Alteración de la microbiota intestinal y su relación con enfermedades gastrointestinales y hepatobiliares / Disruption of the intestinal microbiota and its relationship with gastrointestinal and hepatobiliary diseases

La interrupción de la simbiosis que existe entre el cuerpo humano y su microbioma puede resultar en una disbiosis, un desequilibrio en la interacción huésped-microbiota, que puede asociarse al desarrollo de diversas enfermedades como el síndrome de intestino irritable, hígado graso no alco-hólico, enfermedad hepática alcohólica y cirrosis, entre otras. En ciertas condiciones patológicas y por múltiples factores de riesgo, la capacidad de autorregulación del intestino se puede alterar, contribuyendo al incremento de la permeabilidad con inflamación intestinal crónica. El diagnóstico y el tratamiento, así como la relación entre la permeabilidad intestinal, la disbiosis y las patologías gastrointestinales y hepatobiliares, todavía no tienen estudios clínicos validados o con el soporte científico adecuado, por lo que se realiza una revisión de la literatura con la finalidad de aportar conceptos que puedan orientar con respecto a la importancia del estudio del microbioma humano en estas enfermedades.

Disruption of the symbiosis that exists between the human body and its microbiome can result in dys-biosis, an imbalance in the host-microbiota interaction, which may be associated with the develop-ment of various diseases such as irritable bowel syndrome, non-alcoholic fatty liver disease, alcoholic liver disease and cirrhosis, among others. In certain pathological conditions and due to multiple risk factors, the self-regulating capacity of the intestine may be lost, contributing to increased permeability with chronic intestinal inflammation. Its diagnosis and treatment as well as the relationship between intestinal permeability, dysbiosis and gastrointestinal and hepatobiliary pathologies have not been validated in clinical studies or have adequate scientific support, so a review of the literature is carried out in order to provide concepts that can guide with respect to the importance of the study of the human microbiome in these diseases

Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia

ABSTRACT Introduction: We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods: Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results: In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9-34.2, p = 0.004). Conclusions: Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

Nonalcoholic steatohepatitis: An emerging cause of cirrhosis in Colombia / La esteatohepatitis no alcohólica: una causa emergente de cirrosis en Colombia

Abstract Introduction: Cirrhosis of the liver is a significant cause of morbidity and mortality in Latin America; the increased prevalence of metabolic syndrome in our population could be changing the epidemiological profile of patients with advanced chronic liver disease. Aim: To characterize a group of patients with cirrhosis of the liver at an outpatient hepatology care center in Cartagena de Indias, Colombia, and determine the contribution of nonalcoholic steatohepatitis (NASH) as an etiological factor in this population. Materials and methods: Retrospective, cross-sectional, analytical study. All patients who attended the hepatology follow-up with a diagnosis of cirrhosis of the liver were in the six-monthly follow-up protocol that included screening for hepatocellular carcinoma (HCC) and esophageal varices. Results: 346 patients were included, most were women (54.3 %). The first and second causes of cirrhosis were cryptogenic (35 %) and NASH (30.9 %), respectively, followed by viral hepatitis (17 %) and autoimmune diseases (9 %). Of these patients, 87.4 % were within categories A and B of the Child-Turcotte-Pugh score, and only 12.5 % (33 patients) were in stage C. Also, 60 % had at least one clinical decompensation, 38 % a history of variceal hemorrhage, and 4 % a diagnosis of HCC; 80.6 % of patients with NASH cirrhosis had diabetes, and 46.7 % were overweight. Conclusion: NASH cirrhosis is an emerging cause of advanced chronic liver disease in Colombia.

Resumen Introducción: la cirrosis hepática es una importante causa de morbimortalidad en América Latina; el incremento de la prevalencia del síndrome metabólico en nuestra población podría estar cambiando el perfil epidemiológico de los pacientes con enfermedad hepática crónica avanzada. Objetivos: caracterizar un grupo de pacientes con cirrosis hepática y determinar la contribución de la esteatohepatitis no alcohólica (NASH) como factor etiológico de esta población en la ciudad de Cartagena de Indias, Colombia, en un centro de atención ambulatoria de hepatología. Métodos: estudio retrospectivo, transversal, analítico. Se incluyeron todos los pacientes que acudieron al seguimiento de hepatología con diagnóstico de cirrosis hepática que se encontraban en el protocolo de seguimiento semestral que incluía el cribado de hepatocarcinoma y várices esofágicas. Resultados: se incluyeron 346 pacientes. La mayoría fueron mujeres (54,3 %). La primera y segunda causa de cirrosis fue la criptogénica (35 %) y la NASH (30,9 %), respectivamente; seguidas de las hepatitis virales (17 %) y enfermedades autoinmunes (9 %). De estos pacientes, el 87,4 % se encontraba dentro de las categorías A y B de la escala pronóstica de Child-Turcotte-Pugh, y solo el 12,5 % (33 pacientes) en estadio C. El 60 % había presentado al menos una descompensación clínica, 38 % tenía antecedentes de hemorragia por várices y 4 %, diagnóstico de hepatocarcinoma. El 80,6 % de los pacientes con cirrosis NASH era diabético y el 46,7 % tenía exceso de peso. Conclusión: La cirrosis NASH es una causa emergente de enfermedad hepática crónica avanzada en Colombia.

