Adult Orthotopic Liver Transplant Recipients Research Articles

Predictive Value of Fatty Liver Index for Long-Term Cardiovascular Events in Patients Receiving Liver Transplantation: The COLT Study.

Cardiovascular disease (CVD) is the leading cause of early mortality in orthotopic liver transplantation (OLT) patients. The fatty liver index (FLI) is strongly associated with carotid and coronary atherosclerosis, as well as cardiovascular mortality, surpassing traditional risk factors. Given the lack of data on FLI as a predictor of cardiovascular events in OLT recipients, we conducted a retrospective study to examine this topic. We performed a multicenter retrospective analysis of adult OLT recipients who had regular follow-up visits every three to six months (or more frequently if necessary) from January 1995 to December 2020. The minimum follow-up period was two years post-intervention. Anamnestic, clinical, anthropometric and laboratory data were collected, and FLI was calculated for all patients. gov registration ID NCT05895669. A total of 110 eligible patients (median age 57 years [IQR: 50-62], 72.7% male) were followed for a median duration of 92.3 months (IQR: 45.7-172.4) post-liver transplantation. During this period, 16 patients (14.5%) experienced at least one adverse cardiovascular event (including fatal and non-fatal myocardial infarction and stroke). Receiver Operating Characteristic (ROC) analysis identified a cut-off value of 66.0725 for predicting cardiovascular events after OLT, with 86.7% sensitivity and 63.7% specificity (68% vs. 31%; p = 0.001). Kaplan-Meier analysis showed that patients with FLI > 66 had significantly reduced cardiovascular event-free survival than those with FLI ≤ 66 (log-rank: 0.0008). Furthermore, multivariable Cox regression analysis demonstrated that FLI > 66 and pre-OLT smoking were independently associated with increased cardiovascular risk. Our findings suggest that FLI > 66 and pre-OLT smoking predict cardiovascular risk in adult OLT recipients.

Postoperative Trapped Lung After Orthotopic Liver Transplantation is a Predictor of Increased Mortality.

Pleural effusions are a common complication of orthotopic liver transplantation (OLT), and chronic post-OLT pleural effusions have been associated with worse outcomes. Furthermore, “trapped lung” (TL), defined as a restrictive fibrous visceral pleural peel preventing lung re-expansion, may have prognostic significance. We performed a retrospective analysis of adult OLT recipients over a 9-year period at UCLA Medical Center. Post-OLT patients with persistent pleural effusions, defined by the presence of pleural fluid requiring drainage one to 12 months after OLT, were included for analysis. Outcomes for patients with and without TL were compared using univariate and multivariate analysis. Of the 1722 patients who underwent OLT, 117 (7%) patients met our criteria for persistent postoperative pleural effusion, and the incidence of TL was 21.4% (25/117). Compared to patients without TL, those with TL required more surgical pleural procedures (OR 59.8, 95%CI 19.7–181.4, p < 0.001), spent more days in the hospital (IRR 1.56, 95%CI 1.09–2.23, p = 0.015), and had a higher risk of mortality (HR 2.47, 95%CI 1.59–3.82, p < 0.001) following transplant. In sum, we found that post-OLT TL was associated with higher morbidity, mortality, and healthcare utilization. Future prospective investigation is warranted to further clarify the risk factors for developing postoperative pleural effusions and TL.

Post-Reperfusion Syndrome in Liver Transplantation: Does a Caval Blood Flush Vent Help?

BackgroundPost-reperfusion syndrome (PRS) during liver transplantation can range from a benign event to a profound hemodynamic excursion from baseline with significant morbidity. Multiple variables can be responsible for the diverse presentations. Over time, our group noticed that a blood flush of the liver graft via a caval vent (in addition to a standard chilled flush via the portal vein) appeared to result in a milder reperfusion effect. Attenuation of PRS via caval vent seemed to minimize hemodynamic instability and reduce metabolic derangements associated with reperfusion.Material/MethodsThis was a prospective observational pilot study of standard practice with the addition of lab values and hemodynamic evaluations. We methodically observed normal clinical flow in 20 adult orthotopic liver transplant recipients. We analyzed blood and fluid samples at set time intervals during the peri-reperfusion phase.ResultsSixteen out of 20 patients received a blood flush via caval venting. Mean arterial pressure (MAP) and heart rate were better preserved in the patient population that received a caval blood flush vent. Elevations in central venous pressure (CVP) were similar between the 2 groups. Lab values (blood gas, electrolyte, and hemoglobin) of the patients’ blood were similar, with no notable differences. Analysis of the initial blood flushed through the liver graft proved to be hypothermic, acidotic, and hyperkalemic.ConclusionsPre-reperfusion caval venting in liver transplantation (in addition to a portal vent and a chilled LR/albumin portal flush solution) appears to have favorable hemodynamic effects. The literature on this technique is sparse and larger studies are needed.

