Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of OLT

  • patient undergoing olt
  • successful olt
  • undergoing olt

  • Terms modified by OLT

  • olt patient
  • olt recipient

  • Selected Abstracts

    EFNS guidelines on management of neurological problems in liver transplantation

    M. Guarino
    Neurological impairment after orthotopic liver transplantation (OLT) is common and represents a major source of morbidity and mortality. The diagnosis and management of neurological problems occurring after OLT are difficult and evidence-based guidelines for this task are currently lacking. A Task Force was set up under the auspices of the European Federation of Neurological Societies to devise guidelines to prevent and manage neurological problems in OLT. We selected six major neurological problems and approached them combining an evidence-based scientific literature analysis with a search of consensus by means of a Delphi process. Search results were translated into a series of recommendations constituting a basis for better care of patients with neurological complications after OLT. [source]

    Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: An intention-to-treat analysis,,

    HEPATOLOGY, Issue 3 2008
    Francis Y. Yao
    We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2,5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceeding T2 criteria who were enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein >1,000 ng/mL. Conclusion: Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome. (HEPATOLOGY 2008.) [source]

    Fractures and avascular necrosis before and after orthotopic liver transplantation: Long-term follow-up and predictive factors,

    HEPATOLOGY, Issue 4 2007
    Maureen M. J. Guichelaar
    With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. Conclusion: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients. (HEPATOLOGY 2007.) [source]

    Biliverdin therapy protects rat livers from ischemia and reperfusion injury

    HEPATOLOGY, Issue 6 2004
    Constantino Fondevila
    Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of ex vivo perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P-selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1,, tumor necrosis factor ,, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO-1 expression, consistent with BV being an important mediator through which HO-1 prevents cell death. In conclusion, this study documents and dissects potent cytoprotective effects of BV in well-established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs. (HEPATOLOGY 2004;40:1333,1341.) [source]

    Review article: the current management of acute liver failure

    D. G. N. CRAIG
    Aliment Pharmacol Ther,31, 345,358 Summary Background, Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. Aim, To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Methods, Literature review using Ovid, PubMed and recent conference abstracts. Results, Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and ,buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Conclusion, Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT. [source]

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

    Eric Chak
    Abstract 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. [source]

    Gender-incompatible liver transplantation is not a risk factor for patient survival

    Frank Lehner
    Abstract Background/Aims: Clinical data may be suggestive for differences in patient survival in gender-incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively linked to circulating hormones. We therefore investigated patient survival as well as metabolism of steroids to identify possible causes of improved graft survival in gender-mismatched OLT. Methods: We examined our single-centre database of 1355 recipients of first liver transplants for overall patient survival by non-parametric and parametric analysis of multivariance taking the age of recipient and donor, ischaemia time, underlying liver disease and the time period of transplantation into account. Furthermore, the metabolism of androgens in gender-incompatible OLT was studied in cultures of primary human hepatocytes obtained from male and female patients. Results: Unlike previous studies we were unable to determine overall significant differences in patient survival in gender-incompatible OLT, even though a statistically significant improved patient survival was observed when male donor livers were transplanted into female recipients in univariant analysis (P=0.047). However, when the overall patient management was taken into account no difference in survival was determined in multivariant analysis. Importantly, the metabolism of testosterone did not differ between male and female hepatocyte cultures, except for the production of 6-,-hydroxy-testosterone (P<0.001). Conclusions: Taken collectively, clinical observations may tend to suggest a slightly improved patient survival in gender-incompatible OLT but this cannot be explained on the bases of androgen metabolism. Overall, we view gender-incompatible liver transplantation not to be a confounder in patient survival after OLT. [source]

    A comparison of liver transplantation outcomes in the pre- vs.