Hepatocellular carcinoma: A real-life experience in a specialized center in Bogotá, Colombia / Hepatocarcinoma: experiencia de la vida real en un centro especializado de Bogotá, Colombia

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.

Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.

The behavior of liver diseases in a cohort of Colombian patients with COVID-19 / Comportamiento de las enfermedades hepáticas en una cohorte de pacientes colombianos con COVID-19

Abstract Introduction: Severe acute respiratory syndrome type 2 coronavirus infection (SARS-CoV-2) is receiving the most attention now. The asymptomatic elevation of transaminases is typical in the liver, and liver involvement varies from 14 % to 78 %. The assessment of liver comorbidities is scarce, with prevalence ranging between 2 % and 11 %. Aim: To describe the behavior of a cohort of patients with liver diseases who fell ill with coronavirus disease 2019 (COVID-19). Materials and methods: This retrospective observational study analyzed the behavior of a cohort of patients with liver diseases who fell ill with COVID-19. Results: 543 patients became ill with COVID-19, of which 300 were women (55.3 %). The median age at diagnosis of liver disease was 52 years. The leading causes of liver disease were nonalcoholic steatohepatitis (49.5 %), cholestatic disease (7.7 %), and hepatitis C and B viruses (6.3 %). Alanine aminotransferase (ALT) had a median of 52 U/L (interquartile range [IQR]: 30-98) and aspartate aminotransferase (AST) 32 U/L (IQR: 23-62). Mortality due to viral infection was 5.7 %, with an incidence rate of 2.9 (95 % confidence interval [CI]: 2-4.2). Conclusions: It is a retrospective study but, until the preparation of the manuscript, it had been the first cohort in Colombia to describe the behavior of liver diseases in patients who become ill with COVID-19. No statistically significant differences were found between the causes of liver disease that confer a higher risk of mortality; however, having decompensated cirrhosis is the only condition related to mortality.

Resumen Introducción: la infección por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) concentra la mayor atención en el momento. En el hígado es frecuente la elevación asintomática de transaminasas y la afectación hepática varía del 14 % al 78 %. La evaluación de las comorbilidades hepáticas es escasa, con prevalencias que oscilan entre el 2 % y el 11 %. Objetivo: describir el comportamiento de una cohorte de pacientes con enfermedades hepáticas que presentaron el coronavirus de 2019 (COVID-19). Materiales y métodos: estudio observacional retrospectivo que analizó el comportamiento de una cohorte de pacientes con hepatopatías que enfermaron por COVID-19. Resultados: 543 pacientes padecieron por COVID-19, de los cuales 300 fueron mujeres (55,3 %). La mediana de edad al diagnóstico de la enfermedad hepática fue de 52 años. Las principales causas de las hepatopatías fueron esteatohepatitis no alcohólica (49,5 %), enfermedad colestásica (7,7 %), virus de la hepatitis C y B (6,3 %). La alanina-aminotransferasa (ALT) presentó una mediana de 52 U/L (rango intercuartílico [RIC]: 30-98) y aspartato-aminotransferasa (AST) 32 U/L (RIC: 23-62). La mortalidad por la infección viral fue del 5,7 % con una tasa de incidencia de 2,9 (intervalo de confianza [IC] 95 %: 2-4,2). Conclusiones: es un estudio de carácter retrospectivo; sin embargo, hasta la elaboración del manuscrito es la primera cohorte en Colombia en describir el comportamiento de las enfermedades hepáticas en pacientes que enferman de COVID-19. No se encontraron diferencias estadísticamente significativas entre las causas de hepatopatía que confieran un mayor riesgo de mortalidad; sin embargo, tener una descompensación de cirrosis es la única condición que tiene una relación con la mortalidad.

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

Métodos no invasivos sobre diagnóstico de esteatosis hepática no alcohólica: descripción de su sensibilidad y especificidad / Noninvasive methods on diagnosis of nonalcoholic hepatic steatosis: description of their sensitivity and specificity / Métodos não invasivos para o diagnóstico de esteatose hepática não alcoólica: descrição de sua sensibilidade e especificidade

El hígado graso no alcohólico es una patología de distribución mundial, siendo su evolución hepática crónica la más común. El objetivo de esta investigación consiste en actualizar y describir la sensibilidad y especificidad de los métodos no invasivos para el diagnóstico de esteatosis hepática priorizando las pruebas bioquímicas utilizadas para NAFLD, aplicando un enfoque de tipo documental a través de revisión sistemática y, empleando como metodología, las normas PRISMA y la herramienta QUADAS-2 para el filtro y selección de artículos. En total, se obtuvieron 441 artículos relacionados al tema de investigación mediante bases de datos como PubMed, Scopus, Web Of Science, Science Direct, Scielo y otros, de los cuales 13 fueron seleccionados. Se encontró que factores relacionados a la presencia o no de comorbilidades como el síndrome metabólico, diabetes, HTA, etnia, peso y raza influyen en la NAFLD; por otro lado, las enzimas hepáticas no son predictores sensibles de la enfermedad. Se evidencia también que la esteatosis hepática está directamente relacionada con el aumento del IMC, triglicéridos, HDL, ALT y GGT.

