Association between physical exercise and non-alcoholic fatty liver disease in people infected with hepatitis B virus / 中华流行病学杂志

Objective: To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods: The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results: A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m2 (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions: Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to develop an artificial neural network (ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease (NAFLD) in American adults.@*METHODS@#Data from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) 2007-2014 were analyzed. Eligible subjects ( n = 6,613) were randomly divided into a training set ( n 1 = 4,609) and a validation set ( n 2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.@*RESULTS@#Our study found that the odds ratios ( ORs) and 95% confidence intervals ( CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake (i.e., provitamin A carotenoids, such as β-carotene) ( OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.@*CONCLUSION@#The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.

Niveles tensionales en niños y adolescentes con esteatosis hepática / Tensional levels in children and adolescents with hepatic steatosis

Introducción: la enfermedad hepática no alcohólica (EHNA) constituye un desorden multifactorial cuyos elementos de riesgo se pueden aludir a la obesidad, el sedentarismo y el componente genético. Objetivo: evaluar los niveles tensionales en niños y adolescentes con esteatosis hepática por sonografía de 5-18 años en el Hospital Regional Universitario Dr. Arturo Gullón. Métodos y técnicas: se realizó un estudio descriptivo de corte transversal y fuente primaria. La muestra estuvo compuesta por de 106 participantes. Se realizó sonografía abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica y diastólica, IMC, talla y pruebas de laboratorio. Para el análisis estadístico se empleó chi-cuadrado. Resultados: el sexo predominante en la tensión arterial sistólica fue el femenino con un 44.9 % en estadio prehipertensión, mientras que el masculino fue el sexo predominante en presión arterial diastólica con un 49.1 %. Se evidenció que los individuos con IMC del percentil 90 se encontraban en estadio prehipertensión en el percentil. El perfil lipídico (colesterol, HDL, LDL, triglicéridos) y las transaminasas (SGOT y SGPT) mostraron relación con niveles tensionales elevados con predominio en la TAD. Los valores elevados de glicemia presentan relación con las cifras aumentadas de la tensión arterial sistólica. Conclusión: el estudio mostró que existe una relación entre la esteatosis hepática no alcohólica y el riesgo de desarrollar hipertensión arterial. Presentando relación estadísticamente significativa entre los niveles tensionales elevados y el perfil bioquímico estudiado, así como al IMC de los pacientes evaluados en la investigación

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disorder whose risks factors can be attributed to obesity, sedentary lifestyle and a genetic component. Objective: To evaluate blood pressure levels in children and adolescent aged 5-18 years old with hepatic steatosis using ultrasound at the Dr. Arturo Grullón Regional University Hospital. Methods and Techniques: A descriptive cross-sectional study of primary source were carried out. The sample of the study consisted in 106 participants. Abdominal ultrasono-graphy was performed to determine the presence of hepatic steatosis and systolic and diastolic blood pressure, BMI, height and laboratory tests were measured. Chi square was used in the statistical analysis of the data. Results: The predominant sex in systolic blood pressure was female with 44.9% in prehypertension stage, while male was the predominant sex in diastolic blood pressure with 49.1%. It was evidenced that individuals with BMI ≥90thpercentile were in the prehypertensive stage at the percentile. The lipid profile (cholesterol, HDL-C, LDL-C, triglycerides) and transaminases (SGOT ad SGPT) showed a relationship with high blood pressure levels with a predo-minance in DBP. Elevated glucose levels are related to an increase in systolic blood pressure. Conclusion: The study showed that there is a relationship between nonalcoholic fatty liver disease and the risk of developing high blood pressure. Presenting a statistically significant relationship between the elevated blood pres-sure levels and the biochemical profile studied, as well the BMI of the patients evaluated in this research

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study

Abstract BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

Association between neck circumference and non-alcoholic fatty liver disease: cross-sectional analysis from ELSA-Brasil

