoperative epinephrine and dopamine infusion requirements were significant, independent risk factors against IE. This multivariable model was highly predictive of IE (area under the curve = 0.89)., Conclusions: We describe the highest rate of IE postpediatric liver transplantation that has been reported to date and identified significant risk factors against successful IE., (© 2022 Wiley Periodicals LLC.)

Introduction: Kasai hepatoportoenterostomy is the standard of care for children with biliary atresia, but a majority of patients progress to end-stage liver disease and require a salvage liver transplant. Given the high failure rates of the hepatoportoenterostomy operation, some have advocated for primary liver transplantation as a superior treatment approach. The aim of this study was to compare outcomes of pediatric candidates with biliary atresia listed for primary vs. salvage liver transplantation., Methods: The SRTR/OPTN database was retrospectively reviewed for all children with biliary atresia listed for liver transplant between March 2002 and February 2021. Candidates were categorized as primary liver transplant if they had not undergone previous abdominal surgery prior to listing and salvage liver transplant if they had. Salvage transplants were further categorized as early failure if listed within the first year of life or late failure if listed at an older age., Results: 3438 children with biliary atresia were listed for transplant during the study period, with 15% of them listed for a primary transplant, 17% for salvage transplant after early failure, and 67% after late failure. Recipients of salvage liver transplant with late failure had lower bilirubin levels and were less critically ill as demonstrated by MELD/PELD scores and hospitalization status. Correspondingly, these recipients had higher waiting list and graft survival, though this did not remain statistically significant after adjustment in multivariable models. There were no differences in waiting list, recipient, or graft survival with primary vs. salvage liver transplant after early failure., Conclusion: Kasai hepatoportoenterostomy should remain the standard of care in biliary atresia as it may delay need for transplant beyond the first year of life in a subset of recipients and does not jeopardize subsequent transplant outcomes, even with early failure., Levels of Evidence: Retrospective cohort study (Level III)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pediatric living donor liver transplantation (LDLT) remains infrequently performed in the United States and localized to a few centers. This study aimed to compare pediatric waiting list and posttransplant outcomes by LDLT center volume., Methods: The Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network database was retrospectively reviewed for all pediatric (age <18 y) liver transplant candidates listed between January 1, 2009, and December 31, 2019. The average annual number of LDLT, deceased donor partial liver transplant (DDPLT), and overall (ie, LDLT + DDPLT + whole liver transplants) pediatric liver transplants performed by each transplant center during the study period was calculated., Results: Of 88 transplant centers, only 44 (50%) performed at least 1 pediatric LDLT during the study period. LDLT, DDPLT, and overall transplant center volume were all positively correlated. LDLT center volume was protective against waiting list dropout after adjusting for confounding variables (adjusted hazard ratio, 0.92; 95% confidence interval, 0.86-0.97; P  = 0.004), whereas DDPLT and overall center volume were not ( P  > 0.05); however, DDPLT center volume was significantly protective against both recipient death and graft loss, whereas overall volume was only protective against graft loss and LDLT volume was not protective for either., Conclusions: High-volume pediatric LDLT center can improve waiting list survival, whereas DDPLT and overall volume are associated with posttransplant survival. Expertise in all types of pediatric liver transplant options is important to optimize outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population., Methods: The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age <40 y, single vasopressor or less, transaminases no >3 times the normal limit, and body mass index ≤ 28 kg/m2., Results: Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from <1% to 3% in the same time. While 28% of DO donors met splitting criteria, only 3% of those meeting splitting criteria were used as a split graft. Both pediatric and adult recipients of DO donor livers achieved excellent patient and graft survival., Conclusions: DO donors are underutilized in pediatric liver transplantation. Increased splitting of DO donor livers could significantly decrease, if not eliminate, the pediatric liver waiting list., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Amidst the coronavirus (COVID-19) pandemic, the American Society for Transplant Surgeons has recommended that only urgent liver transplant with deceased donors should occur. However, young pediatric candidates rely on living donors for lifesaving transplant. We present a case of non-directed left lateral lobe living liver donor transplant for a 7-month-old child with biliary atresia experiencing repeated life-threatening episodes of sepsis and cholangitis from infected bile lakes. Using careful preoperative planning among the entire multidisciplinary team, paying meticulous attention to infection control pre- and post-operatively, and taking advantage of robust telehealth technology both in and out of the hospital, a successful transplant was achieved. Amidst the COVID pandemic, non-directed liver transplantation can be safely achieved for pediatric recipients., (© 2020 Wiley Periodicals LLC.)

Aim: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions., Methods: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin., Results: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006)., Conclusion: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.

