Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study / Factores de riesgo para la progresión de la fibrosis en la esteatohepatitis no alcohólica: análisis de la cohorte europea en el estudio GAIN del mundo real

Objective To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH.Patients and methodsPhysician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model.ResultsOverall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12–1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68–11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19–2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30–7.63; p=0.010) times higher for those unable to work due to NASH.ConclusionsDisease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH. (AU)

Objetivo Para comprender mejor los factores que impulsan la progresión de la enfermedad en la esteatohepatitis no alcohólica (NASH), evaluamos los marcadores clínicos y sociodemográficos de la progresión de la fibrosis en adultos con NASH.Pacientes y métodosSe utilizaron las características demográficas y clínicas de los pacientes informadas por los médicos del estudio de Evaluación Global del Impacto de NASH (GAIN) del mundo real. Los factores asociados con la probabilidad de progresión de la fibrosis desde el diagnóstico de EHNA se identificaron mediante un modelo de regresión logística.ResultadosEn total, se incluyeron 2.349 pacientes en Europa del estudio GAIN; la edad media fue 54,6 años y el 41% eran mujeres. Las covariables significativas incluyeron edad, años desde el diagnóstico, situación laboral, estadio de fibrosis en el momento del diagnóstico, diabetes mellitus tipo 2, hipertensión, trasplante de hígado y biopsia de hígado en el momento del diagnóstico. El riesgo de progresión fue 1,16 (intervalo de confianza del 95% 1,12-1,20; p < 0,001) veces mayor por cada año adicional desde el diagnóstico de EHNA y 5,43 (2,68-11,37; p < 0,001) veces mayor cuando los médicos propusieron un trasplante de hígado. en el momento del diagnóstico. En comparación con los pacientes empleados a tiempo completo, el riesgo de progresión fue 1,77 (1,19-2,60; p = 0,004) veces mayor para los pacientes desempleados y 3,16 (1,30-7,63; p = 0,010) veces mayor para aquellos que no podían trabajar debido a a NASH.ConclusionesLa duración de la enfermedad, la gravedad de NASH y la presencia de otras comorbilidades metabólicas podrían ayudar a evaluar el riesgo de progresión en pacientes con NASH. (AU)

Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action.

Nonalcoholic fatty liver disease or metabolic-associated fatty liver disease (MAFLD) is a common condicion with increasing prevalence and incidence, specially in patients with type 2 diabetes mellitus (T2DM). Both cardiovascular and renal disease are clearly increased in these patients, particularly in those with diabetic nephropathy. In the liver-heart-kidney-metabolic axis, the common pathophysiological basis of MAFLD, cardiovascular disease (CVD), chronic kidney disease (CKD), and T2DM is the same. The clinical relationship between all of them is clear and is multidirectional: MAFLD may precede the development of cardiovascular and renal disease, and may also worsen the prognosis of these complications once developed. In this review we emphasize the importance of targeting MAFLD in Diabetic kidney disease, with the goal of detecting high-risk patients in order to improve their prognosis.

Esteatosis hepática metabólica y nefropatía diabética: una llamada a la acción / Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action

La incidencia y la prevalencia de hígado graso no alcohólico o enfermedad hepática metabólica (EHmet) está en aumento y es mayor en pacientes con diabetes mellitus tipo 2 (DM2). El riesgo cardiovascular y renal está claramente incrementado en estos pacientes, especialmente cuando se desarrolla nefropatía diabética. El eje cardio-reno-hepato-metabólico, conformado por la enfermedad cardiovascular (ECV), la enfermedad renal crónica (ERC), la EHmet y la DM2, tiene una base fisiopatogénica común. La relación clínica entre todos los componentes es inevitable y multidireccional, pudiendo la EHmet preceder al desarrollo de complicaciones cardiovasculares y renales, y también empeorar el pronóstico de las mismas una vez desarrolladas. En esta revisión enfatizamos la importancia de buscar y tratar la EHmet en pacientes con ERC y DM2 con el objetivo de identificar pacientes de mayor riesgo y de mejorar su pronóstico.(AU)

Non-alcoholic fatty liver disease or metabolic-associated fatty liver disease (MAFLD) is a common condition with increasing prevalence and incidence, specially in patients with type 2 diabetes mellitus (DM2). Both cardiovascular and renal disease are clearly increased in these patients, particularly in those with diabetic nephropathy. In the liver–heart–kidney–metabolic axis, the common pathophysiological basis of MAFLD, cardiovascular disease (CVD), chronic kidney disease (CKD), and DM2 is the same. The clinical relationship between all of them is clear and is multidirectional: MAFLD may precede the development of cardiovascular and renal disease, and may also worsen the prognosis of these complications once developed. In this review we emphasize the importance of targeting MAFLD in diabetic kidney disease, with the goal of detecting high-risk patients in order to improve their prognosis.(AU)

Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi / Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study

Objetivo: Describir de manera detallada la epidemiología, diagnóstico, manejo clínico, opciones de tratamiento, impacto en la calidad de vida y necesidades no cubiertas de los pacientes con fibrosis hepática avanzada (F3-F4) asociada a esteatohepatitis no alcohólica (NASH) en España. Metodología: Estudio Delphi de dos rondas de consulta con 41 hepatólogos expertos de 16 comunidades autónomas para recoger su experiencia en práctica clínica. Resultados: La prevalencia estimada de pacientes adultos diagnosticados de fibrosis F3-F4 asociada a NASH en España es de 0,019% (intervalo de confianza [IC] 95%: 0,019-0,020%). Aproximadamente 7.588 adultos con este padecimiento están actualmente diagnosticados y son manejados en los Servicios de Aparato Digestivo de los hospitales españoles, y alrededor de 1.881 nuevos pacientes son diagnosticados cada año. El manejo es multidisciplinar e incluye las especialidades de Aparato Digestivo, Endocrinología y Medicina interna, considerando las frecuentes comorbilidades metabólicas asociadas (obesidad, diabetes mellitus tipo 2 o sobrecarga férrica dismetabólica). A pesar del claro impacto en la calidad de vida, este no se evalúa rutinariamente en la práctica clínica. Las técnicas diagnósticas no invasivas más utilizadas son la elastografía de transición y el índice de fibrosis hepática 4 (FIB-4). La ausencia de tratamientos eficaces y seguros se presenta como la principal necesidad no cubierta para el manejo de estos pacientes. Conclusiones: Este estudio proporciona una representación de la situación actual de los pacientes diagnosticados con fibrosis F3-F4 asociada a NASH en España, incrementando la evidencia disponible y contribuyendo a la toma de decisiones informadas por parte de los profesionales y el sistema sanitario. (AU)

Objective: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. Methodology: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. Results: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. Conclusions: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system. (AU)

Vinpocetine represses the progression of nonalcoholic steatohepatitis in mice by mediating inflammasome components via NF-KB signaling / La vinpocetina reprime la progresión de la esteatohepatitis no alcohólica en ratones por mediación de los componentes del inflamasoma a través de la señalización NF-KB

Background: Inflammasome activation is known to be involved in nonalcoholic steatohepatitis (NASH). Vinpocetine is a derivative of vincamine and is reported to suppress the activation of inflammasome. Methods: This study explored the therapeutical potential of Vinpocetine on NASH. Mice were fed with a choline-deficient (MCD) or chow diet in the presence or absence of Vinpocetine for 8 weeks. H&E staining and biochemical assays were determined to evaluate the hepatic steatosis and fibrosis symptoms. In addition, primary hepatocytes and Kupffer cells were isolated and induced by MCD or lipopolysaccharides/cholesterol crystals with or without Vinpocetine. ELISAs, qPCR, and Western blotting were applied to determine the levels of NASH-related biomarkers in both in vivo mouse model and in vitro cell models. Results: Treatment of Vinpocetine did not cause observable side effects against and MCD-induced cells and mouse NASH model. However, treatment of Vinpocetine ameliorated hepatic steatosis and fibrosis and suppressed the levels of alanine transaminase and aspartate transferase in the mouse NASH model. In addition, treatment of Vinpocetine suppressed the mRNA and protein levels of inflammasome components both in vitro and in vivo. Conclusion: Vinpocetine suppressed NASH in mice by mediating inflammasome components via nuclear factor κB signaling. (AU)

