Liver Transplantation In Cirrhotic Patients Research Articles

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients: Erratum.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients: Erratum.

Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt (PVR-TIPS) Facilitates Liver Transplantation in Cirrhotic Patients with Occlusive Portal Vein Thrombosis.

Portal vein thrombosis (PVT) is a heterogeneous condition with multiple possible etiologies and to varying degrees has historically limited candidacy for liver transplant (LT) in the cirrhotic patient population due to resultant difficulties in constructing a robust portal vein anastomosis. While intraoperative approaches to managing PVT are well-described, methods which approximate normal portal physiology are not always feasible depending on the extent of PVT, and other nonphysiologic techniques are linked with substantial morbidity and poor long-term outcomes. Portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) creation is an efficacious method of restoring physiologic portal flow in cirrhotic patients prior to LT allowing for end-to-end PV anastomosis, and is the product of decades-long institutional expertise in TIPS/LT and the support of a multidisciplinary liver tumor board. To follow is a review of the pertinent pathophysiology of PVT in cirrhosis, the rationale leading to the development and subsequent evolution of the PVR-TIPS procedure, technical lessons learned, and a summary of outcomes to date.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

Predicting the available space for liver transplantation in cirrhotic patients: a computed tomography-based volumetric study.

Anthropometric parameters (weight, height) are usually used for quick matching between two individuals (donor and recipient) in liver transplantation (LT). This study aimed to evaluate clinical factors influencing the overall available space for implanting a liver graft in cirrhotic patients. In a cohort of 275 cirrhotic patients undergoing LT, we calculated the liver volume (LV), cavity volume (CV), which is considered the additional space between the liver and the right hypocondrium, and the overall volume (OV = LV + CV) using a computed tomography (CT)-based volumetric system. We then chose the formula based on anthropometric parameters that showed the best predictive value for LV. This formula was used to predict the OV in the same population. Factors influencing OV variations were identified by multivariable logistic analysis. The Hashimoto formula (961.3 × BSA_D-404.8) yielded the lowest median absolute percentage error (21.7%) in predicting the LV. The median LV was 1531ml. One-hundred eighty-five patients (67.2%) had a median CV of 1156ml (range: 70-7006), and the median OV was 2240ml (range: 592-8537). Forty-nine patients (17%) had an OV lower than that predicted by the Hashimoto formula. Independent factors influencing the OV included the number of portosystemic shunts, right anteroposterior abdominal diameter, model for end-stage liver disease (MELD) score > 25, high albumin value, and BMI > 30. Additional anthropometric characteristics (right anteroposterior diameter, body mass index) clinical (number of portosystemic shunts), and biological (MELD, albumin) factors might influence the overall volume available for liver graft implantation. Knowledge of these factors might be helpful during the donor-recipient matching.

Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy.

ObjectiveThe role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE.Materials and MethodsA total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05).ResultsWe found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT.ConclusionThe renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Transcatheter aortic valve replacement (TAVR) as bridge therapy restoring eligibility for liver transplantation in cirrhotic patients.

Severe aortic stenosis is a widespread valve disease, constituting a contraindication to organ transplantation due to cardiovascular morbidity and projected mortality. Mortality after conventional surgical aortic valve replacement in cirrhotic patients depends upon the Child-Pugh class. In the past few years, transcatheter aortic valve replacement has progressively become the treatment of choice for high-risk patients with severe aortic stenosis. Here, we report the cases of 3 cirrhotic patients who became eligible for liver transplantation after successful transcatheter aortic valve replacement as bridge therapy.

Revisiting the indications for liver transplantation in cirrhotic patients considering the long-term outcomes of cirrhotic patients.

In this study, we investigated long-term survival of cirrhotic patients without hepatocellular carcinoma (HCC) and the proper timing of liver transplantation in the era with recent progress of management. We first classified 217 non-transplant cirrhotic patients without HCC according to the long-term survival based on Child-Turcotte-Pugh (CTP) scores and the MELD scores. We then compared them with the survival after liver transplantation in 114 patients with liver cirrhosis. We classified into four groups (class A as CTP score of 5,6, B as 7,8, C as 9-12, D as 13-15) according to the long-term survival of the patients, the survivals of patients with class C and D were significantly worse compared with transplant patients (P<0.001 in each group). And we also classified into four groups based on the MELD scores (class A as MELD score of -8, B as 9-12, C as 13-19, D as 19-), the survivals of patients with class C and D were significantly worse compared with those of transplant patients (P<0.001 in each group). Considering the long-term survival of patients with liver cirrhosis, CTP score of 9 and/or MELD score of 13 could be a proper timing for liver transplantation.

Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients

Diabetes occurring as a direct consequence of loss of liver function is usually characterized by non-diabetic fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels and should regress after orthotopic liver transplantation (OLT). This observational, longitudinal study investigated the relationship between the time-courses of changes in all 3 direct determinants of glucose regulation, i.e., β-cell function, insulin clearance and insulin sensitivity, and diabetes regression after OLT. Eighty cirrhotic patients with non-diabetic FPG and HbA1c levels underwent an extended oral glucose tolerance test (OGTT) before and 3, 6, 12 and 24 months after OLT. The OGTT data were analysed with a mathematical model to estimate derivative control (DC) and proportional control (PC) of β-cell function and insulin clearance (which determine insulin bioavailability), and with the Oral Glucose Insulin Sensitivity (OGIS)-2 h index to estimate insulin sensitivity. At baseline, 36 patients were diabetic (45%) and 44 were non-diabetic (55%). Over the 2-year follow-up, 23 diabetic patients (63.9%) regressed to non-diabetic glucose regulation, whereas 13 did not (36.1%); moreover, 4 non-diabetic individuals progressed to diabetes (9.1%), whereas 40 did not (90.9%). Both DC and PC increased in regressors (from month 3 and 24, respectively) and decreased in progressors, whereas they remained stable in non-regressors and only PC decreased in non-progressors. Insulin clearance increased in all groups, apart from progressors. Likewise, OGIS-2 h improved at month 3 in all groups, but thereafter it continued to improve only in regressors, whereas it returned to baseline values in the other groups. Increased insulin bioavailability driven by improved β-cell function plays a central role in favouring diabetes regression after OLT, in the presence of a sustained improvement of insulin sensitivity. Diabetes occurring in cirrhosis as a direct consequence of loss of liver function should regress after transplantation of a new functioning liver, though the pathophysiological mechanisms are unclear. This is the first study evaluating the contribution of all 3 direct determinants of insulin-dependent glucose regulation using a sophisticated mathematical model. Results show that β-cell function is the key process governing favourable or detrimental changes in glucose regulation in cirrhotic patients undergoing transplantation, pointing to the need to develop therapies to sustain β-cell function in these individuals. ClinicalTrials.gov, NCT02038517.

Utility of Liquid Biopsy (CTCs) after Liver Transplantation in Cirrhotic Patients with Hepatocarcinoma

Introduction New markers associated with angiogenesis and tumor metastasis, such as circulating tumor cells (CTCs), are opening up new avenues in cancer management from the laboratory. The Aim of this work is to determine the number of CTCs in patients included in waiting list for liver transplantation of hepatocellular carcinoma and to study its possible association with the alpha fetoprotein tumor marker (AFP) and with clinical variables such as number of tumors, presence of tumor vascular invasion, waiting list time, time from diagnosis and post-transplant tumor recurrence. In addition, we intend to compare the pre-transplant levels of CTCs with those obtained one month, six months, one year and two years after the transplant. Materials and Methods Peripheral blood of 36 patients suffering hepatocellular carcinoma once included in waiting list for liver transplant was obtained. 29 of them were transplanted, 27 of whom had blood extracted one month after the transplant, 19 of them after 6 months and one year after the transplant and 11 of them two years after the transplant. In order to study the correlation between the concentration of CTCs and the concentration of AFP, number of tumors, time on waiting list and from diagnosis in the patients, the Rho Spearman test was used. The study of the association of the CTCs levels with vascular invasion and presence of post-transplant recurrence was conducted with Mann-Whitney U test. For the variation in the levels of CTCs before and after the transplant, the Wilcoxon (SPSS 15.0) test was used. Results The average concentration of CTCs in the 36 patients before transplant was 11.50 CTCs/10mL (RI=2.25-42). A statistically significant positive correlation was found between the pre-transplant levels of CTCs and the days on waiting list (Rho= 0,376 p=0,024). The CTCs were not correlated in a significant way with the AFP concentration, number of tumors and time since diagnosis. (p>0,05). Out of the 29 transplanted patients, 2 showed vascular invasion in liver. Differences in the levels of CTCs were found between the patients with and without vascular invasion (U=0,00 p=0,020), these being significantly higher in the patients with vascular invasion. However, no significant differences were found in the levels of CTCs of the patients with recurrence after transplantation (4 patients) as opposed to those who didn’t (U=42 p=0.611). Conclusions Our conclusion is that the levels of tumor cells in peripheral blood could be an unfavourable prognostic factor associated to longer waiting times and to the presence of vascular invasion by tumor with an increased risk of relapse and post-transplant metastasis. In addition, we can see how their levels decrease significantly after transplantation. However, it would be necessary to increase the number of patients in the study, as well as the follow-up time, in order to achieve greater clinical evidence for its utility.

