Vicente Arroyo

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcino, Catalonia, Spain

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Publications (558)4723.56 Total impact

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    ABSTRACT: The peripheral arterial vasodilation hypothesis has been most influential in the field of cirrhosis and its complications. It has spawned hundreds of pathophysiogical studies in experimental and human cirrhosis and is the theoretical basis of life-saving treatments. It is undisputed that splanchnic arterial vasodilation contributes to portal hypertension and is the basis for manifestations such as ascites and hepatorenal syndrome, but the body of research generated by the hypothesis has revealed gaps in the original pathophysiological interpretation of these complications. The expansion of our knowledge on the mechanisms regulating vascular tone, inflammation and the host-microbiota interaction require a broader approach to advanced cirrhosis encompassing the whole spectrum of its manifestations. Indeed, multi-organ dysfunction and failure likely result from a complex interplay where the systemic spread of bacterial products represents the primary event. The consequent activation of the host innate immune response triggers endothelial molecular mechanisms responsible for arterial vasodilation, and also jeopardizes organ integrity with a storm of pro-inflammatory cytokines and reactive oxygen and nitrogen species. Thus, the picture of advanced cirrhosis could be seen as the result of an inflammatory syndrome in contradiction with a simple hemodynamic disturbance. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 07/2015; DOI:10.1016/j.jhep.2015.07.004 · 10.40 Impact Factor
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    PLoS ONE 06/2015; 10(6):e0128145. DOI:10.1371/journal.pone.0128145 · 3.23 Impact Factor
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    ABSTRACT: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis, organ failure(s) and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT), or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis (CANONIC) study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4% and worsened in 20.4%. The 28-day transplant-free mortality was low-moderate (6-18%) in patients with non-severe early course (final no ACLF or ACLF-1) and high-very high (42-92%) in patients with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score - (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥ 12 mg/dL) at ACLF diagnosis. Eighty one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short-(28-day) and mid-(90-day)term mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3 - 7 days, and did not undergo LT, mortality was 100% by 28 days Conclusions: The assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation due to futility. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 04/2015; DOI:10.1002/hep.27849 · 11.19 Impact Factor
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    ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. Study aim was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs. Prospective cohort study in a tertiary referral centre of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients. Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4±3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953±1,198 vs 83±79 μg/gr of creatinine, respectively, p=0.008). Moreover, 7 of the 11 patients with persistent AKI (64%) died within three months compared with only 1 of the 19 (5%) patients with transient AKI (p=0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of 3-month mortality was persistent AKI. Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 04/2015; DOI:10.1016/j.jhep.2015.04.004 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S373. DOI:10.1016/S0168-8278(15)30404-9 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S351-S352. DOI:10.1016/S0168-8278(15)30355-X · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S857-S858. DOI:10.1016/S0168-8278(15)31515-4 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S848. DOI:10.1016/S0168-8278(15)31495-1 · 10.40 Impact Factor
  • Vicente Arroyo · Richard Moreau · Rajiv Jalan · Pere Ginès
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    ABSTRACT: Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
    Journal of Hepatology 04/2015; 62(1S):S131-S143. DOI:10.1016/j.jhep.2014.11.045 · 10.40 Impact Factor
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    ABSTRACT: Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria. 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% vs. 3.8%, p<.001). The presence of SIRS was a major predictor of MOF (odds ratio 2.69, p=.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein (hsCRP), procalcitonin and lipopolysaccharide (LPS) at admission. All of them predicted mortality. Procalcitonin, but not hsCRP, serum levels identified those patients with SIRS and infection. LPS serum levels predicted MOF and the response to prednisolone. Conclusion: SIRS, in the presence or absence of infections, is a major determinant of MOF and mortality in AH. The mechanisms involved in the development of SIRS should be investigated. Procalcitonin serum levels can help identifying patients with infection. LPS levels may help predicting mortality and the response to steroids. This article is protected by copyright. All rights reserved.
    Hepatology 03/2015; DOI:10.1002/hep.27779 · 11.19 Impact Factor
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    ABSTRACT: Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 02/2015; DOI:10.1136/gutjnl-2014-307979 · 13.32 Impact Factor
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    ABSTRACT: Acute renal failure (ARF) is a common complication in patients with decompensated cirrhosis. The traditional diagnostic criteria of renal failure in these patients were proposed in 19961 and have been refined in subsequent years.2 According to these criteria, ARF is defined as an increase in serum creatinine (sCr) of ≥50% from baseline to a final value >1.5 mg/dL (133 µmol/L). However, the threshold value of 1.5 mg/dL (133 µmol/L) sCr to define renal failure in patients with decompensated cirrhosis has been challenged.3 ,4 In addition, the timeframe to distinguish acute from chronic renal failure has not been clearly identified, the only exception being type 1 hepatorenal syndrome (HRS). Meanwhile, new definitions for ARF, now termed acute kidney injury (AKI), have been proposed and validated in patients without cirrhosis.5-7 Recently these new criteria were also proposed and applied in the diagnosis of AKI in patients with cirrhosis.3 ,8-15 Thus, in December 2012, the International Club of Ascites (ICA) organised a consensus development meeting in Venice, Italy, in order to reach a new definition of AKI in patients with cirrhosis. The discussion among the experts continued thereafter for 2 years, both online and through several meetings, between those experts who had different positions on crucial points on the subject. This paper reports the scientific evidence supporting the final proposal of a new approach to the diagnosis and treatment of this condition, on which the experts agreed.
    Gut 01/2015; 64(4). DOI:10.1136/gutjnl-2014-308874 · 13.32 Impact Factor
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    Journal of Hepatology 01/2015; 23(4). DOI:10.1016/j.jhep.2014.12.029 · 10.40 Impact Factor
