Juan G Abraldes

University of Alberta, Edmonton, Alberta, Canada

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Publications (154)966 Total impact

  • Juan G. Abraldes, Puneeta Tandon, Jason Yap
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    Clinical Liver Disease. 10/2014; 4(4).
  • Juan G Abraldes, Puneeta Tandon
    Hepatology 10/2014; · 12.00 Impact Factor
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    ABSTRACT: Whether pre-operative clinically significant portal hypertension (CSPH) has or not an impact on the outcome of surgery for hepatocellular carcinoma (HCC) in patients with compensated cirrhosis is debated. This systematic review assesses the impact of CSPH on the outcome of HCC in patients with compensated cirrhosis treated with surgery.We performed a systematic search of the MEDLINE database (articles published in full in English language from 1996 to October 2013) and related bibliography for studies reporting on the postoperative outcomes (3- and 5-year mortality and/or early clinical decompensation) of patients with HCC and compensated cirrhosis treated with surgery according to the presence or absence of CSPH. Independent extraction of articles by two authors using predefined data fields, including study quality indicators was used; pooled analyses were based on random-effects models.Eleven studies in total met our inclusion criteria (eight studies for 3- and 5-year postoperative mortality and 8 studies for postoperative clinical decompensation). Moderate heterogeneity among studies for both outcomes was observed, which disappeared after pooling studies using similar methods to assess CSPH. The presence of CSPH increased the risk of 3- and 5-year mortality vs. absence of CSPH: pooled odds ratio (OR) for 3-year mortality: 2.09; 95% confidence interval [CI], 1.52-2.88; for 5-year mortality: 2.07; 95% CI, 1.51-2.84. CSPH also increased the risk of postoperative clinical decompensation (pooled OR: 3.04; 95% CI, 2.02-4.59). Conclusions: CSPH (evaluated by any method) significantly increases the risk of 3- and 5-year mortality and of clinical decompensation after surgery for HCC. (Hepatology 2014;)
    Hepatology 09/2014; · 12.00 Impact Factor
  • Juan G. Abraldes, Philippe Sarlieve, Puneeta Tandon
    Clinics in Liver Disease 08/2014; · 2.82 Impact Factor
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    ABSTRACT: Patients with cirrhosis have reduced exercise tolerance, measured objectively as decreased peak exercise oxygen uptake (peak VO2). Reduced peak VO2 is associated with decreased survival time. The effect of aerobic exercise training on peak VO2 has not been well studied in patients with cirrhosis. We evaluated the safety and efficacy of 8 weeks of supervised exercise on peak VO2, quadriceps muscle thickness, and quality of life. In a prospective pilot study, stable patients (79% male, 57.6±6.7 years old) with Child Pugh class A or B cirrhosis (mean model for end-stage liver disease [MELD]score, 10±2.2) were randomly assigned to groups that received exercise training (n=9) or usual care (controls, n=10) at the University of Alberta Hospital in Canada, from February through June 2013. Supervised exercise was performed on a cycle ergometer 3 days/week for 8 weeks at 60% to 80% of baseline peak VO2. Peak VO2, quadriceps muscle thickness (measured by ultrasound), thigh circumference, answers from chronic liver disease questionnaires (CLDQs), EQ-visual analog scores (VAS), 6-minute walk distance, and MELD scores were evaluated at baseline and at week 8. Analysis of covariance was used to compare variables. At week 8, peak VO2 was 5.3 ml/kg/min higher exercise group compared with controls (95% confidence interval, 2.9-7.8; P=.001). Thigh circumference (P=.001), thigh muscle thickness (P=.01), and EQ-VAS determined self-perceived health status (P=.01) were also significantly higher in the exercise group compared with controls at week 8; fatigue subscores of the CLDQ were lower in the exercise group compared with controls (P=.01). No adverse events occurred during cardiopulmonary exercise testing or training. In a controlled prospective pilot trial, 8 weeks of supervised aerobic exercise training increased peak VO2 and muscle mass and reduced fatigue in patients with cirrhosis. No relevant adverse effects were observed. Larger trials are needed to evaluate the effects of exercise in patients with cirrhosis. Clinicaltrials.gov number, NCT01799785.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 04/2014; · 5.64 Impact Factor