Low Postoperative Platelet Counts Are Associated with Major Morbidity and Inferior Survival in Adult Recipients of Orthotopic Liver Transplantation

BackgroundPlatelets (PLT) play an essential functional role in cellular injury and liver regeneration following partial hepatectomy and orthotopic liver transplantation (OLT). Here, we investigated the association of postoperative PLT counts with short- and long-term outcomes in adult OLT recipients. MethodsThree hundred consecutive patients from our prospective OLT database were analyzed retrospectively (May 2010–November 2017). Ninety-day post-OLT complications were graded using the Clavien-Dindo (CD) classification and quantified by the comprehensive complication index (CCI). To determine the prognostic accuracy of PLT counts, the area under the receiver operating characteristic curve (AUROC) was calculated for major complications (CD ≥ 3b). Parametric and non-parametric tests were applied for subgroup analyses. Uni- and multivariable logistic regression analyses were performed to identify risk factors for major complications. Graft and patient survival were analyzed using the Kaplan-Meier method as well as uni- and multivariable Cox regression analyses. ResultsPostoperative day 6 PLT counts < 70 × 109/L (POD6-70) were identified as the best cutoff for predicting major complications (AUROC = 0.7; p < 0.001; Youden index 0.317). The stratification of patients into low- (n = 113) and high-PLT (n = 187) groups highlighted significant differences in major complications (CCI 68 ± 29 vs. 43 ± 28, p < 0.001); length of hospital and intensive care unit (ICU) stay (53 ± 43 vs. 31 ± 25, p < 0.001; 21 ± 29 vs. 7 ± 11, p < 0.001, respectively) and estimated procedural costs. POD6-70 was associated with inferior 5-year graft survival. Multivariable logistic regression analysis identified POD6-70 as an independent predictor of major complications (odds ratio 2.298, confidence intervals 1.179–4.478, p = 0.015). ConclusionIn OLT patients, a PLT count on POD6 of less than 70 × 109/L bears a prognostic significance warranting further investigations.

The Utility of ECMO After Liver Transplantation: Experience at a High-volume Transplant Center and Review of the Literature.

Extracorporeal membrane oxygenation (ECMO) artificially supports respiratory and cardiac function when conventional techniques fail. ECMO has been described as a treatment modality for acute pulmonary and cardiac failure following orthotopic liver transplantation (OLT). Here, we present a series of adult OLT recipients placed on ECMO after transplantation for both respiratory and cardiac indications and review the literature on the role of ECMO in the setting of OLT. For the patient series, we cross-referenced all patients who underwent OLT at our institution between 2007 and 2018 with the ECMO database of our institution and described these cases. For the literature review, we identified cases and series that described the use of ECMO after liver transplantation in adult recipients. A total of 1792 patients underwent OLT. Eight patients were placed on ECMO (0.4%), 5 men and 3 women aged 28 to 68 years (4 venovenous and 4 venoarterial). Three of (38%) 8 patients survived to discharge and are alive today. In the literature, we identified 3 series and 12 case reports of ECMO following OLT, with the majority of the literature derived from the Asian OLT experience. ECMO following liver transplantation should be considered as a viable rescue strategy in patients with severe cardiopulmonary failure. ECMO is particularly effective if the cause of cardiopulmonary failure is recognized promptly and is thought to be transient. This is the largest series in the United States and demonstrates a 38% survival rate, which is comparable to other reports in the literature from Asia.

Early cytokine signatures of ischemia/reperfusion injury in human orthotopic liver transplantation.

