Salvador Augustín

Vall d'Hebron Institut de Recerca

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Joan Genescà

Universitat Autònoma de Barcelona

Juan G. Abraldeṣ

University of Alberta

Agustı́n Albillos

Hospital Universitario Ramón y Cajal

José Luís Calleja

Hospital Universitario Puerta de Hierro Majadahonda

Rafael Bañares

Hospital General Universitario Gregorio Marañón

Juan Carlos García‐Pagán

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Manuel Romero‐Gómez

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

Javier Crespo

Instituto de Investigación Marqués de Valdecilla

Marı́a Martell

University of Minnesota

Rafael Esteban

Vall d'Hebron Institut de Recerca

Cooperative Institutions

McMaster University

513

University of Pennsylvania

329

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

321

Instituto de Salud Carlos III

283

Universitat Autònoma de Barcelona

275

Inserm

259

Vall d'Hebron Hospital Universitari

216

Universitat de Barcelona

201

Vall d'Hebron Institut de Recerca

190

University College London

187

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Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: The “Anticipate” study

Hepatology (2016)

Juan G. Abraldeṣ Christophe Bureau Horia Ștefănescu Salvador Augustín Michael Ney

In patients with compensated advanced chronic liver disease (cACLD), the presence of clinically significant portal hypertension (CSPH) and varices needing treatment (VNT) bears prognostic and therapeutic implications. Our aim was to develop noninvasive tests-based risk prediction models to provide a point-of-care risk assessment of cACLD patients. We analyzed 518 patients with cACLD from five centers in Europe/Canada with paired noninvasive tests (liver stiffness measurement [LSM] by transient elastography, platelet count, and spleen diameter with calculation of liver stiffness to spleen/platelet score [LSPS] score and platelet-spleen ratio [PSR]) and endoscopy/hepatic venous pressure gradient measurement. Risk of CSPH, varices, and VNT was modeled with logistic regression. All noninvasive tests reliably identified patients with high risk of CSPH, and LSPS had the highest discrimination. LSPS values above 2.65 were associated with risks of CSPH above 80%. None of the tests identified patients with very low risk of all-size varices, but both LSPS and a model combining TE and platelet count identified patients with very low risk (<5%) risk of VNT, suggesting that they could be used to triage patients requiring screening endoscopy. LSPS values of <1.33 were associated with a <5% risk of VNT, and 26% of patients had values below this threshold. LSM combined with platelet count predicted a risk <5% of VNT in 30% of the patients. Nomograms were developed to facilitate point-of-care risk assessment.A significant proportion of patients with a very high risk of CSPH, and a population with a very low risk of VNT can be identified with simple, noninvasive tests, suggesting that these can be used to individualize medical care. (Hepatology 2016;64:2173-2184).

Transient elastography

Nomogram

10.1002/hep.28824

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Citations (303)

Hemodynamic response–guided therapy for prevention of variceal rebleeding: An uncontrolled pilot study

Hepatology (2006)

Antonio González Salvador Augustín Mercedes Pérez Joan Dot Esteban Saperas

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (≥20% decrease in HVPG from baseline) were maintained on drugs, partial responders (≥10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal-systemic shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis. (HEPATOLOGY 2006;44:806–812.)

Haemodynamic response

10.1002/hep.21343

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Citations (59)

Synergic effect of a combined treatment with atorvastatin and ambrisentan in a rat model of NASH

Journal of Hepatology (2020)

Miren Bravo Imma Raurell Salvador Augustín Joan Genescà Marı́a Martell

Ambrisentan

10.1016/s0168-8278(20)31812-2

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Citations (0)

Bacterial deoxyribonucleic is frequent in blood samples of patients with compensated cirrhosis and obesity and is associated with lack of decrease of portal pressure after an intensive lifestyle intervention

Journal of Hepatology (2017)

Rubén Francés A. Albillos Càndid Villanueva Joan Genescà Alba Ardèvol

10.1016/s0168-8278(17)30529-9

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Citations (0)