Abstract BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a public health problem worldwide. Neck circumference (NC) is a simple anthropometric adiposity parameter that has been correlated with cardiometabolic disorders like NAFLD. OBJECTIVES: To investigate the association between NC and NAFLD, considering their obesity-modifying effect, among participants from the Longitudinal Study of Adult Health (ELSA-Brasil) baseline study. DESIGN AND SETTINGS: Cross-sectional study at the ELSA-Brasil centers of six public research institutions. METHODS: This analysis was conducted on 5,187 women and 4,270 men of mean age 51.8 (± 9.2) years. Anthropometric indexes (NC, waist circumference [WC] and body mass index [BMI]), biochemical and clinical parameters (diabetes, hypertension and dyslipidemia) and hepatic ultrasound were measured. The association between NC and NAFLD was estimated using multinomial logistic regression, considering potential confounding effects (age, WC, diabetes, hypertension and dyslipidemia). Effect modification was investigated by including the interaction term NC x BMI in the final model. RESULTS: The frequency of NAFLD and mean value of NC were 33.6% and 33.9 (± 2.5) cm in women, and 45.8% and 39.4 (± 2.8) cm in men, respectively. Even after all adjustments, larger NC was associated with a greater chance of moderate/severe NAFLD (1.16; 95% confidence interval [CI] for women; 1.05, 95% CI for men; P < 0.001). Presence of multiplicative interaction between NC and BMI (P < 0.001) was also observed. CONCLUSION: NC was positively associated with NAFLD in both sexes, regardless of traditional adiposity indexes such as BMI and WC. The magnitude of the association was more pronounced among women.

The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis / 中华预防医学杂志

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

A cohort study on the correlation between alanine aminotransferase trajectories and new-onset metabolic fatty liver disease / 中华流行病学杂志

Objective: To explore the correlation between alanine aminotransferase (ALT) trajectories and new-onset metabolic fatty liver disease (MAFLD) to provide a scientific basis for the prevention and treatment of MAFLD. Methods: The study cohort was composed of 3 553 subjects who met the inclusion criteria in the cohort study of the Henan physical examination population. According to the ALT levels of the subjects' physical examination from 2017-2019, three different ALT trajectory groups were determined by R LCTMtools, namely low-stable group, medium-stable group, and high-stable group. The incidence of MAFLD during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product-limit method, and Cox proportional hazards regression model analyzed the correlation between different ALT trajectories and new-onset MAFLD. Results: The incidence rate of MAFLD parallelly increased with the increase of ALT locus, which was 6.93%, 15.42%, and 19.05%, respectively, and the difference was statistically significant (P<0.001). After adjusting for multiple confounding factors, such as gender, waist circumference, blood pressure, BMI, fasting blood sugar, and blood lipid by Cox proportional hazards regression model, the risks of MAFLD in ALT medium-stable and the high-stable group were still 1.422 times (95%CI:1.115-1.813) and 1.483 times (95%CI:1.040-2.114) of low-stable ALT group (P<0.05). Conclusions: The risk of MAFLD parallelly increases with the increase of ALT level in the normal long-term range. it is necessary to carry out the intervention for MAFLD with long-term average high value to avoid the progress of MAFLD disease to achieve the early prevention on MAFLD.

Study on the relationship between nonalcoholic fatty liver disease and hepatocellular carcinoma in patients with prior hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of nonalcoholic fatty liver disease (NAFLD) in the development of hepatocellular carcinoma (HCC) in patients with prior hepatitis B virus infection (HBsAg-negative and anti-HBC-positive). Methods: 1605 hospitalized patients who were first diagnosed with HCC at Nanfang Hospital between 2015 to 2017 were retrospectively studied. Patients who developed HCC on the basis of active HBV infection (HBsAg-positive, anti-HBc positive) were used as control. Multivariate logistic regression model was used to analyze the relationship between NAFLD and HCC in patients with prior hepatitis B virus infection. Results: Among HCC patients with both HBsAg and anti-HCV negative, the proportion of prior HBV infection accounted for 86.7%. NAFLD prevalence was higher in patients with HCC based on prior HBV infection than active HBV infection (19.7% vs. 8.5%, P < 0.001). After adjusting for gender, age, hypertension, alanine aminotransferase, and liver cirrhosis, patients with HCC based on prior HBV infection were more likely to develop NAFLD (OR: 2.29, 95% CI: 1.40-3.74), and this phenomenon was observed only in patients with non-cirrhosis (OR: 5.26, 95% CI: 2.53-10.96) and aged≥50 years (OR: 2.36, 95% CI: 1.33-4.20). Conclusion: NAFLD may be a risk factor for HCC in a previously infected patients with HBV, especially in non-cirrhotic and population aged≥50 years.