BACKGROUND. Orthotopic liver transplant (OLT) is the primary therapy for end-stage liver disease and acute liver failure. However, ischemia/reperfusion injury (IRI) can severely compromise allograft survival. To understand the evolution of immune responses underlying OLT-IRI, we evaluated longitudinal cytokine expression profiles from adult OLT recipients before transplant through 1 month after transplant. METHODS. We measured the expression of 38 cytokines, chemokines, and growth factors in preoperative and postoperative recipient circulating systemic blood (before transplant and 1 day, 1 week, and 1 month after transplant) and intraoperative portal blood (before and after reperfusion) of 53 OLT patients and analyzed this expression in relation to biopsy-proven IRI (n = 26 IRI+; 27 IRI-), clinical liver function tests early (days 1-7) after transplant, and expression of genes encoding cytokine receptors in biopsies of donor allograft taken before and after reperfusion. RESULTS. Bilirubin and arginine transaminase levels early after transplant correlated with IRI. Fourteen cytokines were significantly increased in the systemic and/or portal blood of IRI+ recipients that shifted from innate to adaptive-immune responses over time. Additionally, expression of cognate receptors for 10 of these cytokines was detected in donor organ biopsies by RNAseq. CONCLUSION. These results provide a mechanistic roadmap of the early immunological events both before and after IRI and suggest several candidates for patient stratification, monitoring, and treatment. FUNDING. Ruth L. Kirschstein National Research Service Award T32CA009120, Keck Foundation award 986722, and a Quantitative & Computational Biosciences Collaboratory Postdoctoral Fellowship.

Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case of chronic hepatitis E was observed in patients with normal liver enzymes, indicating that general screening of all OLT recipients is not necessary. However, if chronic hepatitis E develops, it can be treated efficiently with ribavirin.

Acyclovir versus valganciclovir for preventing cytomegalovirus infection in intermediate-risk liver transplant recipients.

Cytomegalovirus (CMV) is an opportunistic infection that causes profound morbidity and mortality after orthotopic liver transplant (OLT). The CMV immunoglobulin G serostatuses of donors and recipients are the main factors influencing risk for development of CMV infection after transplant. To compare acyclovir and valganciclovir for preventing CMV infection after OLT. Retrospective assessment of adult OLT recipients at intermediate risk for CMV infection at New York Presbyterian Hospital. All patients received ganciclovir 5 mg/kg intravenously every 12 hours or valganciclovir 900 mg orally every 12 hours for 7 days after transplant. On postoperative day 8, patients received antiviral prophylaxis according to risk stratification: acyclovir 800 mg orally 3 times daily in donor seronegative/recipient seropositive (D-/R+) patients or valganciclovir 900 mg orally once daily in donor seropositive/recipient seropositive (D+/R+) patients. Composite incidence of CMV infection, syndrome, or tissue-invasive disease. Of 275 OLT recipients, 89 were at intermediate risk for CMV infection (29 D-/R+, 60 D+/R+). CMV infection, syndrome, or tissue-invasive disease occurred in 1 patient (3%) in the D-/R+ group and 5 patients (8%) in the D+/R+ group (P=.66). One patient (3%) in the D-/R+ group had a CMV infection develop. Five D+/R+ recipients (8%) had CMV infection; 3 of them had CMV syndrome (5%), 1 had CMV hepatitis (1.6%), and the other had CMV esophagitis (1.6%); all events occurred after prophylaxis was discontinued. The rates of CMV infection were similar in D-/R+ patients treated with acyclovir and D+/R+ patients receiving valganciclovir. This risk-stratified approach to viral prophylaxis after OLT resulted in an acceptable rate of CMV infection in D-/R+ recipients and may avoid the costs and adverse effects associated with valganciclovir therapy.

Liver Transplantation for Unresectable Hepatocellular Carcinoma in Elderly Patients: What to Expect

IntroductionElderly patients have orthotopic liver transplantation (OLT) outcomes comparable to younger individuals. However, it is undefined whether such results are also seen in those with unresectable hepatocellular carcinoma (HCC). The primary endpoints of this study were overall survival (OS), retransplantation rate, and disease-free survival (DFS) in OLT recipients with HCC and aged ≥65 years compared with those aged <65 years. Patients and MethodsThis was a single-center retrospective review of a cohort of adult deceased-donor OLT recipients due to unresectable HCC within the Milan criteria from May 2006 through March 2013. Demographic and clinical variables and outcomes of patients aged ≥65 years were compared with those aged <65 years. ResultsThirty-seven individuals ≥65 years of age (group 1) and 141 individuals <65 years of age (group 2) were analyzed. OS (group 1 vs group 2) at 1 year (78% vs 81%), 3 years (64% vs 70%), and 5 years (64% vs 66%) (P = .49) was comparable. Retransplantation rates were also similar (group 1: 13.5%; group 2, 10.6% [P = .61]). DFS (group 1 vs group 2) at 1 year (100% vs 95%), 3 years (91% vs 92%), and 5 years (91% vs 92%) (P = .56) was also not significantly different between groups. On multivariate analysis, age >65 years was not an independent predictor of OS or DFS. ConclusionsPatients aged ≥65 years with HCC presented with outcomes similar to their younger counterparts. Chronologic age is not a good predictor of outcome, and transplantation is feasible if overall clinical conditions and comorbidities allow.