Bacterial, viral, and fungal infections can be devastating in a postoperative liver transplant recipient on multidrug immunosuppressive therapy. Various atypical (nontuberculous mycobacteria [NTM]) mycobacterial infections have been reported in the solid organ transplant population, but to our knowledge, no cases of Mycobacterium mucogenicum infections have been reported. Here, we report a case of a patient with end-stage liver disease secondary to primary biliary cirrhosis, model for end-stage liver disease score of 29, who underwent deceased-donor orthotopic liver transplantation, with her postoperative course complicated by multiple pleural effusions and peritonitis. Despite numerous courses of antibiotics, her condition did not improve. Acid-fast bacilli cultures grew M. mucogenicum, which was then treated with appropriate antimicrobical therapy. M. mucogenicum, a rapidly growing NTM that can be present in water contamination, should be recognized as a potential source of infection, especially in the immunocompromised population., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this case report we describe the blood metabolic profile ("metabolomics") by nuclear magnetic resonance (NMR) spectroscopy and principle component analysis (PCA) from a patient who underwent two consecutive liver transplantations. The first graft from a living-related donor failed and was followed by a second successful transplant from a deceased donor. Using quantitative high-resolution H-NMR spectroscopy, 48 endogenous metabolites were analyzed in whole blood samples at baseline and different time points after each transplantation. From 48 analyzed metabolites, six metabolites were identified by PCA as metabolic markers consistent with a non-functional liver after first transplantation. Importantly, this distinctive metabolic profile was present as early as two hours after first transplant surgery when no other variable or conventional laboratory tests indicated poor graft function. This article reports the potential usefulness of quantitative H-NMR based metabolomics to diagnose early graft dysfunction in liver transplantation.

Liver transplantation is now an acceptable treatment for small hepatocellular carcinomas in the setting of cirrhosis. Larger tumors in cirrhotic livers and unresectable tumors in noncirrhotic livers (including fibrolamellar hepatocellular carcinomas) may also be indications for transplantation. With the limited number of cadaver grafts available, living donor liver transplant is becoming an option for some of these patients. We describe a method of reconstruction of the recipient inferior vena cava with deceased donor graft in right lobe living donation for fibrolamellar hepatocellular carcinoma.

Primary sclerosing cholangitis (PSC) is the fourth leading diagnosis in liver transplant recipients in the United States. The disease is known to recur in 15% to 30% of liver transplant recipients. We set out to investigate how different immunosuppression regimens affected natural history of PSC after liver transplantation at our center. We reviewed records of all patients who underwent a liver transplantation at our institution in between 1988 and 2000 and had a diagnosis of PSC at the time of liver transplantation. Primary sclerosing cholangitis recurred in 15 of 71 patients (21.1%) who had complete records and survived more than 30 days after liver transplantation. Although recurrence of primary sclerosing cholangitis was most often seen (but not statistically significantly so) in patients who received maintenance corticosteroids, the time to recurrence was not significantly different between those who were treated with maintenance, those who were not successfully weaned, and those who successfully weaned off corticosteroids within 3 months after liver transplantation. Orthoclone (OKT3) therapy (Ortho-Biotech, Inc., Raritan, NJ) was associated with a higher risk of primary sclerosing cholangitis recurrence (29% versus 10%, P <.05). Recurrence was not influenced by immunosuppression with either cyclosporine or tacrolimus. Coexistent inflammatory bowel disease was a cause of failure to wean off corticosteroids, was associated with a shorter time to recurrence of sclerosing cholangitis, and was responsible for significant comorbidity (colon cancer in 7.3%). Primary sclerosing cholangitis recurrence is commonly seen after liver transplantation. More immunosuppression seems to be detrimental to the outcome of our patients with sclerosing cholangitis: use of OKT3 was associated with a greater incidence of recurrence. Length of corticosteroid use did not affect timing or risk of recurrence, and because it has been proven that early corticosteroid withdrawal after liver transplantation is beneficial, we continue to recommend this practice.

Background: Bile duct injury is a major complication of laparoscopic cholecystectomy. The purpose of this study was to evaluate our management strategy and outcomes for the treatment of such injuries., Methods: We studied 54 consecutive patients who had de novo bile duct injury (n = 20) or prior biliary injury repair (n = 34) associated with laparoscopic cholecystectomy. All patients were managed using a multidisciplinary approach., Results: Definitive operation, almost always Roux-en-Y hepaticojejunostomy, was required in 85% of patients. We inserted external percutaneous biliary catheters in 98% of cases prior to surgery. There were no operative deaths, and the 30-day complication rate was 20%. Eight patients (15%) were managed nonoperatively. Overall, 96% of patients had no long-term, objectively definable biliary sequelae., Conclusions: Treatment of bile duct injury associated with laparoscopic cholecystectomy is optimally done using a multidisciplinary approach. Surgical reconstruction is required in most cases and can be safely accomplished with minimal morbidity and excellent long-term outcomes.

