Search

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR)., Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery., Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers., Exposures: cDCD livers were recovered by either NRP or SRR., Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival., Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts., Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies., (Copyright © 2023 American Association for the Study of Liver Diseases.)

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients., (Copyright © 2022 American Association for the Study of Liver Diseases.)

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons., Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC., Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers., Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001)., Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background and Aims: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013)., Approach and Results: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001)., Conclusions: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation., (© 2020 by the American Association for the Study of Liver Diseases.)

Objective: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT)., Background: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study., Methods: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression., Results: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67)., Conclusions: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5-7.1 years). The median time from transplant to first infection was 3 years (range: 0.8-5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23-valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC)., Summary Background Data: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited., Methods: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013)., Results: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044)., Conclusions: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

Aplastic anemia (AA) has been observed in nearly a third of patients undergoing liver transplantation (LT) for non-A-E fulminant hepatic failure (FHF). Few of these patients have been successfully managed with sequential LT and bone marrow transplantation (BMT). No causative agent has been identified for the FHF or AA in these reported cases. At our center, two patients, aged 15 years and 7 years, respectively, underwent sequential living-related LT and living-unrelated BMT. These patients are 10/9 years and 5/4 years post-LT/BMT. Human parvovirus B19 (HPV-B19) was established as the causative agent for FHF in both these patients by polymerase chain reaction. This report presents the first two cases associating HPV-B19 with FHF and AA who underwent sequential LT and BMT with excellent outcomes., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Liver transplantation (LTx) is a life-saving treatment of end-stage liver disease. Cardiac complications including heart failure (HF) are among the leading causes of death after LTx., The Aim: The aim is to identify clinical and echocardiographic predictors of developing HF after LTx., Methods: Patients who underwent LTx at the University of Nebraska Medical Center (UNMC) between January 2001 and January 2009 and had echocardiographic study before and within 6 months after transplantation were identified. Patients with coronary artery disease (>70% lesion) were excluded. HF after LTx was defined by clinical signs, symptoms, radiographic evidence of pulmonary congestion, and echocardiographic evidence of left ventricular dysfunction (left ventricle ejection fraction <50%)., Results: Among 107 patients (presented as mean age [SD], 55 [10] years; male, 70%) who met the inclusion criteria, 26 (24%) patients developed HF after LTx. The pre-LTx left ventricle ejection fraction did not differ between the HF (69 [7]) and the control groups (69 [7] vs. 67 [6], P=0.30). However, pre-LTx elevation of early mitral inflow velocity/mitral annular velocity (P=0.02), increased left atrial volume index (P=0.05), and lower mean arterial pressure (P=0.03) were predictors of HF after LTx in multivariate analysis. Early mitral inflow velocity/mitral annular velocity greater than 10 and left atrial volume index 40 mL/m2 or more were associated with a 3.4-fold (confidence interval, 1.2-9.4; P=0.017) and 2.9-fold (confidence interval, 1.1-7.5; P=0.03) increase in risk of development of HF after LTx, respectively., Conclusions: This study suggests that elevated markers of diastolic dysfunction during pre-LTx echocardiographic evaluation are associated with an excess risk of HF and may predict post-LTx survival.

Background: More data on the risk factors and outcomes after Staphylococcus aureus infections in liver transplantation are needed., Methods: Liver recipients with S. aureus infections (cases) were retrospectively identified and compared to gender-, age-, and transplant type-matched (1:2) non-S. aureus-infected controls. Risk factors associated with S. aureus infections were identified by conditional logistic regression analysis., Results: We evaluated 51 patients (median age 52 years). First S. aureus infections developed at a median time of 29 days after transplantation, with 52.94% of them in the first month; 88.24% were nosocomial, 41.18% were polymicrobial, and 47.06% were caused by methicillin-resistant S. aureus (MRSA). Surgical site infections represented 58.82% and bacteremia 23.53%. By univariate analysis, patients with S. aureus infections were intubated more frequently (odds ratio [OR] 26.92, 95% confidence interval [CI] 3.23-3,504.15, p = 0.0006), had a central line (OR 11.69, 95% CI 1.42-95.9, p = 0.02), or recent surgery (OR 26.92, 95% CI 3.23-3,504.15, p = 0.0006) compared with controls. By multivariate analysis, subjects who underwent surgery within 2 weeks prior to infection had a 26.9 times higher risk of developing S. aureus infection (95% CI 3.23-3,504.15, p = 0.0006); these results were adjusted for matched criteria. S. aureus infections did not affect graft or patient survival, but the study was not powered for such outcomes., Conclusion: Only recent surgical procedure was found to be a significant independent risk factor for S. aureus infections after liver transplantation.

Adult-to-adult living donor liver transplantation (AA-LDLT) has better outcomes when a graft weight to recipient weight ratio (GW/RW) > 0.8 is selected. A smaller GW/RW may result in small-for-size syndrome (SFSS). Portal inflow modulation seems to effectively prevent SFSS. Donor right hepatectomy is associated with greater morbidity and mortality than left hepatectomy. In an attempt to shift the risk away from the donor, we postulated that left lobe grafts with a GW/RW < 0.8 could be safely used with the construction of a hemiportocaval shunt (HPCS). We combined data from 2 centers and selected suitable left lobe living donor/recipient pairs. Since January 2005, 21 patients underwent AA-LDLT with left lobe grafts. Sixteen patients underwent the creation of an HPCS between the right portal vein and the inferior vena cava. The portocaval gradient (portal pressure - central venous pressure) was measured before the unclamping of the shunt and 10 minutes after unclamping. The median actual graft weight was 413 g (range = 350-670 g), and the median GW/RW was 0.67 (range = 0.5-1.0). The portocaval gradient was reduced from a median of 18 to 5 mmHg. Patient survival and graft survival at 1 year were 87% and 81%, respectively. SFSS developed in 1 patient, who required retransplantation. Two patients died at 3 and 10 months from a bile leak and fungal sepsis, respectively. The median recipient bilirubin level and INR were 1.7 mg/dL and 1.1, respectively, at 4 weeks post-transplant. One donor had a bile leak (cut surface). This is the first US series of small left lobe AA-LDLT demonstrating that the transplantation of small grafts with modulation of the portal inflow by the creation of an HPCS may prevent the development of SFSS while at the same time providing adequate liver volume. As it matures, this technique has the potential for widespread application and could positively effect donor safety, the donor pool, and waiting list times., (2010 AASLD.)

Background: This study examines the impact of donor liver macrovesicular steatosis on recurrence of hepatitis C virus (HCV) disease after liver transplantation., Methods: Between 1998 and 2004, 113 patients underwent liver transplantation for HCV-related cirrhosis. Time to histologic recurrence (fibrosis score >or=2) was the primary endpoint of the study. Recurrence was graded according to the system of Ludwig and Batts. A Cox's proportional hazard regression model was used to analyse the association between donor liver steatosis and HCV recurrence., Results: Recurrence-free survival for patients who received steatotic grafts was 82% and 47% at 1 and 4 years, respectively, and 81% and 52% for patients who received a non-steatotic liver. Donor macrovesicular steatosis (5-45%) was found to have no impact on HCV recurrence (P=0.47). Donor age (P=0.02) and cold ischaemia time (P=0.01) were found to increase the relative risk of HCV recurrence. The estimated risk of HCV recurrence increased by 23% for every 10-year increase in donor age. Similarly the risk of recurrence increased by 13% for every 1-h increase in cold ischaemia time., Conclusion: Mild-moderate donor liver macrovesicular steatosis has no impact on HCV recurrence after liver transplantation for HCV-related cirrhosis. Cold ischaemia time and donor age increased the likelihood of HCV recurrence.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.