    post-MELD eras
    Summary Background:, The model for end stage liver disease (MELD)-based organ allocation system is designed to prioritize orthotopic liver transplantation (OLT) for patients with the most severe liver disease. However, there are no published data to confirm whether this goal has been achieved or whether the policy has affected long-term post-OLT survival. Aim:, To compare pre-OLT liver disease severity and long-term (1 year) post-OLT survival between the pre- and post-MELD eras. Methods:, Using the United Network of Organ Sharing database, we compared two cohorts of adult patients undergoing cadaveric liver transplant in the pre-MELD (n = 3857) and post-MELD (n = 4245) eras. We created multivariable models to determine differences in: (i) pre-OLT liver disease severity as measured by MELD; and (ii) 1-year post-OLT outcomes. Results:, Patients undergoing OLT in the post-MELD era had more severe liver disease at the time of transplantation (mean MELD = 20.5) vs. those in the pre-MELD era (mean MELD = 17.0). There were no differences in the unadjusted patient or graft survival at 1 year post-OLT. This difference remained insignificant after adjusting for a range of prespecified recipient, donor, and transplant centre-related factors in multivariable survival analysis. Conclusions:, Although liver disease severity is higher in the post- vs. pre-MELD era, there has been no change in long-term post-OLT patient or graft survival. These results indicate that the MELD era has achieved its primary goals by allocating cadaveric livers to the sickest patients without compromising post-OLT survival. [source]

    Single nucleotide insertion in the 5,-untranslated region of hepatitis C virus with clearance of the viral RNA in a liver transplant recipient during acute hepatitis B virus superinfection

    Consolato Sergi
    Abstract: Hepatitis C virus (HCV) infection is an important etiology in patients undergoing orthotopic liver transplantation (OLT) world-wide. Antiviral therapy-related clearance of HCV RNA may occur both in patients with chronic HCV infection and in transplanted patients for HCV-related liver cirrhosis, but the role of the 5,-untranslated region (UTR) of HCV containing the internal ribosome entry site (IRES), which directs the translation of the viral open reading frame has not hitherto been evaluated. We studied the 5,-UTR in an HCV-infected recipient of a liver graft that showed spontaneous clearance of HCV RNA during an acute hepatitis B virus (HBV) superinfection. Sequencing of the 5,-UTR of HCV showed a nucleotide A insertion at position 193 of the IRES. [source]

    Seventh Day Syndrome , acute hepatocyte apoptosis associated with a unique syndrome of graft loss following liver transplantation,

    Muhammed Ashraf Memon
    Abstract:Aim: The aim of this study is to describe a unique 7th day syndrome (7DS), quite different from other causes of post-transplantation allograft dysfunction in a group of orthotopic liver transplant (OLT) patients who needed retransplantation. Methods: A retrospective analysis of 594 consecutive OLT over an 8-year period revealed that 10 patients developed allograft dysfunction approximately 7 days following an initially normal graft function. Results: The features included: (a) severe liver failure; (b) sudden peak of extremely high liver enzymes at approximately day 7; (c) serial liver biopsy findings of central lobular hemorrhage with minimal inflammatory cell infiltrate and (d) an explant with no evidence of vascular thrombosis. The biochemical and morphometric pathological data of these patients were compared with data of patitents who had early acute rejection (AR), hepatic artery thrombosis (HAT), primary non-function (PNF), severe sepsis and no dysfunction. Lastly, serial liver core biopsies and explants were tested for evidence of apoptosis, which revealed a significantly higher number of apoptotic hepatocytes in 7DS compared to all control groups. Conclusions: Seventh Day Syndrome is a distinct entity associated with early graft dysfunction characterized by a marked apoptosis of hepatocytes. Fas receptor activation or other pathways of program cell death may be implicated in occurrence of 7DS. [source]

    Liver transplantation for non,hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literature