Antecedentes: Se sabe que la activación del inflamasoma está implicada en la esteatohepatitis no alcohólica (EHNA). La vinpocetina es un derivado de la vincamina que, según los informes, suprime la activación del inflamasoma. Métodos: Este estudio exploró el potencial terapéutico de la vinpocetina en la EHNA. Durante 8 semanas se alimentó a ratones con una dieta deficiente en colina (MCD) o con una dieta chow en presencia o ausencia de vinpocetina. Se realizaron tinciones de H&E y ensayos bioquímicos para evaluar los síntomas de esteatosis hepática y fibrosis. Además, se aislaron hepatocitos primarios y células de Kupffer y se indujeron mediante MCD o cristales de lipopolisacáridos/colesterol con o sin vinpocetina. Se aplicaron ELISA, qPCR y Western blotting para determinar los niveles de biomarcadores relacionados con la EHNA tanto en el modelo de ratón in vivo como en los modelos celulares in vitro. Resultados: El tratamiento con vinpocetina no causó efectos secundarios observables contra las células y el modelo de ratón de EHNA inducidos por MCD. Sin embargo, el tratamiento con vinpocetina mejoró la esteatosis hepática y la fibrosis y suprimió los niveles de alanina transaminasa y de aspartato transferasa en el modelo de EHNA de ratón. Además, el tratamiento con vinpocetina suprimió los niveles de ARNm y proteínas de los componentes del inflamasoma tanto in vitro como in vivo. Conclusiones: La vinpocetina suprimió la EHNA en ratones por mediación de los componentes del inflamasoma a través de la señalización del factor nuclear κB. (AU)

Metabolic disorders across the body mass index spectrum in a Colombian population with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: The relationship between obesity and nonalcoholic fatty liver disease (NAFLD) has long been established, and the prevalence of both conditions has grown together. Recent interest in NAFLD in nonobese individuals has led to an increasing number of studies, especially in Asia. Despite the fact that the prevalence of NAFLD in Latin America is one of the highest in the world, there is a lack of information on lean NAFLD populations from the region. The aim of the present study was to assess the risk of metabolic comorbidities across the whole body mass index spectrum when nonalcoholic steatohepatitis (NASH) was first diagnosed in a Latin American population. METHODS: A single-center, cross-sectional study on Colombian patients newly diagnosed with NAFLD, within the time frame of 2010-2020, compared their metabolic biochemical profile, liver enzymes, risk of prevalent metabolic abnormalities, and liver disease. RESULTS: Data from 300 patients were collected. Ninety-two percent of the patients were men and the median patient age was 47 (IQR 20) years. We found no significant differences in the biochemical, metabolic profile, or liver enzyme plasma concentration between lean, overweight, and obese individuals. Obese patients had significantly higher LDL cholesterol, and a higher risk of dyslipidemia (OR 1.86, 95% CI 1.14-3.05). Every 1kg increase in body weight increased the risk of having NASH by 2% (95% CI 2-4). CONCLUSIONS: We evaluated the metabolic risk across the entire body mass index spectrum in a Colombian cohort with NAFLD and presented the characteristics of what we believe is the first Latin American lean NAFLD population to be described.

Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study. / Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi.

OBJECTIVE: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. METHODOLOGY: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. RESULTS: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. CONCLUSIONS: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system.

Vinpocetine represses the progression of nonalcoholic steatohepatitis in mice by mediating inflammasome components via NF-κB signaling.

BACKGROUND: Inflammasome activation is known to be involved in nonalcoholic steatohepatitis (NASH). Vinpocetine is a derivative of vincamine and is reported to suppress the activation of inflammasome. METHODS: This study explored the therapeutical potential of Vinpocetine on NASH. Mice were fed with a choline-deficient (MCD) or chow diet in the presence or absence of Vinpocetine for 8 weeks. H&E staining and biochemical assays were determined to evaluate the hepatic steatosis and fibrosis symptoms. In addition, primary hepatocytes and Kupffer cells were isolated and induced by MCD or lipopolysaccharides/cholesterol crystals with or without Vinpocetine. ELISAs, qPCR, and Western blotting were applied to determine the levels of NASH-related biomarkers in both in vivo mouse model and in vitro cell models. RESULTS: Treatment of Vinpocetine did not cause observable side effects against and MCD-induced cells and mouse NASH model. However, treatment of Vinpocetine ameliorated hepatic steatosis and fibrosis and suppressed the levels of alanine transaminase and aspartate transferase in the mouse NASH model. In addition, treatment of Vinpocetine suppressed the mRNA and protein levels of inflammasome components both in vitro and in vivo. CONCLUSION: Vinpocetine suppressed NASH in mice by mediating inflammasome components via nuclear factor κB signaling.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study.