Infants with short bowel syndrome (SBS) and associated liver failure are often referred for combined liver/intestinal transplantation. We speculated that in some young children, nutritional autonomy would be possible with restoration of normal liver function. Features we believed to predict nutritional autonomy include history of at least 50% enteral tolerance, age less than 2 yr, and no underlying intestinal disease. This report documents our experience with liver transplantation alone in children with liver failure associated with SBS. Twenty-three children with SBS and end-stage liver disease, considered to have good prognostic features for eventual full enteral adaptation, underwent isolated liver transplantation. Median age was 11 months (range, 6.5 to 48 months). Median pretransplant weight was 7.4 kg (range, 5.2 to 15 kg). All had growth retardation and advanced liver disease. Bowel length ranged from 25 to 100 cm. Twenty-three children underwent 28 isolated liver transplants. There were 14 whole livers and 14 partial grafts (five living donors). Seventeen patients are alive at a median follow-up of 57 months (range, 6 to 121 months). Actuarial patient and graft survival rates at 1 yr are 82% and 75% and at 5 yr are 72% and 60%, respectively. Four deaths resulted from sepsis, all within 4 months of transplantation, and 1 death resulted from progressive liver failure. Two allografts developed chronic rejection; both children were successfully retransplanted with isolated livers. Of 17 surviving patients, three require supplemental intravenous support; the remaining 14 have achieved enteral autonomy, at a median of 3 months (range, 1 to 72 months) after transplantation. Linear growth is maintained and, in many, catch-up growth is evident. Median change in z score for height is 0.57 (range, -4.47 to 2.68), and median change in z score for weight is 0.42 (range, -1.65 to 3.05). In conclusion, Isolated liver transplantation in children with liver failure as a result of SBS, who have favorable prognostic features for full enteral adaptation, is feasible with satisfactory long-term survival., (Copyright 2006 AASLD)

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver transplantation and to perform a multivariate analysis for possible risk factors. In this retrospective study, 91 patients transplanted for PSC or AIH, without prior colectomy, were included. Sixty patients were transplanted for PSC, 31 for AIH. IBD activity before and after OLT and other possible risk factors were analysed in a multivariate model. Forty-nine patients (54%) had IBD before OLT. Forty patients (44%) had active IBD after transplantation: recurrence in 32 and de novo in 8. Cumulative risk for IBD after OLT was 15, 39 and 54% after 1, 5 and 10 years, respectively. In 59% of patients with IBD prior to OLT the disease was more active after transplantation. Risk factors for recurrent disease were: symptoms at time of OLT, short interval of IBD before OLT and use of tacrolimus. 5-aminosalicylates were protective. A cytomegalovirus positive donor/negative recipient combination increased the risk for de novo IBD.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The application of living donor liver transplantation (LDLT) in the management of unresectable HB may add new therapeutic opportunities. We evaluated the outcomes of patients who underwent liver transplantation for treatment of unresectable HB in the period between August 1985 and June 2003. Ten children had a diagnosis of unresectable HB. Mean age at transplantation was 5.8 yr. Eight patients were transplanted with deceased donor grafts. Two patients underwent LDLT. Pre-transplant chemotherapy was used in 90% of cases. Post-transplant survival ranges from 3.7 to 18.6 yr. Three patients died of recurrent disease at 4, 14 and 38 months. The two LDLT recipients were able to get pre-transplant chemotherapy with a rapid decision towards transplantation; both are alive and well at 5.5 and 11 yr post-transplant. Our experience supports the role of LDLT and deceased donor liver transplantation in the management of unresectable HB when waiting times can be detrimental to the patient's survival.

The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3(+) lymphocytes and 50% of his CD19(+) lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3(+)CD4(-)CD8(-) with T-cell receptor gammadelta heterodimers and CD3(+)CD4(-)CD8(+) with CD8alphaalpha homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs.