    Eric J. Grossman
    Orthotopic liver transplantation (OLT) is currently incorporated into the treatment regimens for specific nonhepatocellular malignancies. For patients suffering from early-stage, unresectable hilar cholangiocarcinoma (CCA), OLT preceded by neoadjuvant radiotherapy has the potential to readily achieve a tumor-free margin, accomplish a radical resection, and treat underlying primary sclerosing cholangitis when present. In highly selected stage I and II patients with CCA, the 5-year survival rate is 80%. As additional data are accrued, OLT with neoadjuvant chemoradiation may become a viable alternative to resection for patients with localized, node-negative hilar CCA. Hepatic involvement from neuroendocrine tumors can be treated with OLT when metastases are unresectable or for palliation of medically uncontrollable symptoms. Five-year survival rates as high as 90% have been reported, and the Ki67 labeling index can be used to predict outcomes after OLT. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin. The data from single-institution series are limited, but compiled reviews have reported 1- and 10-year survival rates of 96% and 72%, respectively. Hepatoblastoma is the most common primary hepatic malignancy in children. There exist subtle differences in the timing of chemotherapy between US and European centers; however, the long-term survival rate after transplantation ranges from 66% to 77%. Fibrolamellar hepatocellular carcinoma is a distinct liver malignancy best treated by surgical resection. However, there is an increasing amount of data supporting OLT when resection is contraindicated. In the treatment of either primary or metastatic hepatic sarcomas, unacceptable survival and recurrence rates currently prohibit the use of OLT. Liver Transpl 16:930-942, 2010. 2010 AASLD. [source]

    Comparison of calibrated and uncalibrated arterial pressure,based cardiac output monitors during orthotopic liver transplantation,

    Vladimir Krejci
    Arterial pressure,based cardiac output monitors (APCOs) are increasingly used as alternatives to thermodilution. Validation of these evolving technologies in high-risk surgery is still ongoing. In liver transplantation, FloTrac-Vigileo (Edwards Lifesciences) has limited correlation with thermodilution, whereas LiDCO Plus (LiDCO Ltd.) has not been tested intraoperatively. Our goal was to directly compare the 2 proprietary APCO algorithms as alternatives to pulmonary artery catheter thermodilution in orthotopic liver transplantation (OLT). The cardiac index (CI) was measured simultaneously in 20 OLT patients at prospectively defined surgical landmarks with the LiDCO Plus monitor (CIL) and the FloTrac-Vigileo monitor (CIV). LiDCO Plus was calibrated according to the manufacturer's instructions. FloTrac-Vigileo did not require calibration. The reference CI was derived from pulmonary artery catheter intermittent thermodilution (CITD). CIV -CITD bias ranged from ,1.38 (95% confidence interval = ,2.02 to ,0.75 L/minute/m2, P = 0.02) to ,2.51 L/minute/m2 (95% confidence interval = ,3.36 to ,1.65 L/minute/m2, P < 0.001), and CIL -CITD bias ranged from ,0.65 (95% confidence interval = ,1.29 to ,0.01 L/minute/m2, P = 0.047) to ,1.48 L/minute/m2 (95% confidence interval = ,2.37 to ,0.60 L/minute/m2, P < 0.01). For both APCOs, bias to CITD was correlated with the systemic vascular resistance index, with a stronger dependence for FloTrac-Vigileo. The capability of the APCOs for tracking changes in CITD was assessed with a 4-quadrant plot for directional changes and with receiver operating characteristic curves for specificity and sensitivity. The performance of both APCOs was poor in detecting increases and fair in detecting decreases in CITD. In conclusion, the calibrated and uncalibrated APCOs perform differently during OLT. Although the calibrated APCO is less influenced by changes in the systemic vascular resistance, neither device can be used interchangeably with thermodilution to monitor cardiac output during liver transplantation. Liver Transpl 16:773-782, 2010. 2010 AASLD. [source]

    Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen,positive patients after liver transplantation

    Sammy Saab
    Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P = 0.031 and P < 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P < 0.001) and post-OLT chemotherapy (P , 0.001). The 3- and 5-year survival rates were significantly decreased in patients with HBV reinfection (P = 0.007) and in patients with HCC recurrence after OLT (P = 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence. Liver Transpl 15:1525,1534, 2009. 2009 AASLD. [source]

    Postreperfusion syndrome during liver transplantation for cirrhosis: Outcome and predictors

    Catherine Paugam-Burtz
    During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3-year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living-donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07-1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis. Liver Transpl 15:522,529, 2009. 2009 AASLD. [source]

    Impact of preoperative overt hepatic encephalopathy on neurocognitive function after liver transplantation,,