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    ABSTRACT: Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in a number of diseases that have inflammation as a common underlying cause. sEH limits tissue levels of cytochrome P450 (CYP) epoxides derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFA) by converting these antiinflammatory mediators into their less active diols. Here, we explored the metabolic effects of a sEH inhibitor (t-TUCB) in fat-1 mice with transgenic expression of an omega-3 desaturase capable of enriching tissues with endogenous omega-3 PUFA. These mice exhibited increased CYP1A1, CYP2E1, and CYP2U1 expression and abundant levels of the omega-3-derived epoxides 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic (19,20-EDP) in insulin-sensitive tissues, especially liver, as determined by LC-ESI-MS/MS. In obese fat-1 mice, t-TUCB raised hepatic 17,18-EEQ and 19,20-EDP levels and reinforced the omega-3-dependent reduction observed in tissue inflammation and lipid peroxidation. t-TUCB also produced a more intense antisteatotic action in obese fat-1 mice, as revealed by magnetic resonance spectroscopy. Notably, t-TUCB skewed macrophage polarization toward an antiinflammatory M2 phenotype and expanded the interscapular brown adipose tissue volume. Moreover, t-TUCB restored hepatic levels of Atg12-Atg5 and LC3-II conjugates and reduced p62 expression, indicating up-regulation of hepatic autophagy. t-TUCB consistently reduced endoplasmic reticulum stress demonstrated by the attenuation of IRE-1α and eIF2α phosphorylation. These actions were recapitulated in vitro in palmitate-primed hepatocytes and adipocytes incubated with 19,20-EDP or 17,18-EEQ. Relatively similar but less pronounced actions were observed with the omega-6 epoxide, 14,15-EET, and nonoxidized DHA. Together, these findings identify omega-3 epoxides as important regulators of inflammation and autophagy in insulin-sensitive tissues and postulate sEH as a druggable target in metabolic diseases.
    Proceedings of the National Academy of Sciences 12/2014; 112(2). DOI:10.1073/pnas.1422590112 · 9.81 Impact Factor
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    ABSTRACT: Hyponatremia is a marker of poor prognosis in patients with cirrhosis. This analysis aimed to assess if hyponatremia also has prognostic value in patients with acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,341 consecutive patients admitted to 29 European centers with acute decompensation of cirrhosis (including ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infections, or any combination of these), both with and without associated ACLF (301 and 1,040 respectively). Of the 301 patients with ACLF, 24.3% had hyponatremia at inclusion compared to 12.3% of 1,040 patients without ACLF (P <0.001). Model for end-stage liver disease, Child-Pugh and chronic liver failure-SOFA scores were significantly higher in patients with ACLF and hyponatremia compared to those without hyponatremia. The presence of hyponatremia (at inclusion or during hospitalization) was a predictive factor of survival both in patients with and without ACLF. The presence of hyponatremia and ACLF was found to have an independent effect on 90-day survival after adjusting for the potential confounders. Hyponatremia in non-ACLF patients nearly doubled the risk (hazard ratio (HR) 1.81 (1.33 to 2.47)) of dying at 90 days. However, when considering patients with both factors (ACLF and hyponatremia) the relative risk of dying at 90 days was significantly higher (HR 6.85 (3.85 to 12.19) than for patients without both factors. Patients with hyponatremia and ACLF had a three-month transplant-free survival of only 35.8% compared to 58.7% in those with ACLF without hyponatremia (P <0.001). The presence of hyponatremia is an independent predictive factor of survival in patients with ACLF. In cirrhosis, outcome of patients with ACLF is dependent on its association with hyponatremia.
    Critical care (London, England) 12/2014; 18(6):700. DOI:10.1186/s13054-014-0700-0
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    ABSTRACT: Cirrhotic patients with acute decompensation frequently develop acute-on chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD) but without ACLF and, to compare this with the Pugh, MELD and MELD-Na scores. The derivation set included 1,016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk was used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use. Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Pugh, MELD and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7 and 8-15 (C-index: 0.72; 0.75 and 0.77 respectively). The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early. Copyright © 2014. Published by Elsevier B.V.
    Journal of Hepatology 11/2014; 62(4). DOI:10.1016/j.jhep.2014.11.012 · 10.40 Impact Factor
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    ABSTRACT: Objective Prognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3). Design The study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver–Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrolment and 48 h after enrolment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network criteria. Results 240 patients (47.1%) met the criteria of ACLF at enrolment, while 98 patients (19.2%) developed AKI. The presence of ACLF and AKI was strongly associated with mortality. 28-day transplant-free mortality and 90-day transplant-free mortality of patients with ACLF (32% and 49.8%, respectively) were significantly higher with respect to those of patients without ACLF (6.2% and 16.4%, respectively; both p<0.001). Corresponding values in patients with and without AKI were 46% and 59%, and 12% and 25.6%, respectively (p<0.0001 for both). ACLF classification was more accurate than AKI classification in predicting 90-day mortality (area under the receiving operating characteristic curve=0.72 vs 0.62; p<0.0001) in the whole series of patients. Moreover, assessment of ACLF classification at 48 h had significantly better prognostic accuracy compared with that of both AKI classification and ACLF classification at enrolment. Conclusions ACLF stratification is more accurate than AKI stratification in the prediction of short-term mortality in patients with acute decompensation of cirrhosis.
    Gut 10/2014; DOI:10.1136/gutjnl-2014-307526 · 13.32 Impact Factor
  • Richard Moreau · Rajiv Jalan · Vicente Arroyo
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    ABSTRACT: A proportion of patients hospitalized for an acute complication of cirrhosis are at high risk of short-term death. The term Acute-on-Chronic Liver Failure (ACLF) is used to characterize these patients. Until recently there was no evidence-based definition of ACLF. In 2013 a definition has been proposed based on results of a large prospective observational European study, called “European Association for the Study of the Liver (EASL)–Chronic Liver Failure (CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC)” study. Results of this study led to elaborate new concepts about ACLF. First, it was found that ACLF is a syndrome that is distinct from mere decompensated cirrhosis. It was also shown that ACLF is a dynamic syndrome which can improve or conversely worsen. Patients who worsen die rapidly from multiorgan failures. The CANONIC study also found that identifiable precipitating events (e.g., bacterial infection, active alcoholism) are found in only 50% of cases of ACLF indicating that these events are dispensable for defining ACLF. In addition precipitating events may be initiators of ACLF but do not drive the outcome. An important concept derived from the CANONIC study is that ACLF is associated with systemic inflammation even in patients who do not have identifiable precipitating events. Finally it was found that ACLF may develop in patients without prior episodes of decompensation or in those with recent decompensation (<3 months). Moreover these patients with “early” ACLF were more severe than patients who developed ACLF after a long of history of decompensated cirrhosis.
    Journal of Clinical and Experimental Hepatology 10/2014; 5(1). DOI:10.1016/j.jceh.2014.09.003
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    Journal of Hepatology 08/2014; 61(2):456. DOI:10.1016/j.jhep.2014.04.008 · 10.40 Impact Factor
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    ABSTRACT: Background & Aims Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections. Methods One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto,DK). Results Patients with AKI (n = 65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs 79 ± 126 μg/gr creatinine,p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n = 40), compared to those with transient AKI (n = 25) (281 ± 477 vs 85 ± 79 μg/gr creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs 429 ± 572 μg/gr creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI. Conclusions In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality.
    Journal of Hepatology 07/2014; 61(1). DOI:10.1016/j.jhep.2014.02.023 · 10.40 Impact Factor