The most significant development in liver transplantation in the USA over the past year was the full implementation of the MELD- and PELD-based allocation policy in March 2002, which shifted emphasis from waiting time within broad medical urgency status to prioritization by risk of waiting list death. The implementation of this system has led to a decrease in pretransplant mortality without increasing post-transplant mortality, despite a higher severity of illness at the time of transplant. The trend over the last few years of rapidly increasing numbers of adult living donor liver transplants was reversed in 2002 by a decline of more than 30% in the number of these procedures. In 2002, a greater percentage of women received livers from living donors (43%) than deceased donors (34%), possibly because of size considerations. From 1993 to 2001, the waiting list increased more than sixfold, from 2902 patients to 18,047 patients. For the first time since 1993, the waiting list size decreased in 2002, dropping 6% to 16,974 candidates. The percentage of temporarily inactive liver candidates also increased from 2001, thus the net decrease in the active waiting list for 2002 was 12%. This may reflect a trend toward less pre-emptive listing practices under MELD. Intestine transplantation remains a low-volume procedure limited to a few transplant centers and is still accompanied by significant pre- and post-transplantation risks. As this procedure matures, its application may increase to include recipients at an earlier stage of their disease with better likelihood of success.

A 26-year-old woman presented with acute Budd-Chiari syndrome 18 weeks into a pregnancy. She was found to be heterozygous for the G20210A prothrombin gene mutation. She was treated with portacaval shunt placement and successfully completed the pregnancy, with a healthy baby delivered at 31 weeks' gestation. She developed progressive liver failure after delivery of the child, likely associated with clotting of the shunt, which occurred in the face of full anticoagulation. The patient subsequently underwent a technically complicated orthotopic liver transplantation, but died 10 months after transplantation. This case illustrates the challenges involved in the treatment of Budd-Chiari syndrome, in addition to difficulties balancing the health of a mother and an unborn child. It is the only case of surgical treatment of Budd-Chiari syndrome during pregnancy reported in the literature.

Objective: To evaluate experience with isolated orthotopic liver transplantation in children with liver failure associated with short bowel syndrome (SBS)., Summary Background Data: Infants who have liver failure as a result of SBS are frequently referred for consideration for combined liver and small bowel transplantation. In a few patients the liver disease develops despite a seemingly adequate bowel, which if given time and appropriate management has the potential for full enteral adaptation. There is a limited literature suggesting the utility of OLT without replacement of the native bowel. The advantages over combined liver and small bowel transplantation are clear: organ availability is greater, liver-reduction techniques are well established, lower immunosuppression is required, and there is greater experience in the care of children after orthotopic liver transplantation., Methods: Eleven infants, considered to have a good prospect of eventual gut adaptation to full enteral nutrition if it were not for their advanced liver disease, underwent isolated orthotopic liver transplantation. Age range was 6.5 to 17.7 months. All patients had been dependent on parenteral feeding but had also shown significant enteral tolerance at some time before listing for transplantation. Advanced liver disease was apparent both clinically and on histologic examination. All were jaundiced and had low albumin levels, and most had coagulopathy. As a group the infants had growth retardation. Estimated remaining length of small bowel beyond the ligament of Treitz was in the range of 25 to more than 100 cm. Six infants retained their ileocecal valve., Results: Thirteen liver transplants were performed in the 11 patients. A combination of whole livers (n = 6) and reduced-size grafts, of which three were from living-related donors, were used. Biliary anastomosis was duct-to-duct in eight instances and involved a short Roux limb in the others. Eight patients are alive with follow-up of 15 to 66 months. Three deaths have occurred after transplantation as a result of sepsis. Of eight surviving patients, only two continue to receive intravenous support and in both there is increasing enteral tolerance. Since transplantation, all surviving children have shown adequate growth with maintenance of pretransplant centiles., Conclusions: In selected infants with liver failure secondary to short bowel syndrome in whom complete enteral autonomy is anticipated, isolated liver transplantation can offer long-term survival.