    Eva U. Sotil
    In the current Model for End-Stage Liver Disease allocation system, patients are at risk of suffering repeated episodes of hepatic encephalopathy (HE) while waiting for an orthotopic liver transplantation (OLT); the posttransplantation impact of these episodes has not been well explored. We evaluated the cognitive function and quality of life in a group of OLT recipients (n = 25) who had suffered from overt HE prior to their procedure (HE-PreLT group) and compared their performance to that of a similar group of patients (n = 14) without overt HE (No HE-PreLT group) as well as to controls. Patients were selected from a cohort of 280 patients who underwent OLT during this period; the presence of clinical confounders excluded many of the remaining subjects. Demographic and clinical characteristics were balanced among groups. At an average of 18 months after OLT, we administered 2 neuropsychological batteries [Psychometric Hepatic Encephalopathy Score (PHES) test battery and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]; a pyschophysiological test (critical flicker frequency); and the SF-36 quality of life score. The HE-PreLT group scored below controls in 5 of 6 cognitive domains tested by RBANS, 3 of 6 PHES subtests, as well as the critical flicker frequency test. The No HE-PreLT group scored below the controls in 1 of the 6 cognitive domains tested by RBANS. The more severe neurocognitive abnormalities seen in the HE-PreLT group did not appear to affect quality of life, as lower values than normative data were only found in 1 of the 8 SF-36 scales. In conclusion, neurocognitive abnormalities were more severe in liver transplant recipients that had suffered from overt HE prior to OLT. Prospective studies of neurocognitive function pre-OLT and post-OLT are needed to fully determine the impact of such abnormalities. Liver Transpl 15:184,192, 2009. 2009 AASLD. [source]

    Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma

    Mauricio Silva
    Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden , 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL) from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had tumors within and beyond the MC were compared. The survival analysis was done (1) with the intention-to-treat principle and (2) among transplanted patients. A total of 281 patients were included in WL. Twenty-four cases did not undergo OLT (a dropout rate of 8.5%); all but 1 case had tumors within the MC. Of the 257 transplanted patients, 26 had tumors beyond the MC in the pre-OLT evaluation. Based on the intention-to-treat analysis, the 5-year survival was 56% versus 66% in patients who had tumors within and beyond the MC, respectively (P = 0.487). Among transplanted patients, the 5-year survival was 62% versus 69%, respectively (P = 0.734). Through multivariate analysis, microvascular invasion was an independent prognostic factor of poor survival (P = 0.004). The recurrence probabilities at 1 and 5 years were 7% versus 12% and 14% versus 28% in patients with tumors within and beyond the MC, respectively (P = 0.063). The multivariate analysis demonstrated that both poorly differentiated tumors (P < 0.001) and microvascular invasion (P < 0.001) increased the risk of recurrence. The expansion to up to 3 nodules, each up to 5 cm, and a cumulative tumor burden , 10 cm did not result in a reduction of survival in comparison with patients who had tumors within the MC. Liver Transpl 14:1449,1460, 2008. 2008 AASLD. [source]

    Effect of hospital volume and teaching status on outcomes of acute liver failure

    Ashwin N. Ananthakrishnan
    Acute liver failure (ALF) often requires multidisciplinary support. Higher hospital volumes have been associated with better outcomes for surgical procedures, but whether such a relationship exists for ALF has not been explored previously. In this study, our aim was to examine if hospital volume affects mortality from ALF. Using data from the Nationwide Inpatient Sample for the years 2001 to 2004, we identified cases by the presence of a primary discharge diagnosis of ALF (International Classification of Diseases, 9th revision, Clinical Modification code 570.x). Hospitals were divided into low-, medium-, and high-volume hospitals on the basis of 1 to 5, 6 to 20, and more than 20 annual ALF discharges. There were 17,361, 6756, and 1790 discharges with ALF from low-, medium-, and high-volume hospitals, respectively. There was no difference in adjusted mortality between low- and high-volume hospitals (odds ratio 0.94, 95% confidence interval 0.68-1.28). Teaching hospitals had a trend toward lower mortality among patients with hepatic encephalopathy (odds ratio 0.69, 95% confidence interval 0.47-1.01). High-volume centers had a higher rate of orthotopic liver transplantation (OLT) primarily because they were transplant centers, had better in-hospital post-OLT survival, and showed a trend toward a shorter time to OLT. In conclusion, patients with ALF receiving care at teaching hospitals and high-volume centers tend to be sicker. However, teaching hospitals and high-volume centers have equivalent in-hospital survival despite caring for this more severely ill cohort. Liver Transpl 14:1347,1356, 2008. 2008 AASLD. [source]