Liver Transplantation and Liver Resection for Cirrhotic Patients with Hepatocellular Carcinoma: Comparison of Long-Term Survivals

BackgroundBoth liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively. MethodsClinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods. ResultsIn total, 364 and 141 patients underwent LT and LR for HCC in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59 underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P < .0001), but not mortality (3 vs. 1%, P = .165), was higher after LR than after LT for HCC within MC. In the period 1989–2004, overall survival (OS) was significantly higher in patients who underwent LT compared to LR for HCC within MC (5-year OS: 77 vs. 36%, P < .0001). Interestingly, in the more recent period 2005–2011, OS was comparable between LT and LR for HCC within MC (5-year OS: 73 vs. 61%, P = .07). ConclusionWe have noted an improvement of outcomes among patients selected for partial hepatectomy in recent years that were comparable to stable results after LT in cirrhotic patients with HCC. Whether those improvements are due to advances in liver surgery, optimized perioperative managament for patients with liver cirrhosis, and the development of modern multimodal treatment strategies for the recurrent lesions appears plausible.

CIRCULATING MICRORNA-615-5P AS A DIAGNOSTIC MOLECULAR MARKER IN EGYPTIAN PATIENTS WITH LIVER CIRRHOSIS

Background: Liver cirrhosis has emerged as a major cause of global health burden. The vast majority (80-90%) of HCCs develop in a cirrhotic liver. Liver cirrhosis and HCC due to chronic hepatitis C are among the main indications for liver transplantation. The confront in the 21st century is to prevent the need for liver transplantation in cirrhotic patients as much as possible. Due to the unique situation of hepatitis C virus (HCV) in Egypt, being plagued with the highest HCV prevalence in the world, a considerable increase was observed in the proportion of chronic liver disease in Egyptian patients. Liver biopsy has traditionally been the “gold standard” test; it is an invasive procedure with rare but potentially life-threatening complications. These limitations rapidly reduced its use to the sake of developing non-invasive methods as indices and imaging. Alpha fetoprotein (AFP) is seen as the commonest and feasible marker for assessing liver cirrhosis; however, it is not completely reliable because of its low specificity and sensitivity. In early cirrhosis, however, conventional imaging can lead to false-negative diagnosis so other strategies are urgently needed. Currently, lack of robust biomarkers still limits evaluation of hepatic failure and progression in chronic diseases, especially in HCV infection. Aim: the main objective of the present study was to evaluate the significance of a new, non-invasive molecular marker, microRNA-615-5p (miR-615-5p) in circulating blood for diagnosing liver cirrhosis arising from HCV infection. Methods: A total of 50 blood samples were collected; 30 samples from hepatic cirrhotic patients, 10 samples from chronic HCV hepatitis patients and 10 control samples. The level of circulating miRNA-615-5p was detected by RT-qPCR in all samples. Besides, miR-615-5p levels in relation to clinical laboratory parameters were explored. Results: The expression of circulating miR-615-5p was distinctly increased in hepatic cirrhosis with HCV chronic patients compared with control group (mean ± SE: 5.44±0.02, P < 0.01 and 4.9±0.01, P < 0.01, respectively). Receiver Operator Characteristic (ROC) curve analysis revealed much higher specificity and sensitivity for the circulating miR-615-5p in comparison to the traditional AFP. Conclusions: The results showed that miR-615-5p might be a potential molecular biomarker for diagnosing liver cirrhosis, implying that it could be even used as a novel non-invasive molecular biomarker for predicting HCV-related liver cirrhosis.