Pharmacist-Driven CNI-Minimization Protocol to Preserve Renal Function Post-Liver Transplantation.

Purpose: Preservation of renal function following orthotopic liver transplantation (OLT) through calcineurin inhibitor (CNI)-minimization is an established clinical objective. The use of everolimus (EVR) to reduce tacrolimus (TAC) exposure was recently shown to provide superior renal function 24 months post-OLT compared with patients on standard TAC therapy. Methods: We performed a retrospective cohort study of adult OLT recipients transplanted in 2013 who were placed on a CNI-minimization regimen (TAC trough goal 3-5 ng/mL) with EVR (goal trough 3-8 ng/mL). Clinical pharmacists prospectively identified patients based on eGFR (30-70 mL/min), absence of proteinuria (urine protein <500mg/day), total cholesterol <350 mg/dL, and fasting triglycerides <500 ng/dL. The primary endpoint was the change in renal function from CNI-minimization, as assessed by eGFR at 4 and 12 weeks post-conversion. Renal function was compared with a cohort of patients meeting the same criteria, who remained on standard TAC therapy (goal trough 6-10 mg/mL). Results: In total, 21 patients met criteria and 14 were converted to EVR. There were no differences in race, sex, CMV risk, hepatocellular carcinoma or primary diagnoses between groups, and there were no acute rejections in either arm. MELD, cold ischemic time, and creatinine at transplant were well matched. Median time to conversion was 113 days, and this was used as reference time in the control arm. Baseline eGFR was lower in the EVR arm (55.4 vs. 46.8 mL/min, p = 0.025) but was not significantly different following conversion.Figure: No Caption available.There was a significantly higher change in eGFR in week 4 and week 12 in the EVR conversion arm (-6.4 mL/min in the control arm vs +6.2 mL/min in the EVR arm, p = 0.021). No treatment-limiting adverse events occurred in either group through 12 weeks of follow-up. Conclusion: We note a significant improvement in renal function for patients on EVR compared to those on standard TAC, demonstrating successful implementation of pharmacist-driven CNI-minimization strategy following OLT. DISCLOSURES:Horwedel, T.: Speaker's Bureau, Novartis. Chapman, W.: Speaker's Bureau, Novartis.

Coronary artery disease and its risk factors in patients presenting for liver transplantation

Study ObjectiveTo determine the distribution of coronary artery disease (CAD) and its risk factors across the various etiologies of end-stage liver disease, and to elucidate the relationship between severe alcohol consumption and CAD. DesignRetrospective multicenter study analysis. SettingNational Standard Transplant Analysis and Research file data. MeasurementsData from all primary adult orthotopic liver transplant recipients during the period from 2004 through 2006 were studied. Data were divided into 5 groups according to each patient’s etiology of end-stage liver disease. The prevalence of CAD and the distribution of its risk factors were compared among groups. Main results17,482 cases were studied. The incidence of CAD was highest in nonalcoholic hepatic steatosis (7.4%) and lowest in biliary cirrhosis (1.7%). No difference in prevalence of CAD and its risk factors was noted between the viral and alcoholic etiologies (Hepatitis C 2.7%, Hepatitis B 2.3%, and alcoholic cirrhosis 2.9%). ConclusionsPrevalence of CAD and the distribution of CAD risk factors in patients with severe alcohol consumption were similar to patients with viral hepatitis. CAD was most prevalent in patients with hepatic steatosis. This study argues against the notion of decreased expression and progression of CAD in patients with alcoholic cirrhosis presenting for liver transplantation.