OBJECTIVE: To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. PATIENTS AND METHODS: Physician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. RESULTS: Overall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12-1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68-11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19-2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30-7.63; p=0.010) times higher for those unable to work due to NASH. CONCLUSIONS: Disease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Prevalencia de esteatosis hepática no alcohólica en una ciudad española: estudio poblacional / Prevalence of nonalcoholic fatty liver disease in a Spanish town: A population-based study

Objetivo La esteatosis hepática no alcohólica (EHNA) es la causa más importante de esteatosis hepática e hipertransaminasemia en los países occidentales. El objetivo consistía en determinar la prevalencia de EHNA entre 261025 personas del área de salud pública de Valladolid Este en España. Métodos Se seleccionó al azar a 1800 participantes a partir de una base de datos de tarjetas del sistema sanitario público, que fueron representativos de la mayor parte de la población. En todos los pacientes se realizó una historia clínica, medición de parámetros antropométricos, ecografía abdominal y análisis de sangre para descartar hepatopatía. También se calculó la puntuación FLI en todos los casos. Resultados Cuatrocientos cuarenta y ocho participantes aceptaron participar en el estudio. La prevalencia de EHNA en nuestro estudio fue del 22,3% (18,5-26,2%). La prevalencia fue máxima entre los 50 y los 70 años, y se incrementó con la edad (p <0,006). No hubo diferencias significativas en cuanto al sexo (p=0,338). La mediana del índice de masa corporal fue de 27,2 y la EHNA se relacionó con el peso (p <0,001) y el perímetro abdominal (p <0,001). El análisis de regresión logística reveló que una γ-GT inferior a 26 UI/ml, un índice de masa corporal superior a 31 y una puntuación HOMA-IR superior a 2,54 fueron factores predictivos independientes de EHNA en la muestra. El diagnóstico de EHNA se correspondió con una puntuación FLI elevada en el 88% de los casos. Conclusiones De acuerdo con otros estudios epidemiológicos, la prevalencia de EHNA es muy alta. Un estudio completo con consulta clínica, estudios de imagen y análisis de sangre en todos los pacientes permite determinar la prevalencia de EHNA en la población (AU)

Objective Nonalcoholic fatty liver disease (NAFLD) is western countries’ most important cause of hepatic steatosis and hypertransaminasemia. The objective was to evaluate the prevalence of NAFLD among 261,025 people in the East Valladolid public healthcare area in Spain. Methods We randomly selected 1800 participants from a public healthcare system card database, representing most of the population. We performed a medical record, measurement of anthropometric parameters, abdominal ultrasound, and blood tests to rule out hepatic disease in all patients. We calculated the FLI score in all patients. Results Four hundred and forty-eight participants agreed to participate in the study. The prevalence of nonalcoholic fatty liver disease in our study was 22.3% [18.5–26.2%]. Prevalence was highest between 50 and 70 years, increasing with age (p < 0.006). There were no significant differences in sex (p = 0.338). The median body mass index was 27.2, and NAFLD was related to the weight (p < 0.001) and abdominal perimeter (p < 0.001). Logistic regression analysis showed GGT lower than 26UI/ml, body mass index higher than 31, and HOMA IR greater than 2.54 as independent factors to predict NAFLD in the sample. NAFLD diagnosis matched with an elevated FLI score in 88% of cases. Conclusion According to other epidemiological studies, NAFLD's prevalence is very high. A complete study with a clinical consultation, image studies, and blood tests in all patients allows us to assess the prevalence of NAFLD in the population (AU)

Prevalence of nonalcoholic fatty liver disease in a Spanish town: a population-based study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is western countries' most important cause of hepatic steatosis and hypertransaminasemia. The objective was to evaluate the prevalence of NAFLD among 261,025 people in the East Valladolid public healthcare area in Spain. METHODS: We randomly selected 1800 participants from a public healthcare system card database, representing most of the population. We performed a medical record, measurement of anthropometric parameters, abdominal ultrasound, and blood tests to rule out hepatic disease in all patients. We calculated the FLI score in all patients. RESULTS: 448 participants agreed to participate in the study. The prevalence of nonalcoholic fatty liver disease in our study was 22.3% [18.5%-26.2%]. Prevalence was highest between 50 and 70 years, increasing with age (p < 0.006). There were no significant differences in sex (p = 0.338). The median Body mass index was 27.2, and NAFLD was related to the weight (p < 0,001) and abdominal perimeter (p < 0.001). Logistic regression analysis showed GGT lower than 26 UI/ml, body mass index higher than 31, and HOMA IR greater than 2.54 as independent factors to predict NAFLD in the sample. NAFLD diagnosis matched with an elevated FLI score in 88% of cases. CONCLUSION: According to other epidemiological studies, NAFLD's prevalence is very high. A complete study with a clinical consultation, image studies, and blood tests in all patients allows us to assess the prevalence of NAFLD in the population.