The most common application of small bowel transplantation is for the patient with parenteral nutrition-induced liver failure. In this setting, the small intestine is transplanted simultaneously with the liver. We identified three technical problems that we believe contributed to complications in our first eight patients. First, pancreaticoduodenectomy was challenging in the infant donor. Second, the bowel graft was prone to volvulus around the skeletonized donor portal vein. Third, in the pediatric recipient, use of the donor bowel for Roux-en-Y biliary reconstruction was associated with biliary leaks in the early postoperative period. Our surgical technique of liver/small bowel (L/SB) transplantation has evolved since our early experience in 1990. Modifications in the L/SB operation, reported briefly in 1996 and 1997, have led to easier graft preparation and have reduced the incidence of technical complications.

Background: Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation. Extracorporeal liver perfusion (ECLP) has been proposed as a method of "bridging" such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure., Methods: Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver., Findings: Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully "bridged" to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 micromol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 micromol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit., Interpretation: These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

We report four children with advanced liver disease awaiting liver transplantation who developed moderately severe hypercalcemia (range: 1.65-2.40 mmol/L) while receiving total parenteral nutrition. Hypercalcemia had been unresponsive to cessation of calcium intake and therapy with loop diuretics and calcitonin. One or two intravenous doses of disodium pamidronate (35-50 mg/m2) resulted in normalization of plasma calcium concentration within 2-4 d in all four children. Pamidronate may be useful for children with hypercalcemia associated with liver disease.

Objective: To review a single center's 10-year experience with liver transplantation (LTx) for the biliary atresia-polysplenia syndrome (BA-PS) and to define surgical and clinical guidelines for its management., Summary Background Data: BA is the most common indication for pediatric liver transplantation (LTx) and is associated with PS in 12% of cases. Only a few studies of LTx for BA-PS have been reported, and the optimal management of BA-PS patients undergoing LTx has yet to be determined., Methods: From July 1985 to September 1995, 166 liver transplants were performed in 130 patients with BA and were included in the study. The malformations most commonly associated with BA-PS, surgical techniques used to overcome these anomalies, and surgical pitfalls that could have contributed to the outcome were characterized. Actuarial 10-year patient and graft survival for patients undergoing LTx for BA-PS were calculated and compared to those with isolated BA., Results: Ten patients (7.8%) with BA had associated PS. An additional patient with PS without BA was included in the study. The diagnosis of PS was unknown before the transplantation in 72% of cases. Thirteen liver transplants were performed in these 11 patients. Modifications of the usual surgical technique were used to overcome the complex anatomy encountered. There was no association between the type of anomaly and the outcome, nor were there any significant differences in patient survival (72% vs. 73.5%, p = 0.79) or graft survival (56.4% vs. 54.6%, p = 0.54)., Conclusions: The association of BA with various anomalies should be considered a spectrum that may vary widely from patient to patient. The finding of two or more of these malformations in a patient awaiting transplantation should lead the surgeon to look systematically for other associated anomalies. With some special surgical considerations, the outcome in BA-PS patients should not differ from those with isolated BA.

Children who have undergone liver transplantation may develop chronic diarrhea for a number of reasons. Three children who underwent liver transplantation for liver failure, all of whom had had previous biliary and intestinal surgeries and whose postoperative course was marked by signs and symptoms of intestinal malabsorption including chronic diarrhea, are described. Duodenal aspirates showed a panoply of bacterial species, and duodenal histology featured villus atrophy in two: one associated with luminal gram-positive cocci and another with acute and chronic duodenitis. Oral antibiotics cleared the symptoms. Small bowel bacterial overgrowth may need to be considered in children with chronic diarrhea after liver transplantation, especially when previous intestinal surgery has taken place. Long-term antibiotic therapy may be required to effectively eradicate the offending organisms to suppress symptoms.