    Analysis of recent pediatric orthotopic liver transplantation outcomes indicates that allograft type is no longer a predictor of survivals,

    Natasha S. Becker
    Two strategies to increase the donor allograft pool for pediatric orthotopic liver transplantation (OLT) are deceased donor segmental liver transplantation (DDSLT) and living donor liver transplantation (LDLT). The purpose of this study is to evaluate outcomes after use of these alternative allograft types. Data on all OLT recipients between February 2002 and December 2004 less than 12 years of age were obtained from the United Network for Organ Sharing database. The impact of allograft type on posttransplant survivals was assessed. The number of recipients was 1260. Of these, 52% underwent whole liver transplantation (WLT), 33% underwent DDSLT, and 15% underwent LDLT. There was no difference in retransplantation rates. Immediate posttransplant survivals differed, with WLT patients having improved 30-day patient survivals compared to DDSLT and LDLT patients (P = 0.004). Although unadjusted 1-year patient survivals were better for WLT versus DDSLT (P = 0.01), after risk adjustment, 1-year patient survivals for WLT (94%), DDSLT (91%), and LDLT (93%) were similar (P values > 0.05). Unadjusted allograft survivals were better for WLT and LDLT in comparison with DDSLT (P = 0.009 and 0.018, respectively); however, after adjustment, these differences became nonsignificant (all P values > 0.05). For patients , 2 years of age (n = 833), the adjusted 1-year patient and allograft survivals were also similar (all P values > 0.05). In conclusion, in the current era of pediatric liver transplantation, WLT recipients have better immediate postoperative survivals. By 1 year, adjusted patient and allograft survivals are similar, regardless of the allograft type. Liver Transpl 14:1125,1132, 2008. 2008 AASLD. [source]

    The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury

    Constantino Fondevila
    Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(,) rats were harvested, stored for 24 hours at 4C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+),C6(+), (2) C6(+),C6(,), (3) C6(,),C6(+), and (4) C6(,),C6(,). At day +1, C6(,) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 0.9, 7.3 1.3, 4.5 0.6, and 4.8 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(,) grafts (serum glutamic oxaloacetic transaminase: 2573 488, 1808 302, 1170 111, and 1188 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(,) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-,, interleukin-1,, and tumor necrosis factor messenger RNA/protein was also reduced in C6(,) OLTs in comparison with C6(+) OLTs. Western blot,assisted expression of proapoptotic caspase-3 was decreased in C6(,) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(,) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase,mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(,) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. Liver Transpl 14:1133,1141, 2008. 2008 AASLD. [source]

    Low recurrence of preexisting extrahepatic malignancies after liver transplantation

    Daniel Benten
    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. Liver Transpl, 2008. 2008 AASLD [source]

    Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma

    Michael A. Zimmerman
    Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy. Liver Transpl 2008. 2008 AASLD. [source]

    Frequency and predictors of de novo hepatocellular carcinoma in patients awaiting orthotopic liver transplantation during the model for end-stage liver disease era,