Nonalcoholic fatty liver disease and liver transplantation / 中华肝脏病杂志

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is now the second largest indication for liver transplantation in Western countries, but viral hepatitis B and end-stage alcohol-related liver disease are still the main indications in China. With the improvement of people's living standards, the prevalence of metabolic syndrome, and the number of NAFLD patients has also gradually increased. At the same time, with the hepatitis B vaccination popularization and the nucleos(t)ide analogues and other drugs uses, it is predicted that NAFLD-related end-stage liver disease may become one of the main indications for liver transplantation in our country in the future. This article reviews the research progress of NAFLD and liver transplantation.

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)

Caracterización clinicoepidemiológica de pacientes con enfermedad hepática grasa no alcohólica / Clinical epidemiological characterization of patients with non alcoholic fatty hepatic disease

Introducción: La enfermedad hepática grasa no alcohólica se caracteriza por un aumento de la acumulación de lípidos (triglicéridos) de forma macrovesicular, en más de 5 % de los hepatocitos, asociado o no a inflamación y/o fibrosis hepática. Objetivo: Caracterizar a pacientes con enfermedad hepática grasa no alcohólica según variables de interés para el estudio. Método: Se realizó un estudio descriptivo y transversal de 95 pacientes atendidos en el Servicio de Gastroenterología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde junio hasta diciembre de 2018. Entre las variables figuraron: edad, sexo, factores de riesgo, resultados de exámenes complementarios, ecografía hepática y factores de pronósticos clínicos para la fibrosis. Resultados: En la serie predominaron los grupos etarios de 35-44 y de 45-54 años (65,2 %, respectivamente), el sexo femenino, la obesidad como principal factor de riesgo (50,5 %), la transaminasa glutámico pirúvica-alanina aminotransferasa (39,0 %) entre los exámenes complementario con valores alterados y la esteatosis hepática moderada como hallazgo ecográfico (55,8 %), entre otros. Conclusiones: La enfermedad hepática grasa no alcohólica prevaleció en los pacientes entre 35-54 años, donde la obesidad constituyó el factor de riesgo más importante; asimismo, un mayor número de pacientes presentó cifras elevadas de transaminasa glutámico pirúvica-alanina aminotransferasa y los hallazgos ecográficos revelaron la primacía de la esteatosis moderada. La presencia de 4 o más factores pronósticos constituyó un riesgo para el desarrollo de fibrosis hepática.

Introduction: The non alcoholic fatty hepatic disease is characterized by an increase of the lipids accumulation (triglycerides) in a macrovesicular way, in more than 5 % of the hepatic cells, associated or not with inflammation and/or hepatic fibrosis. Objective: To characterize patients with non alcoholic fatty hepatic disease according to variables of interest for the study. Method: A descriptive and cross-sectional study of 95 patients assisted in the Gastroenterology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital was carried out in Santiago de Cuba, from June to December, 2018. Among the variables figured: age, sex, risk factors, results of complementary exams, hepatic echography and clinical prognosis factors for the fibrosis. Results: In the series there was a prevalence of the 35-44 and 45-54 age groups (65.2 %, respectively), female sex, obesity as main risk factor (50.5 %), transaminase glutamic piruvic-alanineaminotransferase (39.0 %) among the complementary exams with altered values and the moderate fatty liver as echographic finding (55.8 %), among others. Conclusions: The non alcoholic fatty hepatic disease prevailed in patients between 35-54 years, where obesity constituted the most important risk factor; also, a greater number of patients presented high figures of transaminase glutamic piruvic-alanineaminotransferase and the echographic findings revealed the primacy of the moderate steatosis. The presence of 4 or more prognosis factors constituted a risk for the development of hepatic fibrosis.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999-2016 / 中华医学杂志(英文版)

BACKGROUND@#Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation.@*RESULTS@#The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD.@*CONCLUSIONS@#From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

The association between urinary bisphenol A levels and nonalcoholic fatty liver disease in Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017

BACKGROUND@#Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD.@*METHODS@#The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases.@*RESULTS@#There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively.@*CONCLUSIONS@#Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