Bariatric surgery and non-alcoholic fatty liver disease / Cirugía bariátrica e hígado graso no alcohólico

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that may lead to cirrhosis and hepatocellular carcinoma; its close relationship with obesity and the metabolic syndrome involves an increasing prevalence. Invasive liver biopsy is the gold standard diagnosis technique for NAFLD but entails risks. Therefore, transient elastography, a non-invasive technique with high reliability, is frequently used in clinical practice. Bariatric surgery is the only effective treatment for long-term weight loss and obesity-related metabolic conditions improvement. Although studies report encouraging results of bariatric surgery as a valuable therapy for NAFLD, guidelines for its use in NAFLD are ambiguous. Indeed, the mechanisms driving this improvement are largely unknown, but likely involve weight loss-dependent and independent factors including anatomic and hormonal changes. This review aims to update the relationship between NAFLD and bariatric surgery, focusing on the indications for surgery and the mechanisms implied in NAFLD improvement. (AU)

El hígado graso no alcohólico (HGNA) es una enfermedad crónica que puede conducir a cirrosis y hepatocarcinoma; su relación con la obesidad y el síndrome metabólico supone un aumento en su prevalencia. La biopsia hepática es la prueba diagnóstica de elección, pero implica riesgos. En consecuencia, la elastografía hepática, una técnica no invasiva con una alta fiabilidad, es utilizada frecuentemente en la práctica clínica. La cirugía bariátrica es el único tratamiento eficaz para la pérdida de peso y la mejoría de las comorbilidades a largo plazo. Aunque los estudios demuestran que la cirugía bariátrica es efectiva para el tratamiento del HGNA, la mayoría de los mecanismos implicados en esta mejoría se desconocen. De hecho, las guías clínicas son ambiguas en cuanto a su indicación. Esta revisión tiene como objetivo actualizar la relación entre el HGNA y la cirugía bariátrica, centrándose en las indicaciones de la cirugía y los mecanismos implicados en la mejoría del HGNA. (AU)

Prevalence and predictors of non-alcoholic steatohepatitis in patients with morbid obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.

Bariatric surgery and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that may lead to cirrhosis and hepatocellular carcinoma; its close relationship with obesity and the metabolic syndrome involves an increasing prevalence. Invasive liver biopsy is the gold standard diagnosis technique for NAFLD but entails risks. Therefore, transient elastography, a non-invasive technique with high reliability, is frequently used in clinical practice. Bariatric surgery is the only effective treatment for long-term weight loss and obesity-related metabolic conditions improvement. Although studies report encouraging results of bariatric surgery as a valuable therapy for NAFLD, guidelines for its use in NAFLD are ambiguous. Indeed, the mechanisms driving this improvement are largely unknown, but likely involve weight loss-dependent and independent factors including anatomic and hormonal changes. This review aims to update the relationship between NAFLD and bariatric surgery, focusing on the indications for surgery and the mechanisms implied in NAFLD improvement.

Clinical-biochemical and Fibroelastometric Results of the Mare's Milk Application in Non-Alcoholic Steathepatitis / Resultados clínico-bioquímicos y fibroelastométricos de la aplicación de la leche de yegua en la esteatohepatitis no alcohólica

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, representing the hepatic component of metabolic syndrome, and currently affects an average of 20-33 percent of the adult population. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD and is a consequence of overweight, obesity, and metabolic syndrome. Objective: The study aimed to evaluate the effectiveness of the use of freeze-dried mare's milk in NASH. Methods: Clinical-biochemical, ultrasound, and fibroelastometric research methods were used in NASH patients receiving mare's milk in comparison with the control groups. Results: The result of the study demonstrates noticeable gain not only in the clinical symptoms of the disease but also in the laboratory and instrumental indicators, as well as health improvement and a decrease in symptoms of concomitant pathology. Taking mare's milk not only normalized liver biochemical parameters but also decreased cholesterol metabolism (total cholesterol, LDL, TG), the degree of liver steatosis, and existing hepatomegaly declined too. This pleiotropic effect of mare's milk points to the pathogenetic feasibility for the use of Saumal in NAFLD, including NASH. Conclusions: Addressing the problems of healthy nutrition in NASH, mare's milk can be considered as a pathogenetically justified, highly effective, and affordable natural therapeutic and prophylactic agent. The value of the product is determined by its multicomponent balanced qualitative composition. Hepatoprotective, hypocholesterolemic, and lipotropic properties of mare's milk in this pathology are marked(AU)