Publication Stats

25k Citations
4,723.56 Total Impact Points

Institutions

  • 2009–2015
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 2000–2015
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
  • 1988–2015
    • Hospital Clínic de Barcelona
      • Servicio de Hepatología
      Barcino, Catalonia, Spain
  • 1975–2015
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2009–2013
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2008–2013
    • Centro de Investigación Biomédica Esther Koplowitz
      Barcino, Catalonia, Spain
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
    • The Andalusian School of Public Health
      Granata, Andalusia, Spain
  • 2011
    • Mansoura University
      • Faculty of Medicine
      El-Manṣûra, Muḩāfaz̧at ad Daqahlīyah, Egypt
  • 2002–2011
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2010
    • The University of Western Ontario
      London, Ontario, Canada
    • Aarhus University Hospital
      • Department of Hepatology and Gastroenterology
      Aarhus, Central Jutland, Denmark
  • 2004–2009
    • Beth Israel Deaconess Medical Center
      • Division of Gastroenterology
      Boston, MA, United States
    • IMD
      Lausanne, Vaud, Switzerland
  • 2007
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 2006–2007
    • Columbia University
      New York, New York, United States
    • Hospital Universitario de Canarias
      San Cristóbal de La Laguna, Canary Islands, Spain
  • 2004–2007
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1988–2007
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
  • 2003–2004
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
    • Yale University
      New Haven, Connecticut, United States
  • 1992–1997
    • University of Florence
      Florens, Tuscany, Italy
  • 1994
    • Autonomous University of Barcelona
      • Department of Medicine
      Cerdanyola del Vallès, Catalonia, Spain
  • 1985–1994
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 1989
    • Queen's University
      • Department of Physiology
      Kingston, Ontario, Canada