Is there a link between non-alcoholic fatty liver disease aspects and pancreatic cancer? Results of a case-matched study / Existe ligação entre a doença hepática gordurosa não alcoólica e o câncer de pâncreas? Resultados de estudo caso-controle

ABSTRACT Background and Aims: An association between non-alcoholic fatty liver disease (NAFLD) and pancreatic ductal adenocarcinoma (PDAC) has been previously suggested. This study aims at investigating this association and at identifying potential links between variables of the NAFLD spectrum and PDAC. Methods: A cross-sectional case-matched analytical and comparative study was carried out to analyze patients undergoing surgical resection of PDAC and compare them to a control group of individuals undergoing cholecystectomy at a public tertiary teaching hospital, matched by sex, age and BMI. Hepatic histopathological examinations were compared between cases and controls. Results: Of 56 individuals, 36 were male (64.3%) and the median age was 61.5 years old (interquartile range: 57.5 - 70). The participants' median BMI was 24.3 kg/m2 (interquartile range: 22.1-26.2 kg/m2). Microvesicular steatosis (p=0.04), hepatocellular ballooning (p=0.02), fibrosis (p=0.0003) and steatohepatitis (p=0.03) were significantly more frequent in the group of cases. Odds ratios for hepatocellular ballooning (6.2; 95%CI: 1.2-31.8; p=0.03), fibrosis (9.3; 95%CI: 2.5-34.1; p=0.0008) and steatohepatitis (3.9; 95%CI: 1.1-14.3; p=0.04) were statistically significant in relation to the PDAC prevalence. Conclusions: Significant associations were identified between histopathological aspects of NAFLD (microvesicular steatosis, hepatocellular ballooning, fibrosis, and steatohepatitis) and PDAC.

RESUMO Histórico e objetivos: a associação entre a doença hepática gordurosa não alcoólica (DHGNA) e o adenocarcinoma ductal pancreático (ACDP) foi sugerida anteriormente. Este estudo visa investigar esta associação e identificar possíveis ligações entre as variáveis do espectro da DHGNA e o ACDP. Métodos: foi realizado estudo transversal caso-controle analítico e comparativo para analisar pacientes submetidos a ressecção cirúrgica de ACDP e compará-los a grupo controle de indivíduos submetidos a colecistectomia em hospital público terciário de ensino, pareados por sexo, idade e IMC. Os exames histopatológicos hepáticos foram comparados entre casos e controles. Resultados: dos 56 indivíduos, 36 eram do sexo masculino (64,3%) e a idade mediana era de 61,5 anos de idade (intervalo interquartil 57,5-70). A mediana do IMC dos participantes foi de 24,3 kg/m2 (intervalo interquartil 22,1 26,2). Esteatose microvesicular (p = 0,04), balonização hepatocelular (p = 0,02), fibrose (p = 0,0003) e esteato-hepatite (p = 0,03) foram significativamente mais frequentes no grupo de casos. As razões de chances para balonização hepatocelular (6,2; IC 95%: 1,2 - 31,8; p = 0,03), fibrose (9,3; IC 95%: 2,5 - 34,1; p = 0,0008) e esteato-hepatite (3,9; IC 95%: 1,1 - 14,3; p = 0,04) foram estatisticamente significativas em relação à prevalência de ACDP. Conclusões: houve associações significativas entre aspectos histopatológicos de DHGNA (esteatose microvesicular, balonização hepatocelular, fibrose e esteato-hepatite) e a ocorrência de ACDP.

Investigación traslacional en microbioma (InTraMic): un área de interés común y creciente en el IMTIB, Hospital Italiano e Instituto Universitario / Translational research in microbiome (InTraMic): an area of common and growing interest at IMTIB, Hospital Italiano and Instituto Universitario

Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)

It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)

Non-alcoholic fatty liver disease in patients infected with human immunodeficiency virus: a systematic review