COMPARATIVE STUDY ON LIVER TRANSPLANTATION WITH AND WITHOUT HEPATOCELLULAR CARCINOMA WITH CIRRHOSIS: ANALYSIS OF MELD, WAITING TIME AND SURVIVAL

Background : Liver transplantation is the usual treatment for hepatocellular carcinoma.Aim:To analyze the MELD score, waiting time and three month and one year survival for liver transplantation in cirrhotic patients affected by hepatocellular carcinoma or not. Methods : This was a retrospective, observational and analytical study of 93 patients submitted to liver transplantation. Results : There were 28 hepatocellular carcinoma and 65 non-hepatocellular carcinoma patients with no differences related to age and sex distribution. The main causes of cirrhosis on hepatocellular carcinoma were hepatitis C virus (57.1%) and hepatitis B virus (28.5%), more frequent than non-hepatocellular carcinoma patients, which presented 27.7% and 4.6% respectively. The physiological and exception MELD score on hepatocellular carcinoma were 11.9 and 22.3 points. On non-hepatocellular carcinoma, it was 19.4 points, higher than the physiological MELD and lower than the exception MELD on hepatocellular carcinoma. The waiting time for transplantation was 96.2 days for neoplasia, shorter than the waiting time for non-neoplasia patients, which was 165.6 days. Three month and one year survival were 85.7% and 78.6% for neoplasia patients, similar to non-neoplasia, which were 77% and 75.4%.Conclusion:Hepatocellular carcinoma patients presented lower physiological MELD score, higher exception MELD score and shorter waiting time for transplantation when compared to non-hepatocellular carcinoma patients. Three month and one year survival were the same between the groups.

Liver transplantation in cirrhotic patients with portal vein thrombosis: A single centre experience

Liver transplantation in cirrhotic patients with portal vein thrombosis: A single centre experience

Impact of recipient age and preoperative fasting blood glucose level as the risk factors of living donor liver transplantation in cirrhotic patients in the recent comprehensive era with knowledge of indications: Recent status in a Japanese single center

Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P < 0.05 was considered statistically significant. In multivariate analysis, recipient age (hazard ratio = 1.188, P = 0.011) and FBG (hazard ratio = 1.009, P = 0.016) showed as significant independent factors. Theoretical mortalities were 9.2%, 21.9% and 51.7% in patients with normal FBG at 55, 60 and 65 years old, respectively, and 34.3% and 53.6% in patients with FBG of 150 and 200 mg/dL, respectively, at 60 years old. Recipient age and FBG remain important risk factors for LDLT in cirrhotic patients even in the recent era. These factors should be considered for selecting liver transplant candidates in cirrhotic patients.

OC-18 Liver transplantation in cirrhotic patients with MELD score

OC-18 Liver transplantation in cirrhotic patients with MELD score <18: a new model to predict drop-out from the waiting list

Comparison of central and mixed venous saturation during liver transplantation in cirrhotic patients: a pilot study