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    ABSTRACT: Background Understanding patients’ attitudes to clinical experiences is essential for developing high-quality patient-centred health-care, since a better knowledge of patients’ tolerance and satisfaction might allow implementing measures that ameliorate comfort, care and use of resources.AimsWe aimed to describe patients’ tolerance and satisfaction to invasive hepatic hemodynamic procedures, and to investigate which factors might influence patients’ perspective in this field.Methods Visual Analogue Scale (VAS) questionnaires regarding pain and duration (for tolerance), and comfort and general handling (for satisfaction) were prospectively administered to all consecutive patients (N=327) submitted to hepatic hemodynamic procedures (N=355) in a tertiary care setting during 2011. VAS scores ranged between 0 and 100 mm and items were defined as excellent if <10 mm; good if 10-20 mm and inadequate if >20 mm. Clinical and laboratory data were also collected.ResultsSatisfaction was excellent in >95% of cases (mean 2±5 mm, median 0 mm) and average tolerance was good (15±18 mm; median 6 mm). 59% of patients had excellent tolerance, 9% good and 32% had inadequate tolerance. Duration and complexity of the procedure and limited operator's experience were associated with inadequate tolerance on univariate analysis; duration of the procedure remained the only independent factor associated with inadequate tolerance on multivariate analysis. Procedures lasting <35 minutes had a >80% probability of being well tolerated.Conclusions Satisfaction and tolerance to hepatic hemodynamic procedures are excellent and good, respectively. Tolerance was decreased in long procedures; hence reducing as much as possible the duration of the procedures might further improve tolerance.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 03/2014; · 3.87 Impact Factor
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    ABSTRACT: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90 day) mortality. We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 through January 2008 with features of AH, and developed a histologic scoring system to determine risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the US and Europe, and a semi-quantitative scoring system was developed, called the alcoholic hepatitis histologic score (AHHS). The system was validated in an independent set of 109 patients. Inter-observer agreement was evaluated by weighted κ statistic analysis. Degree of fibrosis, neutrophil infiltration, type of bilirubinostasis, and presence mega-mitochondria were independently associated with 90 day mortality. We used these 4 parameters to develop the AHHS to identify patients with low (0-3 points), moderate (4-5 points), and high (6-9 points) risks of death within 90 days (3%, 19%, and 51%, respectively; P<.0001). The AHHS estimated 90 day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Inter-rate agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. We identified histologic features associated with severity of AH and developed a patient classification system that might be used in clinical decision making.
    Gastroenterology 01/2014; · 12.82 Impact Factor
  • Annals of surgery 11/2013; · 7.90 Impact Factor
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    ABSTRACT: Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality (15-20%). Previously described models are seldom used to determine prognoses of these patients, partially because they have not been externally validated and because they include subjective variables, such as bleeding during endoscopy and Child-Pugh score, which are inconsistently evaluated. We aimed to improve determination of risk for patients with AVB. We analyzed data collected from 178 patients with cirrhosis (Child-Pugh scores of A, B, and C: 15%, 57%, and 28%) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n=240) and Spain (n=221). Among study subjects, 6-week mortality was 16%. MELD was the best model in terms of discrimination; it was re-calibrated to predict 6-week mortality with logistic regression (logit, -5.312+0.207•MELD; bootstrapped R2, 0.3295). MELD values ≥19 predicted ≥20% mortality, whereas a MELD scores <11 predicted <5% mortality. The model performed well for patients from Canada, at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.
    Gastroenterology 10/2013; · 12.82 Impact Factor
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    ABSTRACT: Adult living-donor liver transplantation recipients undergo important hemodynamic changes during the procedure, which in turn have proven to be of the upmost importance when dealing with small grafts, to avoid the so-called "small-for-size" syndrome. Back in 2003, we started a hemodynamic monitoring protocol in adult living-donor liver transplantation recipients, which evaluated the hemodynamic status of the patient 24 hr before, during, and 3 days after transplantation. We analyzed the correlation between the same hemodynamic variables measured in the hemodynamic laboratory and those taken in the operating room. With the exception of cardiac index and indexed systemic vascular resistance, all the other hepatic and systemic hemodynamic parameters measured before and during the intervention, as well as during and after the intervention, showed a lack of correlation. The observed lack of correlation may happen due to many factors, such as the influence of vasoactive and anesthetic drugs, total muscular relaxation, or the presence of an open abdomen. As a result, a direct comparison between hemodynamic values should only be done when measured in the same conditions.