Objective: This study was undertaken to review the incidence and causes of death in children who have survived long-term (more than 1 year) after liver transplantation (LT)., Summary Background Data: No studies of the causes of late mortality in pediatric LT recipients are currently available in the literature., Methods: The study group consists of 212 pediatric patients who survived more than 1 year after LT. Twenty-three of these patients subsequently died (mean follow-up = 5.3 yr). Hospital records, office charts, and autopsy records were reviewed retrospectively to identify the causes of death. The patients who died were further evaluated by age, gender, length of survival, primary diagnosis, immunosuppression, and retransplantation., Results: The most common cause of death was graft failure, followed closely by infection. In patients dying from graft failure, eight of the nine patients underwent retransplantation and no child survived more than three liver transplants. Overwhelming infections occurred suddenly in eight children who had been previously healthy. Noncompliance was the third most common cause of death, primarily in older children. One child died from a posttransplant lymphoproliferative disorder (PTLD). Actuarial survival at 10 years is 83.7% (based on 100% survival at 1 year). There was no difference in survival based on primary disease. Retransplantation was far more prevalent in the nonsurvivors (47.8%) compared with survivors (13.7%) (p < 0.05). There were no significant differences in survival based on age, gender, or immunosuppression., Conclusions: Late mortality in children continues to be directly related to complications of LT and immunosuppression, even after the first year of transplantation. This is in contrast to adult liver transplant recipients, where approximately 50% of late deaths were related to LT and the remainder were because of unrelated illnesses.

Background: Tissue endothelial adhesion molecule expression is increased during acute liver allograft rejection. Soluble forms exist, but their correlation to rejection and their clinical value have not been determined., Methods: We studied endothelial adhesion molecule tissue expression and soluble levels in blood and bile and correlated these to the clinical course of 11 adult patients followed for 30 consecutive days after liver transplantation., Results: Three biopsies showing acute rejection demonstrated increased intercellular adhesion molecule (ICAM)-1 but not endothelial leukocyte adhesion molecule-1 expression on hepatic endothelial cells during rejection. Vascular cell adhesion molecule (VCAM)-1 staining was focally increased in two of three specimens. Levels of soluble ICAM-1 or soluble VCAM-1 by ELISA did not distinguish acute rejection from nonrejection conditions., Conclusion: We confirmed that endothelial ICAM-1 expression is more intense in rejecting allografts and is more sensitive than changes in VCAM-1 or endothelial leukocyte adhesion molecule-1. However, soluble adhesion molecule determination was not useful in the accurate detection of acute rejection.

Vancomycin-resistant Enterococcus faecium (VREF) has become a significant nosocomial pathogen for immunosuppressed patients. During a 5-month period in 1993, 8 cases of invasive infection with VREF (7 with bacteremia) were identified in liver transplant recipients, half of whom were adults. Epidemiology and microbiology studies were designed to identify the source and to determine the risk factors for this infection. Overall mortality was 50% (3 adults and 1 child). Mortality in bacteremic patients was 57%. A case-control study showed that cases were more likely to have been treated with a third-generation cephalosporin or vancomycin and to have undergone more than four biliary tract procedures. Environmental surveillance cultures yielded only one VREF isolate from a rectal temperature probe, but this device was used in only 2 of the cases. Cultures from all surgery and radiology suites were negative. All VREF isolates were genotyped by contour-clamped homogenous electric field electrophoresis of chromosomal DNA restriction fragments. These studies showed that a single clone was responsible for the outbreak, although other clones could be detected in the hospital. After implementing strict contact isolation on the liver transplant unit, only 1 additional patient with VREF was identified during this outbreak. In conclusion, it was found that antibiotic use and biliary tract manipulation were risk factors for developing invasive infections with VREF after liver transplantation. Optimal treatment is still unclear but most likely includes a combination of two or more antibiotics. Prompt institution of infection control measures can preclude rapid spread of this nosocomial pathogen.