Liver transplantation is associated with important haemodynamic variations requiring cardiac output and oximetric data monitoring. The mixed venous saturation (SvO2) integrates parameters combining information about oxygen consumption, cardiac output and haemoglobin concentration. Central venous saturation (ScvO2) can be directly measured from blood drawn in the superior venous system via a central venous catheter. ScvO2 has been proposed as an alternative to SvO2 for intraoperative haemodynamic monitoring. The aim of the present study was to examine the level of agreement between SvO2 and ScvO2 during the preanhepatic and the neohepatic stage of liver transplantation in cirrhotic patients. After agreement from the regulatory authorities for medical research and having obtained informed consent, 30 patients with cirrhosis undergoing liver transplantation were prospectively included. Blood gas samples were simultaneously drawn from the arterial line, the right atrium port and the pulmonary artery port of the catheter: during the preanhepatic stage (two times) and two times 30-40 min after graft revascularization. Arterial saturation (SaO2), haemoglobin concentration, cardiac index, SvO2, ScvO2 and oxygen consumption, delivery and extraction (VO2, DO2 and EO2, respectively) were measured. A Bland-Altman test was used to determine bias and limits of agreement between SvO2 and ScvO2. Both parameters were considered to be equivalent if limits of agreement were within +/-5%. Bland-Altman analysis revealed a bias (limit of agreement) of -1.2% (-9.1 to 6.6%), -0.3% (-4.8 to 4%) and -2.1% (-12 to 7.8%) for the overall measurements and preanhepatic and postgraft reperfusion measurements, respectively. SvO2 decreased significantly between hepatectomy and reperfusion, whereas cardiac index, VO2, DO2 and EO2 showed significantly higher values after reperfusion. ScvO2 and SaO2 levels did not display different values between the two periods. Measurements of SvO2 and ScvO2 showed a good level of agreement during the preanhepatic stage, whereas the level of agreement was low after liver graft reperfusion. The increase of VO2 associated with the decrease of SvO2 and the stability of ScvO2 between the two periods suggest an incomplete mixing of splanchnic venous blood into the right atrium. In addition, our samples were taken from the right atrium, which is not possible using a conventional central venous catheter, as the tip must lie in the superior vena cava and not in the right atrium. ScvO2 cannot be considered equivalent to SvO2 for the haemodynamic monitoring of patients with cirrhosis undergoing liver transplantation.

Liver Transplantation in Cirrhotic Patients With Hepatocellular Carcinoma and Concomitant HIV Infection: Two More Reasons to Accept or to Deny?

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with an incidence rate 2- to 3-fold higher in developing countries than in the industrialized world. Approximately 80% of all HCCs develop in cirrhotic livers with an annual incidence of 3% (1, 2). The most common underlying diseases are chronic viral hepatitis infection and chronic alcohol abuse. Curative treatment options are resection and liver transplantation (LT) (1, 2). LT is well established as a life-saving operation for patients with acute or chronic liver failure and is considered as the best treatment option for selected HCC patients even if extended criteria are applied (1). Imaging techniques such as computed tomography and magnetic resonance imaging have a cardinal role in the diagnosis of HCC, especially in the rare instances at which α-fetoprotein levels are negative and biopsy results are indeterminate. Despite improvements in imaging techniques, the diagnosis of small HCC (<2 or <1 cm) during the pretransplant evaluation remains difficult, resulting in a considerable rate of undetected HCC in liver explants (3). Unsuspected HCC found at the time of histologic examination of liver explants of patients transplanted for benign diseases is defined as “incidental HCC” (4). We report on an HIV-positive patient with end-stage liver disease (ESLD) who underwent LT at our Institution, with an incidental HCC found in his liver explant. The patient is a 61-year-old HIV-positive man with cirrhosis (Child-Turcotte-Pugh class-B) secondary to chronic hepatitis C viral (HCV) infection (genotype 1b). His highly active antiretroviral therapy (HAART) regimen included Lamivudin, Lopinavir, and Stavudin. Before LT, the CD4 T-cell count was 323 cells/μL and the HIV viral load less than 50 copies/mL. α-Fetoprotein levels were within the normal range. Preoperative staging was negative for tumor or metastases. The patient was listed for LT within Eurotransplant and after a waiting period of 466 days was transplanted with a deceased donor liver. The model for ESLD score at the time of LT was 13. The patient recovered uneventfully and was discharged on day 21. Immunosuppression after LT included tacrolimus and prednisone. The patient showed a stable CD4 T-cell count and undetectable HIV load under continuation of his pretransplant HAART. Histology showed two small (0.7 and 1.7 cm) moderately differentiated HCCs with no vascular invasion. Follow-up studies revealed no evidence of tumor recurrence. The patient remains in good general condition 15 months posttransplantation. More than 141 LT in HIV-positive patients, 25 cases of HIV-infected patients with concomitant viral hepatitis caused by HCV (n=19), hepatitis B viruses (HBV) (n=5) or both (n=1), and HCC are reported in the English literature (5). Morbidity resulting from chronic infection with HBV and HCV has become a leading cause of death in HIV-infected patients with synchronous chronic viral hepatitis. Since the introduction of HAART in 1996, the course of HIV-infection has changed dramatically. Therefore, HIV-positive patients are at greater risk of dying from complications of ESLD such as HCC, rather than HIV complications. Not only due to psychosocial reasons but also due to historically poorer outcomes before HAART, LT in the presence of HIV infection has been considered as contraindicated. Several series have demonstrated comparable graft and patient survival after LT between HIV-negative recipients and HIV patients with ESLD because of chronic viral hepatitis and have shown the effectiveness of LT as a therapeutic option in HIV patients affected by ESLD (6, 7). On the other hand, development of HCC especially in HBV- and HCV-related liver cirrhosis is another major indication for LT. The published results of LT in HIV-infected patients with HBV- and HCV-related HCCs using the Milan criteria are encouraging because recurrence was not observed (5, 7). LT in the HIV context requires a multidisciplinary approach and is complex and challenging. Because HAART has turned HIV infection into a chronic condition, transplant centers should accept to evaluate HIV-positive – HBV/HCV coinfected patients, for both medical and ethical reasons. The presence of HCC represents an additional reason to transplant these patients, given that tumor characteristics are within the accepted criteria. Spiridon Vernadakis1 Zoltan Mathe1 Gernot M. Kaiser1 Jürgen W. Treckmann1 Susanne Beckebaum1 Fuat H. Saner1 Andreas Paul1 Georgios C. Sotiropoulos1 1 Department of General, Visceral and Transplantation Surgery University Hospital Essen, Germany