    Transplantation 10/2013; · 3.78 Impact Factor
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    ABSTRACT: Outcome of variceal bleeding (VB) in patients with hepatocellular carcinoma (HCC) is unknown. We compared outcomes after VB in patients with and without HCC. All patients with HCC and esophageal VB admitted between 2007-2010 were included. Follow up was prolonged until death, transplantation or 06.2011. For each HCC-patient, a patient without HCC matched by age and Child class was selected. 292 patients were included, 146 HCC (BCLC class 0-3 patients, A-25, B-29, C-45, D-41) and 146 without HCC. No differences were observed regarding prior use of prophylaxis, clinical presentation, endoscopic findings, and initial endoscopic treatment. 5-day failure was similar (25% in HCC vs 18% in non-HCC, p=0.257). HCC patients had greater 6-week rebleeding rate (16 vs 7%, respectively, p=0.025) and 6-week mortality (30% vs 15%, p=0.003). Fewer patients with HCC received secondary prophylaxis after bleeding (77% vs 89%, p=0.009) and standard combination therapy was used less frequently (58% vs 70%, p=0.079). Secondary prophylaxis failure was more frequent (50% vs 31%, p=0.001) and survival significantly shorter in patients with HCC (median survival: 5 months Vs greater than 38 months in patients without HCC; p<0.001). Lack of prophylaxis increased rebleeding and mortality. On multivariate analysis Child score, presence of HCC, portal vein thrombosis and lack of secondary prophylaxis were predictors of death. Conclusions: Patients with HCC and variceal bleeding have worse prognosis than patients with variceal bleeding without HCC. Secondary prophylaxis offers survival benefit in HCC patients. (Hepatology 2013;).
    Hepatology 07/2013; · 12.00 Impact Factor
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    ABSTRACT: Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 week. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavalability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability, and decreased O2- levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. Conclusion: The present study shows that blockade of the leptin signalling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.
    AJP Gastrointestinal and Liver Physiology 07/2013; · 3.65 Impact Factor
  • Annalisa Berzigotti, Juan G Abraldes
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    ABSTRACT: Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article.
    Gastroenterología y Hepatología 05/2013; · 0.57 Impact Factor
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    ABSTRACT: We identified in the transcriptome analysis of patients with alcoholic hepatitis (AH) osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, Western blotting and ELISA. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPN(-/-) mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH compared to normal livers and other types of chronic liver diseases and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and MMP-7) and cleaved-OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C SNP of the OPN gene compared to patients with alcohol abuse without liver disease. Importantly, OPN(-/-) mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by LPS and stimulated inflammatory actions in hepatic stellate cells. Conclusion: Human and experimental data suggest a role for OPN in the pathogenesis of AH. Further studies should evaluate OPN as a potential therapeutic target. (HEPATOLOGY 2013.).
    Hepatology 05/2013; · 12.00 Impact Factor
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    Annalisa Berzigotti, Juan G Abraldes, Jaume Bosch
    Hepatology 05/2013; · 12.00 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Measurement of the hepatic venous pressure gradient (HVPG) offers valuable prognostic information in patients with cirrhosis. In specific circumstances, (children, agitated patients, TIPS placement) deep sedation is required. This study aims to assess the impact of deep sedation on the accuracy of hepatic/portal pressure measurements. METHODS: Forty-four patients were included. Measurements of baseline HVPG (n = 30), HVPG response to i.v. propranolol (n = 11), portal pressure gradient (PPG) after TIPS (n = 27) and of cardio-pulmonary pressures (n = 25) were obtained in awake conditions and under deep sedation with propofol and remifentanil. RESULTS: During deep sedation, a marked oscillation within respiratory cycle was observed in abdominal pressures. End-expiratory sedated HVPG showed a better agreement with awake HVPG (intra-class correlation coefficient - ICC 0.864) than end-inspiratory HVPG (ICC 0.796). However, in almost half of the patients both values differed by more than 10%. Accuracy was not improved by using mean HVPG along the respiratory cycle. Similarly, changes in HVPG caused by propranolol while under sedation had a poor agreement to those obtained in awake conditions. Indeed, about a half of patients were misclassified according to the 10% HVPG reduction target. After TIPS, PPG values obtained under sedation were significantly different to awake PPG, usually underestimating the awake value. The systemic hemodynamic changes induced by sedation were not associated to a greater variability of PPG/HVPG measurements. CONCLUSION: Deep sedation with propofol and remifentanil adds substantial variability and uncertainty to HVPG/PPG measurements. This must be considered when using these values to estimate prognosis, or targeting HVPG/PPG reductions.