SUMMARY OBJECTIVE To evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with HIV/AIDS. METHODS The systematic review included articles indexed in MEDLINE (by PubMed), Web of Science, IBECS, and LILACS. Studies eligible included the year of publication, diagnose criteria of NAFLD and HIV, and were published in English, Portuguese, or Spanish from 2006 to 2018. The exclusion criteria were studies with HIV-infection patients and other liver diseases. Two reviewers were involved in the study and applied the same methodology, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). RESULTS One hundred and sixteen papers were selected, including full articles, editorial letters, and reviews. Twenty-seven articles were excluded because they did meet the inclusion criteria. A total of 89 articles were read, and 13 were considered eligible for this review. Four case series used imaging methods to identify NAFLD, and nine included histology. The prevalence of NAFLD in HIV-patients ranged from 30%-100% and, in nonalcoholic steatohepatitis (NASH), from 20% to 89%. A positive association between dyslipidemia, insulin resistance, and body mass index was observed. There was no agreement between the studies that evaluated the relationship between antiretroviral drugs and NAFLD. CONCLUSION This systematic review showed a high prevalence of NAFLD in HIV-patients, which was associated with metabolic risk factors. The possible association between antiretroviral therapy and NAFLD needs further studies.

RESUMO OBJETIVO Avaliar a relevância da doença hepática gordurosa não alcoólica (DHGNA) em pacientes com HIV / AIDS. MÉTODOS A revisão sistemática foi realizada utilizando instrumentos de busca de material científico indexado, incluindo MEDLINE (pela PubMed), Web of Science, IBECS e LILACS. Estudos elegíveis incluíram o ano de publicação, critérios para diagnostico de DHGNA e HIV, publicados em inglês, português e espanhol, entre 2006 a 2018. Os critérios de exclusão incluíram estudos com pacientes com outras doenças do fígado. Dois revisores foram envolvidos na pesquisa dos artigos e o PRISMA (Preferred Reporting Items for Systematic Reviews and Meta - Analyses) foi utilizado nas análises. RESULTADOS Cento e dezesseis artigos foram selecionados, 27 excluídos porque não preencheram critérios de inclusão e assim, 89 foram lidos pelos investigadores. Desses, 13 artigos foram incluídos na revisão. Quatro séries de casos utilizaram métodos por imagens para identificação de DHGNA e nove estudos utilizaram biópsia hepática. A prevalência de DHGNA em pacientes com HIV variou de 30% a 100% e esteato-hepatite não alcoólica (EHNA) entre 20% e 89%. Na avaliação das principais variáveis estudadas, observou-se a associação positiva entre dislipidemia, resistência à insulina e índice de massa corporal. Não houve concordância entre os artigos que avaliaram a relação dos antiretrovirais com a DHGNA. CONCLUSÕES A presente revisão sistemática sugere elevada prevalência de DHGNA em pacientes infectados com HIV. DHGNA nesses pacientes foi associada principalmente a fatores metabólicos. A possível associação entre terapia antiretroviral e DHGNA nesses pacientes vem sendo discutida, mas são necessários mais estudos para estabelecer essa associação.

MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy / 中华医学杂志(英文版)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, placing an increasing burden on human health. NAFLD is a complex multifactorial disease involving genetic, metabolic, and environmental factors. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes, of which insulin resistance is the main pathophysiological mechanism. Over the past few decades, investigation of the pathogenesis, diagnosis, and treatments has revealed different aspects of NAFLD, challenging the accuracy of definition and therapeutic strategy for the clinical practice. Recently, experts reach a consensus that NAFLD does not reflect the current knowledge, and metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested as a more appropriate term. The new definition puts increased emphasis on the important role of metabolic dysfunction in it. Herein, the shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy of the newly defined MAFLD, as compared with the formerly defined NAFLD, are reviewed for updating our understanding.

Enfermedades hepáticas y su relación con hiperglicemia / The relationship between liver diseases and hyperglycemia