Aggravation of Mitral Regurgitation by Calcium Administration in a Patient With Hypertrophic Cardiomyopathy During Liver Transplantation: A Case Report

Aggravation of mitral regurgitation (MR) due to left ventricular outflow tract obstruction (LVOTO) is likely to occur during liver transplantation in cirrhotic patients with hypertrophic cardiomyopathy (HCMP). Moreover, calcium administration following severe hypocalcemia due to inadequate citrate metabolism and massive transfusion may induce MR aggravation with LVOTO in such patients. Herein we have described a cirrhotic patient with HCMP in whom MR was aggravated due to LVOTO resulting from inadvertent rapid administration of calcium during liver transplantation.

The difficulty in timing for liver transplantation in cirrhotic patients coinfected with HIV: In search for a prognosis score

The difficulty in timing for liver transplantation in cirrhotic patients coinfected with HIV: In search for a prognosis score

MELD-XI: A rational approach to “sickest first” liver transplantation in cirrhotic patients requiring anticoagulant therapy

Priority for "sickest first" liver transplantation (LT) in the United States is determined by the model for end-stage liver disease (MELD). MELD is a good predictor of short-term mortality in cirrhosis, but it can overestimate risk when international normalized ratio (INR) is artificially elevated by anticoagulation. An alternate prognostic index omitting INR is needed in this situation. We retrospectively analyzed survival data for 554 cirrhotic veterans referred for consideration of LT prior to December 1, 2003 (training group). Using logistic regression we derived a predictive formula for 90-day pretransplant mortality incorporating bilirubin and creatinine but omitting INR. We normalized this formula to the same scale as MELD using linear regression. This yielded MELD-XI (for MELD excluding INR) = 5.11 Ln(bilirubin) + 11.76 Ln(creatinine) + 9.44. Accuracy of MELD-XI was validated in a holdout group of 278 cirrhotic veterans referred after December 1, 2003, and in an independent validation dataset of 7,203 cirrhotic adults listed for LT in the United States between May 1, 2001, and October 31, 2001. MELD-XI and MELD correlated well in training, holdout, and independent validation cohorts (r = 0.930, 0.954, and 0.902, respectively). In the holdout cohort, c-statistics of MELD vs. MELD-XI for mortality were, respectively, 0.939 vs. 0.906 at 30 days;0.860 vs. 0.841 at 60 days; 0.842 vs. 0.829 at 90 days; and 0.795 vs. 0.797 at 180 days. In the independent validation dataset, c-statistics for MELD vs. MELD-XI as predictors of 90-day survival were, respectively, 0.857 vs. 0.843 in noncholestatic liver diseases and 0.905 vs. 0.894 in cholestatic liver diseases. Comparable MELD and MELD-XI scores were associated with comparable prognosis. In conclusion, MELD-XI, despite omission of INR, is nearly as accurate as MELD in predicting short-term survival in cirrhosis. In patients treated with oral anticoagulants, substitution of MELD-XI for MELD may permit more accurate assessment of risk and more rational assignment of "sickest first" priority for LT.