Since its approval as an immunosuppressive agent in renal transplantation, sirolimus (RAPA) recently has been used in the primary immunosuppression regimen at several liver transplant centers. One of the major side effects of RAPA is hypercholesterolemia, which is reported in up to 44% of patients. We describe our experience in 57 primary liver transplant recipients treated with RAPA and either cyclosporine A (CSA) or tacrolimus (TAC). We report the incidence and severity of hypercholesterolemia using a prednisone-free immunosuppressive regimen. Between January 2000 and September 2000, a total of 57 patients underwent transplantation at the University of Colorado Health Sciences Center (Denver, CO) with RAPA and either CSA or TAC. The initial 10 patients who underwent transplantation under this protocol were not administered corticosteroids, and the subsequent 47 patients were administered only 3 doses of methylprednisolone days 0, 1, and 2 postoperatively (1, 0.5, and 0.5 g, respectively). Total fasting cholesterol, high-density cholesterol, low-density cholesterol, and triglyceride levels were measured at monthly intervals. Mean serum cholesterol level was significantly greater in CSA patients (200 mg/dL) compared with TAC patients (158 mg/dL; P =.0003). Serum triglyceride levels were more than 2-fold greater with CSA (292 mg/dL) compared with TAC (134 mg/dL; P =.002). Hypercholesterolemia (cholesterol > 240 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (8 of 27 patients; 30%) compared with TAC-treated patients (2 of 30 patients; 6%; P <.05). Hypertriglyceridemia (serum triglyceride > 300 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (9 of 27 patients; 33%) compared with TAC-treated patients (1 of 30 patients; 3%; P <.05). We conclude that (1) concomitant use of TAC with RAPA reduces the prevalence and severity of posttransplantation dyslipidemia, and (2) these findings have important implications in the prevention of complications of hypercholesterolemia in liver transplant recipients.

Combined liver-pancreas transplantation is a relatively uncommon procedure. We report successful combined liver-pancreas transplantation in a patient with primary sclerosing cholangitis and insulin-dependent diabetes mellitus and review the literature on this topic.

Background: Living donor liver transplantation has gained wide acceptance as an alternative for children with end-stage liver disease. The standard left lateral segment used in this operation does not provide adequate parenchymal mass to broaden its application to larger children or adults., Methods: We report two cases of adult to adult living donor liver transplantation using a right hepatic lobe in patients with chronic liver disease., Results: Both recipients experienced excellent initial graft function and have normal liver function 4 and 9 months postoperatively. Both donors are alive and well and returned to normal life 4 weeks postoperatively., Conclusions: Our initial experience suggests that this technique is a safe and reliable option for adults with chronic end-stage liver disease. A conservative application of this procedure in the adult population could significantly reduce the mortality on the adult waiting list.

Background: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications., Methods: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia., Results: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months)., Conclusions: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.

Background: Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study., Methods: Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression., Results: The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation., Conclusions: The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

Fibrosing cholestatic hepatitis in a specific histologic manifestation of hepatitis B virus infection consisting of periportal fibrosis, hepatocyte ballooning, cholestasis, a relatively scant inflammatory infiltrate, and marked overexpression of hepatitis B viral antigens in hepatocytes. Until recently, fibrosing cholestatic hepatitis had been reported only in recipients of liver allografts. In this report, we present two patient in whom this lesion developed following renal transplantation. Both patients had previous liver biopsies showing relatively mild histologic changes. In one patient, the lesion developed early after retransplantation, during the period of maximal immunosuppression. However, in the second patient this lesion developed after withdrawal of immunosuppression. In both cases, death occurred within a few months because of progressive liver disease. Since this lesion can develop in "relatively healthy" hepatitis B carriers following transplantation of organs other than liver, these patients should have careful monitoring of their liver disease. Moreover, since the disease may progress despite withdrawal of immunosuppression, these patients would clearly benefit from the development of more effective therapies for posttransplant hepatitis B.

An end-to-end choledochocholedochostomy (CD) over a T tube or a Roux-en-Y choledochojejunostomy (CDJ) have been the standard method of biliary reconstruction following orthotopic liver transplantation (OLTx). The objective of this study was to assess whether or not use of the T tube leads to increased biliary tract complications. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. OLTx was performed in 161 patients over an 18-month period. Fifty-one patients were excluded from the study leaving a total of 110 patients for evaluation. Fifty-nine had their bile duct reconstructed over a T tube (CD T tube, group I) while the remaining 51 patients underwent bile duct reconstruction without a T tube (CD, group II). No difference was noted between groups I and II in their survival rate, rate of conversion to Roux-en-Y CDJ, or biliary complication rates. Our results indicate that CD (i.e., without a T tube) is both a safe and effective technique to reconstruct the biliary tract following hepatic transplantation. Routine use of a T tube with a CD anastomosis is unnecessary in most liver transplant patients. In addition, the omission of a T tube has reduced the number of radiological procedures performed at our center.