La Diabetes Mellitus tipo 2 (DM2) y las enfermedades crónicas del hígado(ECH), definida para esta revisión como cualquier alteración funcional o estructural de este órgano, desde inflamación hasta fibrosis, son patologías que frecuentemente se asocian, y su coexistencia se relaciona con peor pronóstico y mayores complicaciones de ambas entidades. El objetivo de este artículo es describir la relación entre hiperglicemia y enfermedades del hígado, sus procesos fisiopatológicos comunes y tratamiento, distinguiendo las patologías más relevantes, entre ellas la Diabetes Hepatogénica (DH), la enfermedad hepática por Virus Hepatitis C (VHC) y la Enfermedad Hepática Grasa No Alcohólica (EHGNA). La DH es aquella diagnosticada en pacientes con cirrosis asociada a insuficiencia hepática, sin antecedentes previos de alteración de la glicemia. En la actualidad el diagnóstico se realiza en etapas tardías de la enfermedad. El VHC tiene un efecto diabetogénico conocido. Algunas terapias antivirales usadas para VHC evidencian mejoría de las alteraciones metabólicas al lograr respuestas virológicas sostenidas. En DM2, la EHGNA es frecuente, con mayor incidencia de fibrosis, hepatocarcinoma (HCC) y riesgo cardiovascular (RCV). Es necesario realizar una pesquisa e intervención precoz de EHGNA a los pacientes con DM2. En el manejo de éstos, la baja de peso ha demostrado ser efectiva en el control glicémico y en la mejoría histológica. Dentro de las terapias antidiabéticas, además del uso de metformina, debería considerarse aquellas que han demostrado a la fecha beneficios en EHGNA, como son tiazolidinedionas (pioglitazona) y/o análogos de GLP-1 (liraglutide) y optimizar el control de otros factores de RCV.

Type 2 Diabetes Mellitus (DM2) and chronic liver diseases (CLD) defined in this revision as any functional or structural alteration in the organ, covering from inflammation to fibrosis, are pathologies that are frequently associated, and when found together are related to worse prognosis and higher complications in both conditions. The objective of this article is to describe the relationship between hyperglycemia and liver diseases, their common physio-pathological processes and treatments, identifying the most important pathologies, including Hepatogenic Diabetes (HD), Hepatitis C Virus (HCV) liver disease and Non-Alcoholic Fatty Liver Disease (NAFLD). Hepatogenic diabetes (HD) is diagnosed in patients with liver failure associated to cirrhosis with no previous record of impaired glycemia. Currently, diagnosis is made during the late stages of the disease. Hepatitis C virus (HCV) has a known diabetogenic effect. Some antiviral therapies used for HCV show improvement in metabolic alterations by achieving sustained virological responses. Non-alcoholic fatty liver disease (NAFLD) in DM2 patients is common, presenting higher risk for fibrosis, hepatocellular carcinoma (HCC) and increased cardiovascular risk (CVR). Early screening and interventions for NAFLD in DM patients are necessary. Weight loss has been shown to be effective in glycemic control and histological improvement. Anti-diabetic therapies, in addition to the use of metformin, should consider therapies that have shown benefits for managing NAFLD, such as thiazolidinedione (pioglitazones) and/or aGLP-1 (Liraglutide), and optimally controlling other cardiovascular risk (CVR) factors.

Bypass vs. sleeve and its effects in non-alcoholic fatty liver disease: what is the best technique? / Bypass vs. sleeve e seus resultados na doença hepática gordurosa não alcoólica: qual a melhor técnica?

ABSTRACT Background: Strongly associated with obesity, non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. It presents as simple steatosis and steatohepatitis, which can progress to cirrhosis and its complications. Among the therapeutic alternatives is bariatric surgery. Aim: To compare the effect of the two most frequent bariatric procedures (sleeve and bypass) on liver disease regarding to epidemiological, demographic, clinical and laboratory parameters. Methods: The results of intraoperative and 12 months after surgery liver biopsies were used. The NAFLD activity score (NAS) was used to assess and compare the stages of liver disease. Results: Sixteen (66.7%) patients underwent Bypass procedure and eight (33.3%) Sleeve. It was observed that the variation in the NAFLD activity score was significantly greater in the Bypass group than in Sleeve (p=0.028) and there was a trend regarding the variation in fibrosis (p=0.054). Conclusion: Both surgical techniques were effective in improving the hepatic histology of most operated patients. When comparing sleeve and bypass groups, bypass showed better results, according to the NAS score.