Introducción: La enfermedad del hígado graso no alcohólico es la enfermedad hepática más común en el mundo, representa el componente hepático del síndrome metabólico y actualmente afecta a un promedio de 20 a 33 por ciento de la población adulta. La esteatohepatitis no alcohólica es una forma grave de hígado graso no alcohólico y es una consecuencia del sobrepeso, la obesidad y el síndrome metabólico. Objetivo: Evaluar la efectividad del uso de leche de yegua liofilizada en hígado graso no alcohólico. Métodos: Se utilizaron métodos de investigación clínico-bioquímicos, ecográficos y fibroelastométricos en pacientes con hígado graso no alcohólico que recibieron leche de yegua en comparación con los grupos de control. Resultados: El resultado del estudio demuestra una ganancia notable no solo en los síntomas clínicos de la enfermedad, sino también en los indicadores de laboratorio e instrumentales, así como una mejora de la salud y una disminución de los síntomas de la enfermedad concomitante. La ingesta de leche de yegua no solo normalizó los parámetros bioquímicos del hígado, sino que también disminuyó el metabolismo del colesterol (colesterol total, LDL, TG), el grado de esteatosis hepática y la hepatomegalia existente también disminuyeron. Este efecto pleiotrópico de la leche de yegua apunta a la viabilidad patogénica del uso de Saumal en hígado graso no alcohólico, incluida la esteatohepatitis no alcohólica. Conclusión: Al abordar los problemas de una nutrición saludable en la enfermedad hígado graso no alcohólico, la leche de yegua se puede considerar como un agente terapéutico y profiláctico natural patogénicamente justificado, altamente efectivo y asequible. El valor del producto está determinado por su composición cualitativa equilibrada multicomponente. Las propiedades hepatoprotectoras, hipocolesterolémicas y lipotrópicas de la leche de yegua en esta enfermedad son marcadas(AU)

Evaluación de la fibrogénesis hepática en pacientes con esteatohepatitis no alcohólica tratados con propóleos rojo oral cubano / Evaluation of hepatic fibrogenesis in patients with nonalcoholic steatohepatitis treated with cuban oral red propolis

Introducción: La enfermedad por depósito graso no alcohólica constituye una pandemia del mundo contemporáneo. Su espectro silente atraviesa estadios de cronicidad y puede llegar a la cirrosis hepática y sobre esta pudiera desarrollarse un hepatocarcinoma. No existen tratamientos y solo se puede actuar sobre los factores de riesgo. Objetivo: Evaluar el efecto citohepatoprotector y antifibrótico del propóleos rojo cubano oral en pacientes con esteatohepatitis no alcohólica. Métodos: Se realizó un estudio longitudinal prospectivo en pacientes seleccionados de las consultas de Gastroenterología, Endocrinología y Medicina Interna del Hospital Clínico Quirúrgico Hermanos Ameijeiras durante el periodo de abril 2017 a abril 2018. El universo de estudio fue de 120 pacientes con diagnóstico imagenológico de hígado graso. La muestra quedó conformada por 70 pacientes con diagnóstico de hígado graso, y que cumplieron criterios de inclusión y exclusión. Las pruebas estadísticas aplicadas fueron análisis de frecuencia y porcentaje para las variables demográficas. La prueba T para las muestras relacionadas evaluó el comportamiento enzimático al inicio y al final del tratamiento y los cambios elastográficos fueron analizados mediante test de Kappa y porcentaje. Resultados: Las variables bioquímicas estudiadas mostraron una disminución estadísticamente significativa al final del tratamiento. Los cambios elastográficos al final del estudio evidenciaron la efectividad del tratamiento, en el cual el 91,4 por ciento de los pacientes evolucionaron hacia el menor grado de fibrosis. Conclusiones: El propóleos rojo cubano demostró ser un apifármaco con acción citohepatoprotectora y antifibrótica de valor terapéutico(AU)