    Liver international: official journal of the International Association for the Study of the Liver 05/2013; · 3.87 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Hepatic blood flow (HBF) is best estimated by Fick's method during indocyanine green constant infusion (ICG-HBF) on hepatic vein catheterization. We investigated the consistency and agreement of HBF measured by Doppler ultrasound (US-HBF) as compared with ICG-HBF in portal hypertensive patients with cirrhosis. METHODS: In 50 patients observed for HVPG measurement (56% compensated; Child score 7±2; HVPG 16.6±6.0 mmHg; varices in 75%) US-HBF (Sequoia-512-Acuson; 4.5-7 MHz convex probe; US-HBF= hepatic artery blood flow + portal vein blood flow) and ICG-HBF (Fick's method after an equilibration period of at least 45 minutes of ICG bolus of 5 mg + constant rate infusion of 0.2 mg/min). Intraclass correlation coefficient (ICC) for consistency and absolute agreement between US-HBF and ICG-HBF were calculated. RESULTS: Mean ICG-HBF and US-HBF were similar, being respectively 1004±543 ml/min, and 994±494 ml/min (p=0.661 vs. ICG-HBF). However, results in individual patients disclosed marked differences between the two methods (386±415 ml/min), and showed only moderate consistency (ICC 0.456; p<0.0001), absolute agreement (ICC 0.461; p<0.0001) and linear correlation (R=0.464; p<0.0001). The discrepancy between the two methods was maximal in patients with poor liver function, high HBF by any technique and more arterialized liver circulation. Hepatic artery blood flow ⩾40% of US-HBF indicated with 90% specificity a discrepancy ⩾20% between US-HBF and ICG-HBF. CONCLUSIONS: HBF estimations by Doppler-ultrasound and ICG are significantly correlated, but their discrepancy in individual cases is high. Estimation of HBF by Doppler-US should be considered unreliable in patients with poor hepatic function and large liver arterialization.
    Journal of Hepatology 05/2013; · 9.86 Impact Factor
  • Miguel Bruguera, Juan G. Abraldes
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    ABSTRACT: The present article aims to provide answers to questions frequently asked by physicians attending patients with Wilson's disease (WD) or those with a suspected diagnosis of WD. The article is divided into 2 parts: a first part with answers to questions relating to the diagnosis of this entity and a second with answers to questions concerning treatment. A brief appendix is included with responses to questions not falling into either of these 2 categories.
    Gastroenterología y Hepatología. 05/2013; 36(5):316–325.
  • Miguel Bruguera, Juan G Abraldes
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    ABSTRACT: The present article aims to provide answers to questions frequently asked by physicians attending patients with Wilson's disease (WD) or those with a suspected diagnosis of WD. The article is divided into 2 parts: a first part with answers to questions relating to the diagnosis of this entity and a second with answers to questions concerning treatment. A brief appendix is included with responses to questions not falling into either of these 2 categories.
    Gastroenterología y Hepatología 04/2013; · 0.57 Impact Factor
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    ABSTRACT: Lifelong immunosuppression increases morbidity and mortality in liver transplantation. Discontinuation of immunosuppressive drugs could lessen this burden, but the safety, applicability and clinical outcomes of this strategy need to be carefully defined. We enrolled 102 stable liver recipients at least 3 years after transplantation in a single-arm multi-center immunosuppression withdrawal trial. Drugs were gradually discontinued over a 6-9 month period. The primary end-point was the development of operational tolerance, defined as successful immunosuppressive drug cessation maintained for at least 12 months with stable graft function and no histopathologic evidences of rejection. Out of the 98 recipients evaluated, 57 rejected and 41 successfully discontinued all immunosuppressive drugs. In non-tolerant recipients rejection episodes were mild and resolved over 5.6 months (2 non-tolerant patients still exhibited mild gradually improving cholestasis at the end of follow-up). In tolerant recipients no progressive clinically-significant histological damage was apparent in follow-up protocol biopsies performed up to 3 years following drug withdrawal. Tolerance was independently associated with time since transplantation (OR 1.353; p = 0.0001), recipient age (OR 1.073; p = 0.009), and male gender (OR 4.657; p = 0.016). A predictive model incorporating the two first clinical variables identified subgroups of recipients with very high (79%), intermediate (30-38%), and very low (0%) likelihood of successful withdrawal. Conclusion: When conducted at late time points after transplantation, immunosuppression withdrawal is successful in a high proportion of carefully selected liver recipients. A combination of clinical parameters could be useful to predict the success of this strategy. Additional prospective studies are now needed to confirm these results and to validate clinically-applicable diagnostic biomarkers. (HEPATOLOGY 2013.).
    Hepatology 03/2013; · 12.00 Impact Factor

Publication Stats

3k Citations
966.00 Total Impact Points


  • 2014
    • University of Alberta
      • Division of Gastroenterology
      Edmonton, Alberta, Canada
  • 2010–2014
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
    • University College London
      Londinium, England, United Kingdom
  • 2013
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 2002–2013
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2000–2013
    • University of Barcelona
      • Departament de Medicina
      Barcelona, Catalonia, Spain
  • 2009
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 2008–2009
    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florence, Tuscany, Italy
    • Centro de Investigación Biomédica Esther Koplowitz
      Barcino, Catalonia, Spain
  • 2005
    • Yale University
      • Section of Digestive Diseases
      New Haven, CT, United States
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Hematology
      Firenzuola, Tuscany, Italy