RESUMO Racional: Fortemente associada à obesidade, a doença hepática gordura não alcoólica é considerada a manifestação hepática da síndrome metabólica. Ela apresenta-se como esteatose simples e esteato-hepatite, podendo evoluir para cirrose e suas complicações. Entre as alternativas terapêuticas está a cirurgia bariátrica. Objetivo: Comparar o efeito sobre a doença hepática dos dois procedimentos bariátricos mais frequentes - sleeve e bypass - e comparar dados epidemiológicos, demográficos, parâmetros clínicos e laboratoriais. Métodos: Utilizou-se o resultado das biópsias hepáticas realizadas no intra-operatório e 12 meses após a operação. O NAFLD activity score foi utilizado para avaliar e comparar os estágios da doença hepática. Resultados: Dezesseis (66,7%) pacientes foram submetidos ao bypass e oito (33,3%) ao sleeve. Observou-se melhora significativa no IMC e glicemia nas duas técnicas cirúrgicas enquanto que os níveis de fosfatase alcalina, ferritina, Gama-GT e TGP reduziram com significância apenas no grupo bypass. A redução no NAFLD activity score foi significativamente maior no grupo bypass que no sleeve (p=0,040). Conclusão: Ambas as técnicas foram eficazes em promover a melhora da histologia hepática da maior parte dos pacientes operados. Quando comparadas o bypass apresentou melhores resultados.

Prevalence of hepatic steatosis among children and adolescents with cystic fibrosis and its association with nutritional status / Prevalência de esteatose hepática em crianças e adolescentes com fibrose cística e associação com o estado nutricional

ABSTRACT Objective: To determine the prevalence of hepatic steatosis (HS) in children and adolescents with cystic fibrosis (CF) and associate it with nutritional status. Methods: Cross-sectional study with children and adolescents with CF diagnosis. Weight and height were used to calculate the body mass index (BMI) and subsequent classification of the nutritional status. The midarm circumference (MAC), triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC) were used to evaluate body composition. Abdominal ultrasonography was performed for diagnosis of HS. The statistical tests used were Student's t test, Mann-Whitney test and chi-square test with significance level of 5%. Results: 50 patients with CF were evaluated, 18 (36%) were diagnosed with HS (Group A) and 32 (64%) without HS (Group B). The mean age of Group A was 13,2±4,9 years old and Group B 11,7±4,9; for BMI, the value for Group A was 18,0±4,1 and Group B was 15,7±3,8; the TSF of Group A was 8,4±3,5 mm and Group B was 7,0±2,5 mm. For these variables, there was no significant difference between the groups. The mean of MAC and MAMC differed significantly between the groups, being higher in the HS group, with p values of 0,047 and 0,043. Conclusions: The frequency of HS in patients with CF is high and it is not related to malnutrition, according to the parameters of BMI, TSF and MAMC. The values of MAC and MAMC indicated a greater reserve of muscle mass in patients with HS.

RESUMO Objetivo: Determinar a prevalência de esteatose hepática (EH) em crianças e adolescentes com fibrose cística (FC) e associá-la com o estado nutricional. Métodos: Estudo transversal com crianças e adolescentes com diagnóstico de FC. Foram aferidos o peso e a altura para o cálculo do índice de massa corpórea (IMC) e classificação do estado nutricional. A circunferência do braço (CB), a dobra cutânea tricipital (DCT) e a circunferência muscular do braço (CMB) foram empregadas para avaliação da composição corporal. A ultrassonografia abdominal foi realizada para o diagnóstico de EH. Os testes estatísticos empregados foram o teste t de Student, o teste de Mann-Whitney e o teste do qui-quadrado, com nível de significância de 5%. Resultados: Dos 50 pacientes avaliados, 18 (36%) apresentaram EH (Grupo A) e 32 (64%) não (Grupo B). Para as médias de idade (Grupo A: 13,3±5,0 anos; e Grupo B: 11,7±5,0 anos), IMC (Grupo A: 18,0±4,1; e Grupo B: 15,7±3,8) e DCT (Grupo A: 8,4±3,5 mm; e Grupo B: 7,0±2,5 mm), não houve diferença significativa entre os grupos. A média da CB e da CMB diferiram significativamente entre os grupos, sendo mais elevada no grupo com EH, com valores p respectivos de 0,047 e 0,043. Conclusões: É alta a frequência de EH em pacientes com FC e ela não está relacionada com a desnutrição, segundo os parâmetros de IMC, DCT e CMB. Os valores de CB e CMB indicaram maior reserva de massa muscular nos pacientes com EH.