Enteropatía hipertensiva en pacientes cirróticos candidatos a trasplante hepático: evaluación endoscópica y relación con el síndrome de hipertensión portal

Los pacientes con cirrosis e hipertensión portal pueden desarrollar varices esofágicas, gastropatía hipertensiva y colopatía hipertensiva, manifestaciones que constituyen un problema de gran importancia en estos pacientes, ya que contribuyen de manera clara a su morbilidad y mortalidad. En los últimos años, el desarrollo de nuevas herramientas endoscópicas como la cápsula endoscópica (CE) y la enteroscopia de doble balón ha permitido mejorar la calidad del estudio del intestino delgado y demostrar la existencia de lesiones intestinales en los pacientes con cirrosis e hipertensión portal, que se han denominado “enteropatía hipertensiva” (EHT). La primera descripción de estas lesiones la realizó De Palma en 2005, comunicando la existencia tanto de lesiones de tipo inflamatorio como de lesiones vasculares: angiodisplasias, varices, etc. No obstante, la prevalencia, criterios diagnósticos e importancia clínica de esta condición no son bien conocidos. Por un lado, no existe información detallada sobre la precisión de la CE en el diagnóstico de EHT en los pacientes cirróticos. El único estudio publicado hasta la fecha que evalúa el acuerdo interobservador en la interpretación de los hallazgos de EHT tras el estudio con CE comunica una concordancia del 100%. Sin embargo, este resultado no ha sido validado posteriormente. Tampoco se conoce la prevalencia de esta condición en los pacientes candidatos a trasplante hepático, población extremadamente sensible por su gravedad y por las posibles implicaciones de la EHT durante la permanencia del paciente en la lista de espera. Por otra parte, se desconoce la importancia clínica de esta manifestación endoscópica de los pacientes con hipertensión portal. Mientras algunos estudios no han demostrado una asociación entre la presencia de lesiones intestinales y el valor de la hemoglobina, otros han encontrado sangrado activo en el momento del estudio endoscópico y otros una contribución a la anemia de los pacientes cirróticos debido a las pérdidas crónicas ocultas..

Development and Validation of Hepamet Fibrosis Scoring System A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis

Background & Aims Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. Methods We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. Results Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05). Conclusions Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis

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

[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 F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 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.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

The role of statins on helicobacter pylori eradication : Results from the european registry on the management of h. pylori (hp-eureg)

Funding: This project was promoted and funded by the European Helicobacter and Microbiota Study Group (EHMSG), the Spanish Association of Gastroenterology (AEG), and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).Peer reviewedPublisher PD

Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD)

Background: recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, dia betes me llitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and acti vator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. Aim and methods: six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuri cemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divid ed into three groups according to the tertile levels of serum uric acid and gender. Results: the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pres sure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08 3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87). Conclusion: higher levels of serum uric acid were inde pendently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage

Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD)

[Background] recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis.[Aim and methods] six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender.[Results] the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87).[Conclusion] higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage.Peer reviewe

Development and Validation of Hepamet Fibrosis Scoring System–A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis

HEPAmet Registry.[Background & Aims] Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis.[Methods] We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios.[Results] Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05).[Conclusions] Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis

Noninvasive prediction of outcomes in autoimmune hepatitis-related cirrhosis

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy

Outcomes and factors associated with relapse of vaccine-induced liver injury after SARS CoV-2 immunization: A nationwide study

Introduction and Objectives: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. Patients and Methods: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. Results: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). Conclusions: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury