Liver disease is frequently asymptomatic, challenging early identification in the primary care setting. The fibrosis 4 (FIB4) index is a liver fibrosis biomarker that is a potential alternative to ...liver biopsy for diagnosing and managing liver disease. This study aimed to calculate the FIB4 index for screening individuals at high risk of liver disease at the community level. This was a retrospective real-world study analyzing blood and serum test results from a central laboratory. The primary outcome was the number of individuals within each risk category for hepatic fibrosis: high risk (FIB4 ≥ 3.25) and low risk (FIB4 < 1.3). The analysis included samples from 31,753 patients, of which 18,102 were aged 40 to 75 years. In these patients, the FIB4 index had been explicitly requested in 1852 (10.2%) cases and estimated ad hoc in the rest. Of the 263 (1.5%) cases with FIB4 ≥ 3.25, the FIB4 index was requested in 46 (17.5%), and 52 (19.8%) showed evidence of liver fibrosis in their medical records, while the rest did not report any data regarding liver fibrosis. FIB4 is a simple score that can play a role as a "red flag" for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care.
Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and ...exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient HVPG ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16‐week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health‐related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, –5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (–23.7 ± 19.9% vs. –8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End‐Stage Liver Disease scores did not change. Conclusion: Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293‐1305).
ObjectivesTo evaluate the potential association between chronic exposure to medication and death related to COVID-19.MethodsThis is a retrospective cross-sectional study that included all patients ...hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality.ResultsThe study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death.ConclusionsThis study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance.
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. Conclusion: 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).
Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD ...remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension AHT, and dyslipidemia) in metabolically healthy patients.
We included 178 metabolically healthy—defined by the absence of baseline T2DM, AHT, dyslipidemia—patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia.
During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19–7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14–5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% 4/16 vs. HFS <0.12 4.5% 4/88; logRank 6.658, p = 0.010).
Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM.
Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
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•NAFLD-related significant fibrosis predicts the occurrence of type 2 diabetes mellitus and arterial hypertension.•The annual incidence of metabolic outcomes is four-times higher in the presence of significant fibrosis.•Neither steatosis nor NASH predict the appearance of metabolic outcomes.•Hepamet fibrosis score >0.12 is associated with the risk of developing type 2 diabetes mellitus.
Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal ...microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages. In stage 1, Sprague‐Dawley rats were fed for 8 weeks a high‐fat, high‐glucose/fructose diet (HFGFD) or a control diet/water (CD). Representative rats were selected as IM donors for stage 2. In stage 2, additional HFGFD and CD rats underwent intestinal decontamination, followed by IM transplantation with feces from opposite‐diet donors (heterologous transplant) or autologous fecal transplant (as controls), generating four groups: CD‐autotransplanted, CD‐transplanted, HFGFD‐autotransplanted, HFGFD‐transplanted. After IM transplantation, the original diet was maintained for 12‐14 days until death. HFGFD rats developed obesity, insulin resistance, NASH without fibrosis but with PH, intrahepatic endothelial dysfunction, and IM dysbiosis. In HFGFD rats, transplantation with feces from CD donors caused a significant reduction of PH to levels comparable to CD without significant changes in NASH histology. The reduction in PH was due to a 31% decrease of intrahepatic vascular resistance compared to the HFGFD‐autotransplanted group (P < 0.05). This effect occurs through restoration of the sensitivity to insulin of the hepatic protein kinase B–dependent endothelial nitric oxide synthase signaling pathway. Conclusion: The IM exerts a direct influence in the development of PH in rats with diet‐induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (Hepatology 2018;67:1485‐1498)
Early placement of a transjugular intrahepatic portosystemic shunts (TIPS) is considered the treatment of choice for patients with acute variceal bleeding (AVB) and cirrhosis who have a high risk of ...death (Child-Pugh class B with active bleeding at endoscopy or Child-Pugh class C). It has been proposed that patients of Child-Pugh class B, even with active bleeding, should not be considered high risk. Alternative criteria have been proposed for identification of high-risk patients, such as Child-Pugh class C with plasma level of creatinine of 1 mg/dL or more (ChildC-C1) and a model for end-stage liver disease (MELD) score of 19 or more. We analyzed outcomes of a large cohort of patients with AVB who received the standard of care at different centers to validate these systems of risk stratification.
We performed an observational study of 915 patients with liver cirrhosis and AVB who received standard treatment (drugs, antibiotics, and endoscopic ligation, with TIPS as the rescue treatment), over different time periods between 2006 and 2014 in Canada and Europe. All patients were followed until day 42 (week 6) after index AVB or death. Child-Pugh and MELD scores were calculated at time of hospital admission. The primary outcome was mortality 6 weeks after index AVB among patients who met the early TIPS criteria (Child-Pugh class B with active bleeding at endoscopy or Child-Pugh class C), MELD19 criteria (patients with MELD scores of 19 or more), and ChildC-C1 criteria.
Among 915 patients with AVB, 18% died within 6 weeks. Among the 523 patients who met the early TIPS criteria, 17% died within 6 weeks. All 3 rules discriminated patients at high risk of death from those with low risk: 28.3% of the patients classified as high risk by the early TIPS criteria died whereas only 7.0% of patients classified as low risk died; 46.0% of patients classified as high risk by the MELD19 criteria died vs 8.1% of patients classified as low risk; 51.9% of patients classified as high risk by the ChildC-C1 criteria died compared with 10.9% of patients classified as low risk. Mortality was significantly lower among patients with Child-Pugh class B (11.7%) than with Child-Pugh class C (35.6%) (P ≤ .001). Mortality was similar between patients with Child-Pugh class B cirrhosis with or without active bleeding (11.7%). Patients with Child-Pugh class A cirrhosis or MELD scores of 11 or less had low mortality (2%-4%), patients with Child-Pugh class B cirrhosis or MELD scores of 12 to 18 had intermediate mortality (10%-12%), and patients with Child-Pugh class C cirrhosis or MELD scores of 19 or more had high mortality (22%-46%).
Patients with Child-Pugh class B cirrhosis and AVB who receive standard therapy, regardless of the presence of active bleeding, have 3-fold lower mortality than patients with Child-Pugh C cirrhosis and might not need TIPS. Patients with Child-Pugh class C and/or MELD scores of 19 or more should be considered at high risk of death. These findings might help refine criteria for early TIPS.
Investigar la prevalencia de la morbilidad metabólica (MM) en población penitenciaria.
Estudio observacional, transversal y multicéntrico.
Los 9 centros penitenciarios de Cataluña.
Reclusos que no ...están en «régimen abierto» y, por consiguiente, dependen sanitariamente de los equipos de atención primaria penitenciaria (EAPP).
Se consideraron internos con MM los que presentaban al menos un componente del síndrome metabólico: obesidad, hipertensión arterial, diabetes tipo2 y/o dislipidemia. Se estudiaron variables antropométricas, antecedentes clínicos y parámetros analíticos asociados a la MM. Fuente de información: Sistema de Información de los Servicios de Atención Primaria de Cataluña (SISAP).
Cálculo de prevalencia de la MM, total y por categorías. Para estudiar variables asociadas se realizó un análisis de regresión logística multivariante, calculándose la odds ratio ajustada (ORA) con intervalo de confianza del 95%.
Un total de 4.338 internos estudiados: el 93,9% hombres, edad media 38,4años, 51,7% de la Unión Europea y 6,7% (8,2% de los analizados) infectados por VIH. Presentaron más MM los de más edad y las personas infectadas por VIH y menos los europeos de países no miembros de la Unión Europea, los del Magreb y los del África subsahariana.
La prevalencia de MM es alta en presos, aun siendo una población joven, especialmente en reclusos de mayor edad y en infectados por VIH. La prevalencia varía mucho según el origen geográfico. Es conveniente que la MM sea detectada precozmente para evitar complicaciones. La prevención, la detección y el manejo terapéutico deben ser actividades prioritarias de la atención primaria penitenciaria.
To investigate the prevalence of metabolic morbidity (MM) amongst prison inmates.
Multicentric, cross-sectional observational study.
All (nine) prisons in Catalonia.
Convicted inmates that are not in an «open regime», whose healthcare relies on the Prison Primary Care Teams.
MM was defined as the presence of at least one component of the metabolic syndrome, i.e., obesity, arterial hypertension, type2 diabetes, and/or dyslipidemia. The variables collected included anthropometric measurements, medical history and laboratory values related to MM. The source of information was the Catalan Primary Healthcare Services Information System (SISAP).
The prevalence of MM, overall and by several participant subcategories, was calculated. To investigate the risk factors associated to a higher prevalence of MM, a multivariable logistic regression analysis was carried out and expressed as adjusted odds ratios and 95% confidence intervals.
4338 inmates were studied, of whom 93.9% were male. Mean age was 38.4years, 51.7% were born in European Union countries, and 6.7% were infected by HIV. The variables associated with a significantly increased risk of presenting MM were older age and HIV infection, whereas certain geographical origins (i.e., non-UE European countries, Maghreb and Sub-Saharan Africa) were associated with lower risk of MM.
In spite of being an overall young population, prison inmates present high rates of MM. Older age, HIV infection and geographic origin appear as the most strongly associated factors with MM in the prison population. MM should be detected early in order to prevent complications. Prevention, screening and treatment of MM ought to be considered a priority in the clinical routine of prison healthcare professionals.
Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and ...severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.
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