Effect of Tacrolimus on Survival in Hepatitis C–Infected Patients After Liver Transplantation

The observation that cyclosporine inhibits HCV replication in vitro has led some programs to use cyclosporine as the calcineurin inhibitor (CNI) of choice after orthotopic liver transplantation (OLT). Previous studies comparing outcomes with different CNIs used small HCV cohorts or had short-term follow-up. We examined patient survival and fibrosis progression in all HCV-infected adult primary OLT recipients from 1995 to 2004 at the Annette C. and Harold C. Simmons Transplant Institute (n = 516). Patients were categorized by their CNI on day 7 post-OLT, and they were excluded if they died before day 14. Patient and donor age, sex, race, and prevalence of cytomegalovirus infection post-OLT were similar in the tacrolimus and cyclosporine patients. As expected, acute cellular rejection and steroid-resistant rejection were less common in tacrolimus-treated patients. Although no difference in 1-year survival was seen, tacrolimus patients (n = 268) had superior 5-year survival compared to cyclosporine patients (n = 248) (75% vs. 67%; P = 0.02). Fibrosis progression was no different between the groups. In our retrospective analysis of 516 post-OLT patients, tacrolimus improved long-term survival compared to cyclosporine in HCV-infected patients, although it did not impact HCV fibrosis progression.

Differences in health-related quality of life scores after orthotopic liver transplantation with respect to selected socioeconomic factors

One of the current ultimate goals of orthotopic liver transplantation (OLT) is the improvement of patients' health-related quality of life (HRQOL). The purpose of this study was to look at the effects of socioeconomic and demographic differences on the short-term and long-term HRQOL outcomes of OLT recipients. Three hundred three adult OLT recipients who were seen at the University of California Los Angeles were administered the Medical Outcomes Study Short Form 36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ), and a demographic survey. A parsimonious model of 12 socioeconomic and demographic predictors was identified. Their simultaneous influence on each SF-36 and CLDQ HRQOL domain score was evaluated with multivariate linear regression and backward selection. Hepatitis C virus impaired HRQOL; this was shown in the SF-36 Vitality and Bodily Pain domains and in most CLDQ domains. Females experienced more HRQOL impairment only within the CLDQ Abdominal Symptoms domain. OLT recipients who were married had better SF-36 Role-Emotion domain scores. OLT recipients with more than 12 years of education had better SF-36 Physical Functioning scores. Employed OLT recipients had less HRQOL impairment; this was evidenced by better scores in multiple domains of the SF-36 and the CLDQ. OLT patients with health maintenance organization or preferred provider organization insurance had higher HRQOL scores within almost all SF-36 and CLDQ domains. Patients with a mix of public and private insurance had significantly higher HRQOL scores in comparison with those with only public insurance. Identifying patients at higher risk for worse HRQOL scores, less satisfaction with OLT results, and greater problems with fatigue or mental health stressors will assist transplant centers in using their medical teams to develop early interventions and multidisciplinary approaches to improve HRQOL outcomes after OLT.

Risk factors and incidence of de novo malignancy in liver transplant recipients: a systematic review

Orthotopic liver transplant (OLT) is an established life saving procedure for both acute and chronic liver failure, but incidences and risk factors for development of these malignancies are yet to be established. To determine the incidences and risk factors associated with de novo malignancy after OLT. We performed a systematic review of relevant epidemiological studies available on MEDLINE, which provided information on the incidences and risk factors for the development malignancies in adult OLT recipients published from 1983 to 2009. All data was compiled from retrospective studies. Independent risk factors for the development of de novo malignancy in adult OLT recipients were identified to be statistically significant including immunosuppression, hepatitis C virus infection, smoking, alcoholic cirrhosis and sun exposure. OLT recipients with smoking and alcohol history are of particular risk for head and neck and lung cancers. Primary sclerosing cholangitis and inflammatory bowel disease were found to be independent risk factors for colon cancer. Adult OLT recipients are at increased risk for the development of post-transplant malignancies and obviates the need for surveillance protocols that are safe and cost-effective. OLT recipients should be advised on taking proper precautions in the sun, smoking cessation, and eliminating alcohol consumption. Given the emergence of alcoholic cirrhosis as a leading indication for liver transplantation, the early detection of lung and head and neck cancers is of particular importance.

Optimizing use of basiliximab in liver transplantation

Optimizing use of basiliximab in liver transplantation Carlo B Ramirez, Adam Bozdin, Adam Frank, Warren Maley, Cataldo DoriaDepartment of Surgery, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Antibody induction therapy has not been part of standard immunosuppressive regimens in liver transplantation. However, in recent years there has been an upward trend in the use of antibody induction therapy in orthotopic liver transplantation (OLT), attributed mainly to the growing number of OLT recipients with renal dysfunction after the Model for End Stage Liver Disease (MELD) scoring system was adopted in 2002. Basiliximab, a chimeric monoclonal antibody, is the most frequently used induction antibody in OLT. Basiliximab targets the alpha chain of interleukin-2 receptors in activated T-lymphocytes, inhibiting T-lymphocyte proliferation responsible for acute cellular rejection. Basiliximab (given in two 20 mg doses intravenously on post OLT day 0 and 4) has an excellent efficacy and safety profile. Basiliximab induction also allows early steroid withdrawal or avoidance, as well as delayed introduction and minimization of calcineurin inhibitors (CNI) in the setting of renal insufficiency. Although its long-term effect on hepatitis C virus (HCV) recurrence post OLT is currently unknown, studies using basiliximab induction in steroid-free protocols suggest no harmful effect on histologic HCV recurrence and survival rates. Basiliximab is a well tolerated, effective and safe anti-rejection drug in pediatric and adult OLT recipients when given in conjunction with a CNI-based immunotherapy.Keywords: liver transplantation, basiliximab, acute cellular rejection, immunosuppression, steroids

Low recurrence of preexisting extrahepatic malignancies after liver transplantation

The incidence of de novo malignancies is increased in organ transplant recipients, and patients with hepatic carcinomas are at high risk for tumor recurrence after liver transplantation. Data about recurrent cancer after orthotopic liver transplantation (OLT) in patients with a history of nonhepatic malignancy are very limited. We retrospectively analyzed data from 606 adult OLT recipients and identified 37 patients (6.1%) with a preexisting extrahepatic malignancy. In the same group, 43 patients (7.0%) developed de novo cancer. Preexisting malignancies included 26 solid tumors and 11 hematological malignancies, including 7 patients with Budd-Chiari syndrome due to myeloproliferative disorders (MPDs). Patients had been selected for OLT because of the expected good prognosis of their preexisting malignancy. Except for 3 patients, recipients were tumor-free at OLT. The median interval from tumor diagnosis to OLT was 44 months (range, <1-321). After a median follow-up of 66 months post transplantation (range, 4-131), all but 1 recipient with incidental colon carcinoma were free of recurrence. No patient with MPD showed leukemic transformation, whereas a patient with neurofibromatosis experienced growth of skin fibromas. Our data and an included review of published OLT recipients with preexisting malignancies have enabled us to show that recurrence rates are comparable for nontransplanted patients and renal-transplant recipients. In conclusion, cancer recurrence is low if OLT recipients are carefully selected. Therefore, previous extrahepatic malignancy should not be considered a contraindication for OLT per se, but the oncologic/hematologic prognosis should be considered, particularly with respect to the current 5-year survival rate of OLT.

The use of coronary stent in hepatic artery stenosis after orthotopic liver transplantation

Purpose This retrospective study was undertaken to evaluate the effectiveness of coronary stent placement in hepatic artery stenosis after orthotopic liver transplantation (OLT). Materials and methods Of 430 consecutive adult orthotopic liver transplant recipients between November 2003 and September 2005, 17 had hepatic artery stenosis (HAS). Fourteen of them underwent coronary stent placement in the HAS. The technical results, complications, hepatic artery patency and clinical outcome were reviewed. Results Technical and immediate success was 100%. After a mean follow-up of 159.4 days (range, 9–375 days), all patients obtained patent hepatic arteries except 2 patients occurred hepatic artery restenoses at 26 and 45 days after stent placement, respectively. Kaplan–Meier curve of patency showed cumulated stent patency at 3, 6, and 12 months of 78%, 58% and 45%, respectively. During the follow-up, 8 patients survived, 5 died of septic multiple-organ failure, 1 received retransplantation because of refractory biliary infection. Hepatic artery dissection induced by a guiding catheter occurred in one patient and was successfully treated with a coronary stent. Conclusion Hepatic artery stenosis after OLT can be successfully treated with coronary stent placement with low complication rate and an acceptable 1-year hepatic artery patency rate.

Tolerance: Is It Worth the Risk?