Introduction: Nonalcoholic fat deposition disease is a pandemic in the contemporary world. Its silent spectrum goes through stages of chronicity and it can reach liver cirrhosis and on this a hepatic carcinoma could develop. There are no treatments and medical handling can act on only risk factors. Objective: To evaluate cytohepatoprotective and antifibrotic effect of oral Cuban red propolis in patients with nonalcoholic steatohepatitis. Methods: A prospective longitudinal study was carried out in selected patients from the Gastroenterology, Endocrinology and Internal Medicine consultations at Hermanos Ameijeiras Clinical Surgical Hospital from April 2017 to April 2018. The study universe was 120 patients with imaging diagnosis of fatty liver. The sample consisted of 70 patients with fatty liver diagnosis, who met the inclusion and exclusion criteria. Frequency and percentage analysis for the demographic variables were the statistical tests applied. The T test for the related samples evaluated the enzymatic behavior at the beginning and at the end of the treatment and the elastography changes were analyzed using Kappa and percentage tests. Results: The biochemical variables studied showed statistically significant decrease at the end of the treatment, which evidenced the effectiveness of the treatment. 91.4 percent of the patients progressed to a lower degree of fibrosis. Conclusions: Cuban red propolis proved to be a therapeutic drug with cytohepathoprotective and antifibrotic action(AU)

Prevalence and predictors of non-alcoholic steatohepatitis in patients with morbid obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.

Silencing HIF-1α aggravates non-alcoholic fatty liver disease in vitro through inhibiting PPAR-α/ANGPTL4 singling pathway / El silenciamiento de HIF-1α agrava la esteatohepatitis no alcohólica in vitro a través de la inhibición de la vía de señalización PPAR-α/ANGPTL4

Objective: Non-alcoholic fatty liver disease (NAFLD) is an aberrant lipid metabolism disease. Hypoxia inducible factor-1 (HIF-1α) is a transcription factor which plays an important part in adapting lower oxygen condition. Here, we aimed to clarify the relationship between HIF-1α and NAFLD. Methods: HepG2 cells was stimulated by oleic acid (OA) and palmitic acid (PA) to establish in vitro model of NAFLD. The expression of lipid metabolism-related genes, the binding of PPARα to HIF-1α promoter, the lipid deposition, and oxidative stress were detected by qRT-PCR, western blot, Chip assay, Oil Red O staining and ELISA assays, respectively. Results: HIF-1α silence promoted lipid accumulation in NAFLD cells, accompanying by the significantly increased contents of TG (triglyceride) and ApoB (apolipoprotein B). In HepG2 cells treated with OA/PA, the expression of lipid metabolism-related genes and proteins, including APOE, A2m, TNFRSF11B, LDLr, and SREBP2, and the intracellular lipid deposition were up-regulated and further aggravated after silencing HIF-1α. In addition, the loss of HIF-1α could remarkably elevate MDA contents while inhibit the activities of beneficial antioxidant enzymes SOD and GSH-Px to activate oxidative stress, and promote the secretion of pro-inflammatory IL-6 and TNF-α to aggravate inflammation in NDFLD cells. PPARα positively bound to HIF-1α promoter. The silence of PPARα aggravated lipid deposition under normal or hypoxic environment in NAFLD cells. In addition, PPAR-α silence could decrease the expression of HIF-1α and ANGPTL4 in NAFLD cell model; moreover, the expression of APOE, A2m and TNFRSF11B and the production of TG and MDA were increased by PPAR-α suppression. Conclusion: HIF-1α plays a crucial role in the regulation of lipid metabolism through activating PPAR-α/ANGPTL4 signaling pathway in NAFLD.(AU)

Objetivo: La esteatohepatitis no alcohólica (EHNA) es una enfermedad del metabolismo aberrante de los lípidos. El factor inducible por hipoxia 1 (HIF-1α) es un factor de transcripción que desempeña una función importante en la adaptación de la afección de nivel de oxígeno bajo. En el presente documento, intentamos aclarar la relación entre HIF-1α y la EHNA. Métodos: Las células HepG2 se estimularon con ácido oleico (OA) y ácido palmítico (PA) para establecer un modelo in vitro de la EHNA. La expresión de los genes relacionados con el metabolismo de los lípidos, la unión de PPARα al promotor HIF-1α, el depósito de lípidos y el estrés oxidativo se detectaron mediante ensayos de qRT-PCR, inmunoelectrotransferencia, ensayo de inmunoprecipitación de cromatina (ChIP), ensayos de tinción de rojo aceite O y ELISA, respectivamente. Resultados: El silencio de HIF-1α promovió la acumulación de lípidos en las células de la EHNA, acompañada de un aumento significativo del contenido de triglicéridos (TG) y apolipoproteína B (ApoB). En las células HepG2 tratadas con OA/PA, la expresión de genes y proteínas relacionados con el metabolismo lipídico, incluidos APOE, A2m, TNFRSF11B, LDLr y SREBP2, y el depósito de lípidos intracelular se regularon al alza y se agravaron aún más después de silenciar HIF-1α. Además, la pérdida de HIF-1α podría elevar notablemente el contenido de MDA e inhibir las actividades de las enzimas antioxidantes beneficiosas SOD y GSH-Px para activar el estrés oxidativo, y promover la secreción de IL-6 pro-inflamatoria y TNF-α para agravar la inflamación en las células de la EHNA. PPARα se unió positivamente al promotor HIF-1α. El silencio de PPARα agravó el depósito de lípidos en un ambiente normal o hipóxico en las células de la EHNA. Además, el silencio de PPAR-α pudo disminuir la expresión de HIF-1α y ANGPTL4 en el modelo de células de la EHNA; por otra parte, la expresión de APOE, A2m y TNFRSF11B, y la producción de TG y MDA aumentaro,