Background: Total vascular exclusion (TVE) of the liver has been used to increase the safety of hepatectomy and the feasibility of difficult resections. Until recently, however, concern about the detrimental effect of warm ischemia has limited the use of this technique to patients with normal liver parenchyma., Objective: To compare surgical outcomes of 12 patients with abnormal livers (group 1) with outcomes of 48 patients with normal parenchyma (group 2), based on the hypothesis that uncontrolled bleeding may be more detrimental than planned hepatic ischemia., Design and Setting: Retrospective analysis of 60 consecutive patients undergoing liver resection under TVE in a university medical center., Patients: All 10 patients with cirrhosis had albumin levels of 30 g/L or higher and normal prothrombin times preoperatively; none had ascites. Two patients with cholestasis (one with cholangiocarcinoma and one with hepatocellular carcinoma) are included in group 1., Intervention: All 12 group 1 patients and 44 of 48 group 2 patients underwent total or extended lobectomy, with TVE induced by clamping the hilum and the vena cava above and below the liver during parenchyma division., Main Outcome Measures: Hospital survival and selected surgical and laboratory parameters., Results: Operative times, ischemic times, and blood loss (1975 +/- 1601 vs 1255 +/- 1291 mL) (P = .10) were comparable in both groups. Sixty-day operative mortality was zero in both groups. There was an increased rate of complications in group 1 (44% vs 17% [P = 0.06]). Transient abnormal liver function was observed in both groups. However, significant delay in restoration of normal function was observed in group 1 with respect to bilirubin levels and prothrombin time., Conclusions: Patients with cirrhosis can undergo successful resection using TVE. This conclusion must be limited to cirrhotic patients with good liver function. The trend toward increased blood loss may reflect greater difficulties in establishing hemostasis after reperfusion in group 1. While this group appears to have a higher risk for hepatic insufficiency, successful outcomes were achieved in all cases. Prospective study will be required to define the parameters for use of TVE in cirrhosis.

Liver allografts from HBcAb(+), IgM(-), HBsAg(-) donors can transmit HBV to uninfected recipients. We currently no longer accept these livers for transplantation while continuing to accept the kidneys. The purpose of this study is to determine the risk of donor-transmitted HBV infections from HBcAb(+), HBIgM(-), HBsAg(-) organ donors and determine if the risk of donor-transmitted HBV infections and their severity is dependent on the organ being transplanted. This study consists of a retrospective review of the posttransplant course of recipients of HBcAb(+), HBIgM(-), HBsAg(-) donors accepted at UCSF from 6/85 to 12/93. Transmitted HBV infection was defined as one in which the recipient changed from HBsAg(-) prior to transplantation to HBsAg(+) posttransplant, with no other source. There were 25 of 1190 donors who were HBcAb(+), HBIgM(-), HBsAg(-); 1/42 kidney, 3/6 liver, and 0/7 heart HBsAg(-) transplant recipients of organs from these donors became HBsAg(+) after transplantation. This difference in infection rate (liver vs. kidney and heart) is statistically significant. The clinical course of the liver recipients was also more severe. All of the patients who became infected were HBsAb(-) and HBcAb(-) prior to transplant. We conclude that (1) HBV can be transmitted from HBcAb(+), HBIgM(-), HBsAg(-) organ donors, (2) the rate of transmission is highest and severity of infection is worst in the liver recipients; and (3) we will continue to transplant kidneys from these donors, preferably into immunized recipients.

Advances in endoscopic surgical techniques and laser technology have expanded the role of thoracoscopy. We report a thoracoscopic resection of a benign pulmonary lesion. A 44-year-old man underwent a successful Nd:YAG laser-assisted thoracoscopic resection of a peripheral lung hamartoma. The patient's postoperative course was uncomplicated. Thoracotomy with its attendant morbidity was avoided. Continued success with thoracoscopic resection will have a significant impact on the management of select patients with peripheral, solitary pulmonary nodules.

Background: Patients with a history of malignant disease and new pulmonary lesions often are considered for resection to establish a diagnosis and, with certain histologic subtypes, to improve survival. Standard operative therapy consists of thoracotomy and wedge resection of the lesion. Early and late postoperative morbidity is substantial and related primarily to the thoracotomy incision., Methods: Advances in endoscopic surgical techniques and laser technology allowed for successful thoracoscopic resection of an isolated pulmonary metastasis in a 59-year-old man with a history of a T3N0M0 renal cell carcinoma., Results: The margins of the specimen were free of tumor. The postoperative course was uncomplicated, and the patient was discharged on the fourth postoperative day. The morbidity associated with a standard thoracotomy was avoided, and an adequate resection was obtained., Conclusion: Continued success with thoracoscopic resection may have a significant impact on the management of selected patients with a history of malignant disease and new pulmonary lesions.