The success of orthotopic liver transplantation (OLT) has been limited by the adverse effects of immunosuppression. The purpose of this study was to determine the safety and feasibility of withdrawing immunosuppression in OLT recipients to achieve tolerance. Eighteen adult OLT recipients in our steroid-free protocol without rejection were selected for this protocol. All patients chosen for this trial were on tacrolimus monotherapy with normal liver function tests (LFTs). Tacrolimus was weaned as long as LFTs remained stable. Weaning was halted for elevations of liver enzymes and tacrolimus was increased to the last dosage at which the patients had normal LFTs. Rejection was treated by increasing tacrolimus to levels of 10-15 ng/ml. Mycophenolate mofetil (MMF) or sirolimus was added if there was severe rejection by biopsy. Steroids were used if there was no improvement. One patient has been weaned off immunosuppression. Three additional patients were weaned completely off but had tacrolimus resumed because of mild elevations in LFTs. Eleven of 18 (61%) patients had rejection. Two patients required steroid therapy and one required rabbit antithymocyte globulin in addition to MMF and steroids. One of the patients with rejection developed diabetes and one patient had renal failure, which subsequently resolved. One patient died following a stroke. Clinical tolerance can be achieved in a minority of patients, even when being maintained on minimum immunosuppression. The potential benefit of achieving tolerance must be weighed against the risks of rejection therapy in patients doing well on low-dose immunosuppression.

Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy.

Background In 2001, we published early results of a prospective randomized trial of 71 patients who received either steroids or rabbit antithymocyte globulin (RATG) for orthotopic liver transplantation (OLT). We now report follow-up on these patients and additional patients undergoing steroid-free OLT. Methods A total of 119 adult OLT recipients were prospectively randomized to receive either methylprednisolone 1,000 mg followed by a 3-month steroid taper or a steroid-free regimen of RATG 1.5 mg/kg during the anhepatic phase followed by a 1.5 mg/kg dose on posttransplant day 1. Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil in both groups. Mycophenolate mofetil was weaned over 3 months in the first 71 patients and over 2 weeks in the last 48 patients, achieving tacrolimus monotherapy by 2 weeks posttransplant. Subsequently, a group of 24 sequential OLT recipients received the steroid-free (RATG) protocol. Endpoints of the study were survival, rejection, infectious complications, posttransplant diabetes, and recurrent hepatitis C virus. Results One-year patient survival was 85% in each group of the prospective randomized trial with a mean follow-up of 18.5 months. One-year graft survival was 82% in the RATG group and 80% in the steroid group (P = not significant). Patient and graft survival of the 24 nonrandomized RATG patients was 96% with a mean follow-up of 3 months. The incidence of rejection was not significantly different; however, 50% of the patients in the steroid group required pulse steroids to reverse the rejection compared with only one patient (1.6%) in the RATG group (P= 03). The incidence of cytomegalovirus infection (P < .05) and posttransplant diabetes was higher in the steroid group (P = .03). There was a trend toward decreased severity of hepatitis C virus in the RATG group. Conclusions Steroid-free liver transplantation using RATG and early tacrolimus monotherapy effectively reduces immunosuppression-related complications with excellent survival.

Hepatic artery thrombosis and intraoperative hepatic artery flow rates in adult orthotopic liver transplantation.

Thrombosis of the hepatic artery following orthotopic liver transplantation (OLT) can be a devastating com-plication impacting on recipient outcome. The utility of routine intraoperative flow measurements of the hepatic artery in predicting subsequent hepatic artery thrombosis (HAT) is presented in this study. Data on all adult OLT recipients between July 1995 and May 2000 were analysed. This included the routine intra-operative flow measurements of both the hepatic artery and portal vein using a Doppler flow meter. Thirteen out of 198 (6.6%) instances of OLT were complicated by HAT. The mean and median flow rates of the hepatic artery in the OLT with HAT were 262 mL/min and 220 mL/min, respectively. These were significantly lower than the respective values of 436 mL/min and 400 mL/min in the OLT without HAT (P = 0.0036). This was independent of recipient age, sex, weight and intraoperative portal flow rates. However there was extensive overlap for the intraoperative hepatic artery flow rates obtained between the HAT and non-HAT groups. The risk of HAT was increased by a factor of 6 if the intraoperative hepatic artery flow rate was less than 200 mL/min. The average allograft survival was significantly lower in the HAT group at 373 days vs the non-HAT group at 763 days (P = 0.026). The routine use of intraoperative flow measurements of the hepatic artery may be a useful adjunct in identifying the hepatic artery reconstruction, which is at risk of subsequent HAT.