Background: Auxiliary orthotopic liver transplantation (AOLT) was investigated as a bridge to native liver recovery in patients with fulminant hepatic failure (FHF)., Methods: In the last 5 years seven patients with FHF were treated with AOLT at our institution. Five patients underwent resection of the native left lobe and orthotopic replacement with a donor left lobe (n = 3) or left lateral segment (n = 2). Two patients underwent left trisegmentectomy and whole liver auxiliary grafting. Conventional immunosuppression was used in all patients., Results: One patient had poor initial graft function and required retransplantation. Native liver function returned to normal in the six other patients. Immunosuppression was gradually tapered and completely discontinued in three patients, allowing for atrophy of the allograft. The allograft was removed in the other four patients. Despite evidence of native liver regeneration, two patients with aplastic anemia died after allograft removal. Four patients are alive at a mean follow-up of 3.5 years., Conclusions: AOLT is technically feasible, rapidly restores liver function, and should be considered an important alternative to standard orthotopic liver transplantation (OLT) in the treatment of FHF. AOLT has the advantage that patients transplanted for FHF are not committed to lifelong immunosuppression with its attendant risks.

Objective: The indications for and the results of portosystemic shunts done in the authors' institution since initiation of a liver transplant program 10 years ago were reviewed., Summary Background Data: With the widespread availability of liver transplantation as definitive treatment of chronic liver disease, the role of shunts in the overall management of variceal bleeding needs to be redefined., Methods: Seventy-one variceal bleeders with cirrhosis who received a shunt (82% distal splenorenal shunts) because of sclerotherapy failure or because endoscopic treatment was not indicated were reviewed retrospectively. In 44 patients with well-preserved hepatic reserve, the shunt was used as a long-term bridge to transplantation (shunt group 1). The remaining 27 patients with shunts were not transplant candidates mainly because of uncontrolled alcoholism or advanced age (shunt group 2). Survival of both shunt groups was compared to that of 180 adult patients with a history of variceal bleeding who underwent transplantation soon after referral., Results: Because of their more advanced liver disease, the liver transplant group had a higher operative mortality rate (19%) than did either of the shunt groups (5% and 7%, respectively) (p < 0.02). Kaplan-Meier survival analysis showed better survival in shunt group 1 (seven patients thus far transplanted) than in either the liver transplant group or shunt group 2 during the early years and superior survival of shunt group 1 and the liver transplant group as compared to shunt group 2 during the later years of the analysis. Only two patients from shunt group 1 have died of late postoperative hepatic failure without benefit of liver transplantation., Conclusions: A shunt may serve as an excellent long-term bridge to liver transplantation in patients with well-preserved hepatic reserve. Shunt surgery still plays an important role in treatment of selected patients with variceal bleeding who are not present or future transplant candidates.

It is not well understood whether posttransplant diabetes mellitus (PTDM) following orthotopic liver transplantation (OLTx) alters postoperative morbidity. This study was designed to evaluate this question. All adult patients who received an OLTx between July 1985 and March 1993 (n = 497) were evaluated by retrospective chart review for evidence of PTDM after OLTx. The patients identified with PTDM (n = 26) were case matched with nondiabetic OLTx recipients based on primary liver disease diagnosis, age, gender, date of first OLTx, and survival. Liver synthetic function, number and severity of rejection episodes, graft survival, total number of hospital days within the first year post-OLTx, renal function, and number and type of infection episodes were analyzed to assess differences in morbidity between the PTDM and control patients after OLTx. Of the 497 adult patients who underwent OLTx, 26 (5.2%) were identified as having PTDM within 1 month of discharge. Factors which identified individuals at higher risk for DM after OLTx included higher pre-OLTx fasting blood glucose (P = .04); lower body mass index after OLTx (P = .02); and cyclosporine rather than OKT3 induction (P = .009). Graft survival, synthetic function, and the total number of rejection episodes during the first year were not different between the two groups. The morbidity variables of total number of days in the hospital during the first 12 months, renal function, and type and number of infections were also similar between the two groups. In summary, 5.2% of adult patients developed DM within 1 month of OLTx. Pre-existing insulin resistance, postoperative stress, and immunosuppression medications all likely contribute to the development of overt hyperglycemia after OLTx. Although PTDM can be a consequence of OLTx, it does not have a significant impact on patient outcome in the first year after OLTx.