    Carla W. Brady
    In the current system of allocation, patients awaiting orthotopic liver transplantation (OLT) remain at risk of developing de novo hepatocellular carcinoma (HCC) and removal from the waiting list. Using the United Network for Organ Sharing database, we calculated the rate and identified predictors of de novo HCC in patients listed for OLT between February 2002 and December 2004. Among 8566 patients, 1167 (13.6%) developed de novo HCC. Predictors of increased odds of de novo HCC were older age, male gender, Asian race, other race, hepatitis C, and hepatitis B. A sensitivity analysis of 2067 patients waiting at least 6 months found that 16.2% developed de novo HCC. Older age [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.03, 1.07], male gender (OR 2.01; 95% CI 1.49, 2.71), Asian race (OR 2.39; 95% CI 1.20, 4.76), other race (OR 1.94; 95% CI 1.40, 2.68), hepatitis C (OR 2.36; 95% CI 1.76, 3.16), and hepatitis B (OR 1.96; 95% CI 1.19, 3.23) remained predictors of increased odds of de novo HCC, and alcoholic liver disease (OR 1.40; 95% CI 1.06, 1.86) emerged as a predictor of increased odds of de novo HCC. A significant proportion of patients listed for OLT develop de novo HCC. Identifying predictors of HCC in these patients may facilitate timely HCC screening and diagnosis. Liver Transpl 14:228,234, 2008. 2008 AASLD. [source]

    Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation

    Brian M. Parker
    Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (,0.02, 0.07) with P = 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (>12 ng/mL), P = 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT. Liver Transpl 14:46,52, 2008. 2007 AASLD. [source]

    Venous outflow obstruction in liver transplantation is associated with the anastomotic technique

    James D. Perkins M.D. Special Editor
    The outflow venovenous anastomosis represent a crucial aspect during orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation. The modified Belghiti liver hanging maneuver applied to the last phase of hepatectomy, lifting the liver, provides a better exposure of the suprahepatic region and allows easier orthogonal clamping of the three suprahepatic veins with a minimal portion of IVC occlusion. The outflow anastomosis constructed with a common cloacae of the three native suprahepatic veins is associated with a lower incidence of graft related venous outflow complications. The procedure planned in 120 consecutive OLT was achieved in 118 (99%). The outflow anastomosis was constructed on the common cloaca of the three hepatic veins in 111/120 cases (92.5%). No major complications were observed (bleeding during tunnel creation, graft outflow dysfunction, etc) except in one patient with acute Budd-Chiari, who successfully underwent retransplantation. [source]

    Recurrent hepatic lymphangiomatosis after orthotopic liver transplantation

    Seong H. Ra
    Hepatic lymphangiomatosis is a rare disease characterized by an abnormal lymphatic proliferation involving the liver alone, liver and spleen, or multiple organs. Hepatic lymphangiomatosis becomes symptomatic secondary to compression or replacement of the normal parenchyma, which can lead to liver failure. Resection and orthotopic liver transplantation (OLT) can be used as treatment for this disease. We herein describe a 42-year-old female who had undergone successful OLT for hepatic lymphangiomatosis with recurrent disease detected 19 yr later in the transplanted liver. This is, to our knowledge, the first described case of recurrent hepatic lymphangiomatosis after OLT. In conclusion, we discuss the clinical, radiologic, pathologic, and immunohistochemical findings and review other reported cases of hepatic lymphangiomatosis that have undergone OLT. Liver Transpl 13:1593,1597, 2007. 2007 AASLD. [source]

    Cost-effectiveness of screening for hepatopulmonary syndrome in liver transplant candidates,

    D. Neil Roberts
    The hepatopulmonary syndrome (HPS) is present in 15,20% of patients with cirrhosis undergoing orthotopic liver transplantation (OLT) evaluation. Both preoperative and post-OLT mortality is increased in HPS patients particularly when hypoxemia is severe. Screening for HPS could enhance detection of OLT candidates with sufficient hypoxemia to merit higher priority for transplant and thereby decrease mortality. However, the cost-effectiveness of such an approach has not been assessed. Our objective was to perform a cost-effectiveness analysis from a third-party payer's perspective of screening for HPS in liver OLT candidates. The costs and outcomes of 3 different strategies were compared: (1) no screening, (2) screening patients with a validated dyspnea questionnaire, and (3) screening all patients with pulse oximetry. Arterial blood gas analyses and contrast echocardiography were performed in patients with dyspnea or a pulse oximetry (SpO2) ,97% to define the presence of HPS. A Markov model was constructed simulating the natural history of cirrhosis in a cohort of patients 50 years old over a time horizon of their remaining life expectancy. Transition probabilities were obtained from published data available through Medline and U.S. vital statistics. Costs represented Medicare reimbursement data at our institution. Costs and health effects were discounted at a 3% annual rate. No screening was associated with a total cost of $291,898 and a life expectancy of 11.131 years. Screening with pulse oximetry was associated with a cost of $299,719 and a life expectancy of 12.27 years. Screening patients with the dyspnea-fatigue index was associated with a cost and life expectancy of $300,278 and 12.28 years, respectively. The incremental cost-effectiveness ratio of screening with pulse oximetry (compared to no screening) was $6,867 per life year gained, whereas that of the dyspnea-fatigue index (compared to pulse oximetry) was $55,900 per life year gained. The cost-effectiveness of screening depended on the prevalence and severity of HPS, and the choice of screening strategy was dependent on the sensitivity of the screening modality. In conclusion, screening for HPS, especially with pulse oximetry, is a cost-effective strategy that improves survival in transplant candidates predominantly by targeting the transplant to the subgroup of patients most likely to benefit. The utility of screening depends on the prevalence and severity of HPS in the target population. Liver Transpl, 2006. 2006 AASLD. [source]

    Cystatin C as a marker of renal function immediately after liver transplantation

    Gianni Biancofiore
    To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (SCyst), serum creatinine (Scr), and creatinine clearance (Ccr) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, SCyst and Scr was measured in simultaneously drawn blood samples, whereas Ccr was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/SCyst and I-GFR was stronger than that of 1/Scr or Ccr (P< 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m), Scr remained within the normal range, whereas the increase in Scyst was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m), Scr increased slightly, whereas Scyst was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were ,30% lower than that recorded on the first postoperative day, SCyst(P< 0.0001) and Scr (P< 0.01) levels were increased, whereas Ccr remained unchanged (P= 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of Scyst was better than that of Scr and Ccr. Scyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR. Liver Transpl 12:285,291, 2006. 2006 AASLD. [source]

    High preoperative recipient plasma 7,-hydroxycholesterol is associated with initial poor graft function after liver transplantation

    Stefano Ginanni Corradini
    Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the source,hepatic or extra-hepatic,of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7,-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7,-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n = 9) compared with those with initial good graft function (IGGF; n = 23) [mean SD: 30.63 26.42 and 11.57 15.76 ng/mL, respectively] (P = 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7,-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028). Patients with cirrhosis (n = 32) had increased oxysterol plasma levels compared with healthy controls (n = 49); livers with cirrhosis (n = 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n = 19). Oxysterols persisted elevated in plasma 1 month after OLT (n = 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT. (Liver Transpl 2005.) [source]

    A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation,

    Francis Y. Yao
    In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and ,8 cm, 2 or 3 lesions at least 1 >3 cm but ,5 cm with total tumor diameter of ,8 cm, or 4 or 5 nodules all ,3 cm with total tumor diameter ,8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT. (Liver Transpl 2005;11:1505,1514.) [source]

    Liver transplantation for Wilson's disease: The burden of neurological and psychiatric disorders

    Valentina Medici
    A retrospective data analysis on liver transplantation for Wilson's disease (WD) was performed among Italian Liver Transplant Centers. Thirty-seven cases were identified. The main indication for liver transplantation was chronic advanced liver disease in 78% of patients. Mixed hepatic and neuropsychiatric symptoms were recorded in 32.3%. Eight patients presented with fulminant liver failure; 44.8% were on medical treatment. Patient and graft survival at 3 months, 12 months, 3 years, 5 years, and 10 years after transplantation were, respectively, 91.8%, 89.1%, 82.9%, 75.6%, and 58.8%, and 85.3%, 83.0%, 77.1%, 70.3%, and 47.2%. Neurological symptoms significantly improved after orthotopic liver transplantation (OLT), but the survival of patients with mixed hepatic and neuropsychiatric involvement was significantly lower than in patients with liver disease alone (P = 0.04). WD characterized by hepatic involvement alone is a rare but good indication for liver transplantation when specific medical therapy fails. Patients with neuropsychiatric signs have a significantly shorter survival even though liver transplantation has a positive impact on neurological symptoms. In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment. (Liver Transpl 2005;11:1056,1063.) [source]