Clinical utility of transient elastography as an imaging tool to assess the short-term impact of laparoscopic sleeve gastrectomy, together with clinical and biochemical parameters and clinico-biochemical indices, on obese patients with nonalcoholic fatty liver disease: An Egyptian pilot study. / La utilidad clínica de la elastografía transitoria como una herramienta de imagenología para evaluar el impacto a corto plazo de la gastrectomía laparoscópica en manga, en conjunto con parámetros clínicos y bioquímicos e índices clínico-bioquímicos en pacientes con enfermedad de hígado graso no alcohólico: un estudio piloto egipcio.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder commonly attributed to fatty acid deposition that can induce hepatic necroinflammation, defined as nonalcoholic steatohepatitis (NASH). It is strongly associated with obesity. Laparoscopic sleeve gastrectomy (LSG) is a favorable surgical modality for the treatment of morbid obesity. AIM: Our study evaluated the impact of LSG on patients with NAFLD and morbid obesity, 3 months after the operation, through clinical and biochemical characteristics, clinico-biochemical indices, and imaging parameters. PATIENTS AND METHODS: Morbidly obese patients with NAFLD±NASH underwent LSG. They were thoroughly evaluated clinically (body weight, body mass index, waist circumference) and biochemically (transaminases and triglycerides), as well as through the fatty liver index (FLI), the hepatic steatosis index (HSI), and ultrasound elastography imaging studies (liver stiffness measurement [LSM] and the controlled attenuation parameter [CAP]), before and 3 months after the LSG. RESULTS: Twenty-six obese patients with NAFLD underwent LSG that resulted in a significantly high reduction in all the parameters analyzed, except for liver transaminases. CONCLUSION: LSG is considered an efficient surgical modality for the treatment of morbidly obese patients with NAFLD.

Silencing HIF-1α aggravates non-alcoholic fatty liver disease in vitro through inhibiting PPAR-α/ANGPTL4 singling pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an aberrant lipid metabolism disease. Hypoxia inducible factor-1 (HIF-1α) is a transcription factor which plays an important part in adapting lower oxygen condition. Here, we aimed to clarify the relationship between HIF-1α and NAFLD. METHODS: HepG2 cells was stimulated by oleic acid (OA) and palmitic acid (PA) to establish in vitro model of NAFLD. The expression of lipid metabolism-related genes, the binding of PPARα to HIF-1α promoter, the lipid deposition, and oxidative stress were detected by qRT-PCR, western blot, Chip assay, Oil Red O staining and ELISA assays, respectively. RESULTS: HIF-1α silence promoted lipid accumulation in NAFLD cells, accompanying by the significantly increased contents of TG (triglyceride) and ApoB (apolipoprotein B). In HepG2 cells treated with OA/PA, the expression of lipid metabolism-related genes and proteins, including APOE, A2m, TNFRSF11B, LDLr, and SREBP2, and the intracellular lipid deposition were up-regulated and further aggravated after silencing HIF-1α. In addition, the loss of HIF-1α could remarkably elevate MDA contents while inhibit the activities of beneficial antioxidant enzymes SOD and GSH-Px to activate oxidative stress, and promote the secretion of pro-inflammatory IL-6 and TNF-α to aggravate inflammation in NDFLD cells. PPARα positively bound to HIF-1α promoter. The silence of PPARα aggravated lipid deposition under normal or hypoxic environment in NAFLD cells. In addition, PPAR-α silence could decrease the expression of HIF-1α and ANGPTL4 in NAFLD cell model; moreover, the expression of APOE, A2m and TNFRSF11B and the production of TG and MDA were increased by PPAR-α suppression. CONCLUSION: HIF-1α plays a crucial role in the regulation of lipid metabolism through activating PPAR-α/ANGPTL4 signaling pathway in NAFLD.