Effect of Current Therapies Aimed at Preventing Variceal Rebleeding on Other Complications of Cirrhosis

Springer eBooks (2015)

Cristina Ripoll Salvador Augustín Thomas Reiberger Richard Moreau Francesco Salerno

10.1007/978-3-319-23018-4_33

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Citations (1)

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy‐proven nonalcoholic fatty liver disease subjects

Liver International (2021)

Javier Ampuero R. Aller Rocío Gallego‐Durán Javier Crespo Javier Abad

Abstract Background and Aim Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic‐associated fatty liver disease (MAFLD). Methods Spanish multicenter study including 1893 biopsy‐proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow‐up (4.7 ± 3.8 years). Results Fibrosis was F 0 34.3% (649/1893), F 1 27% (511/1893), F 2 16.5% (312/1893), F 3 15% (284/1893) and F 4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F 0 (33.6%) to F 2 (68.6%), and decreased significantly in F 4 patients (51.8%) ( P = .0001). More than 70% of non‐NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) ( P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these. Conclusions The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.

Steatosis

Nonalcoholic steatohepatitis

Steatohepatitis

10.1111/liv.14898

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Citations (15)

The restoration of a healthy intestinal microbiota by fecal transplantation normalizes portal hypertension and endothelial dysfunction in a rat model of diet-induced non-alcoholic steatohepatitis

Journal of Hepatology (2017)

Teresa García‐Lezana Marı́a Martell Imma Raurell Miren Bravo Manuel Torres‐Arauz

Steatohepatitis

Fecal bacteriotherapy

10.1016/s0168-8278(17)30390-2

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Citations (3)

Natural history and prognostic factors of compensated cirrhosis secondary to non-alcoholic steatohepatitis in Catalonia

Journal of Hepatology (2020)

Octavi Bassegoda Jesús Rivera Serra Matamala Isabel Rosa Ma Morillas Teresa Broquetas

Steatohepatitis

10.1016/s0168-8278(20)30795-9

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Citations (0)

Synergic effect of atorvastatin and ambrisentan on sinusoidal and hemodynamic alterations in a rat model of NASH

Disease Models & Mechanisms (2021)

Miren Bravo Imma Raurell Aurora Barberá Diana Hide Mar Gil

In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or a combination of both for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblotting. Conditioned media experiments were performed with LSEC. HSCs were characterized by RT-PCR, and a collagen lattice contraction assay was performed. Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamics and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype, thus improving endothelial function, whereas ambrisentan prevented the contractile response in HSCs by blocking ET-1 response. Additionally, ambrisentan also increased eNOS (also known as Nos3) phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the serum alanine aminotransferase of the combined treatment group decreased to normal levels, and this group exhibited a restoration of the HSC quiescent phenotype. The combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for NASH patients.

Ambrisentan

Steatohepatitis

10.1242/dmm.048884

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Citations (20)

Metabolomics as a tool to predict the risk of decompensation or liver-related death in patients with compensated cirrhosis

Hepatology (2023)

Oana Nicoară-Farcău Juan José Lozano Cristina Alonso Julia Sidorova Càndid Villanueva

Background and Aims: Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG > 10 mm Hg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcomes in these compensated patients. Approach and Results: This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. placebo in 201 patients with compensated cirrhosis and CSPH), including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p -value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model, including HVPG, Child-Pugh, and treatment received ( HVPG/Clinical model ), had a C-index of 0.748 (CI95% 0.664–0.827). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model’s performance [C-index of 0.808 (CI95% 0.735–0.882); p =0.032]. The combination of these 2 metabolites together with Child-Pugh and the type of treatment received (Clinical/Metabolite model) had a C-index of 0.785 (CI95% 0.710–0.860), not significantly different from the HVPG-based models including or not metabolites. Conclusions: In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG.

Decompensation

Clinical endpoint

Univariate analysis

10.1097/hep.0000000000000316

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Citations (9)