A successful liver/small intestinal transplantation with a blood group O donor to a blood type A recipient is described. Mild graft versus host disease developed, manifested by hemolysis, but did not result in graft loss or patient mortality. This suggests that minor ABO incompatibility may be tolerated with intestinal transplantation, despite the transplantation of large amounts of lymphoid tissue.

Background: The incidence of second malignancies is markedly increased following transplantation of solid organs. However, the development of Hodgkin's disease has been described relatively infrequently in this setting, and there is little clinical information on these patients and few details on management., Patients and Methods: We have reviewed the pathologic specimens and clinical history of four patients who developed Hodgkin's disease following transplantation of solid organs., Results: Hodgkin's disease appeared 26-68 months following transplantation of the kidney (2 cases), liver, and heart. Three cases demonstrated evidence of Epstein-Barr virus (EBV) in Reed-Sternberg cells. One case appears to have arisen after a previous EBV-driven polymorphous lymphoproliferation. Hodgkin's disease was localized in three cases and disseminated in one. All patients achieved remission with standard therapy and continue in remission between 9 and 61 months after therapy. Graft function was preserved in all patients., Conclusion: Hodgkin's disease occurring in the post-transplantation period should probably be treated like Hodgkin's disease in non-immunosuppressed patients. Prolonged disease-free survival is possible and function of the transplanted organ can be preserved.

Objective: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation., Methods: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations., Results: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had mild to moderate pulmonary dysfunction and one moderate to severe pulmonary dysfunction. All patients required pancreatic enzyme replacement, and four patients required insulin for diabetes mellitus. The 1-year survival rate was 75%, with no deaths related to septic events. Mean time of follow-up the six operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in those serially tested, showed that forced expiratory volume in 1 second was maintained or improved and that forced vital capacity improved after transplantation. Mutation analysis showed the following genotypes: four patients, delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta F508/unknown., Conclusions: Despite the high risk of transplantation, these encouraging results indicate that liver transplantation should be considered for patients with cystic fibrosis and complications of end-stage liver disease. We could not demonstrate an unusual pattern of CF gene mutations in these patients with severe liver disease. It appeared that immunosuppressive agents did not have a deleterious effect on pulmonary function.

Although the incidence of spousal transmission of hepatitis C virus (HCV) in chronic carriers is extremely low (1.4% to 8%), hepatitis C recurrence after liver transplantation is common with markedly increased serum HCV RNA levels. Thus, partners of these patients may be at higher risk of acquiring infection. This study evaluates the prevalence of spousal transmission of hepatitis C after liver transplantation. Twenty-two of 25 couples who were eligible agreed to the retrospective study. Twenty-two patients (17 males, 5 females) and spouses (5 males, 17 females) were studied with respective mean ages of 50.2 years (35 to 65 years) and 46.9 years (33 to 66 years). Liver enzymes, second-generation enzyme-linked immunosorbent assay (ELISA) for antibody to HCV (anti-HCV) and HCV RNA by polymerase chain reaction (PCR), and branched DNA assay were performed. HCV-associated antibodies were detected in 1 of 22 (5%) spouses and 21 of 22 (95%) patients (P < .0001). Nineteen of 22 (86%) patients tested positive by PCR with a mean value of 16,218,100 Eq/mL (464,700 to 51,980,000). All spouses including the only ELISA anti-HCV positive spouse tested negative by PCR (P < .0001). Eight of 21 spouses tested negative for anti-HCV pretransplantation, (13 of 21 pretransplantation were not tested). Estimated mean duration of hepatitis C infection in patients was 14 years (3 to 40 years). Mean patient follow-up posttransplantation was 654.5 days (141 to 1,959 days). Mean duration of marriage was 22.6 years (2.5 to 46 years). No risk factors other than exposure to index patients were observed in spouses. The incidence of spousal transmission of HCV in liver transplantation remains low (5%) and similar to chronic carriers of HCV.