Non-alcoholic fatty liver disease is a pathology of worldwide distribution, being its chronic hepatic evolution the most common. The research aims to update and describe the sensitivity and specificity of noninvasive methods for the diagnosis of hepatic steatosis, prioritizing the biochemical tests used for NAFLD, applying a documentary approach through a systematic review, and using as methodology the PRISMA standards and the QUADAS-2 tool for the filter and selection of articles. In total, 441 articles related to the research topic were obtained through databases such as PubMed, Scopus, Web of Science, Science Direct, Scielo and others, of which 13 were selected. It was found that factors related to the presence or not of comorbidities such as metabolic syndrome, diabetes, AHT, ethnicity, weight, and race influence NAFLD; on the other hand, liver enzymes are not sensitive predictors of the disease. It is also evidenced that hepatic steatosis is directly related to increased BMI, triglycerides, HDL, ALT and GGT.

O fígado gordo não alcoólico é uma patologia com distribuição mundial, sendo a sua evolução hepática crónica a mais comum. O objetivo desta pesquisa é atualizar e descrever a sensibilidade e especificidade dos métodos não invasivos para o diagnóstico da esteatose hepática, priorizando os exames bioquímicos utilizados para DHGNA, aplicando uma abordagem do tipo documental por meio de revisão sistemática e, utilizando como metodologia, a Normas PRISMA e a ferramenta QUADAS-2 para filtragem e seleção de artigos. No total, 441 artigos relacionados ao tema de pesquisa foram obtidos por meio de bases de dados como PubMed, Scopus, Web Of Science, Science Direct, Scielo e outras, dos quais 13 foram selecionados. Constatou-se que fatores relacionados à presença ou não de comorbidades como síndrome metabólica, diabetes, hipertensão, etnia, peso e raça influenciam a DHGNA; por outro lado, as enzimas hepáticas não são preditores sensíveis de doença. Fica evidente também que a esteatose hepática está diretamente relacionada ao aumento do IMC, triglicerídeos, HDL, ALT e GGT.

Survival in Patients with Cirrhosis According to Etiology. Retrospective Cohort / Sobrevida en pacientes con cirrosis de acuerdo con su etiología. Cohorte retrospectiva

Abstract Introduction: Cirrhosis is the final stage of chronically progressive liver diseases of various etiologies. It is a common disease, with a variable prevalence in each country. Its peak incidence occurs between 40 and 50 years of age, predominantly in men. Aims: To compare a cohort of patients diagnosed with cirrhosis, evaluate their complications and survival according to etiology, describe clinical and laboratory aspects, and determine the role of a fatty liver. Materials and methods: A retrospective cohort study was carried out with patients who held a specialized hepatology consultation in the center of liver and digestive diseases (CEHYD) in Bogotá, Colombia, between January 2010 and June 2019. Results: We reviewed a total of 1,200 medical records (56.8 % women). There were no statistically significant differences in median survival between groups by etiology, sex, presence or absence of complications, or Child. We noted that the older the age at the diagnosis of cirrhosis, the higher the risk of death; HR 1.04 (95 % CI 1.02-1.075). For each month that follow-up increases, the risk of death decreases by 90 %; HR 0.1 (95 % CI 0.03-0.29). For each month that the follow-up of complications increases, the risk of death is reduced by 2 %; HR 0.98 (95 % CI 0.97-0.99). Conclusions: Survival by etiology was similar in the different groups. Nonalcoholic steatohepatitis (NASH) was the leading cause of cirrhosis in this cohort. Efforts should focus on its diagnosis and management in the early stages.

Resumen Introducción: la cirrosis es el estadio final de enfermedades hepáticas crónicamente progresivas de diferentes etiologías. Es una enfermedad frecuente, con una prevalencia variable en cada país. Su pico de incidencia se presenta entre los 40 y 50 años, predominantemente en hombres. Objetivos: comparar una cohorte de pacientes con diagnóstico de cirrosis, evaluar sus complicaciones y sobrevida de acuerdo con su etiología, describir los aspectos clínicos y de laboratorio, y determinar el papel del hígado graso. Materiales y métodos: se realizó un estudio de cohorte retrospectiva, en donde se incluyeron pacientes que asistieron a consulta especializada de hepatología en el centro de enfermedades hepáticas y digestivas (CEHYD), en la ciudad de Bogotá, durante enero de 2010 y junio de 2019. Resultados: se revisaron un total de 1200 historias clínicas (56,8 % mujeres). No se evidenció diferencias estadísticamente significativas en las medianas de sobrevida entre los grupos por etiologías, sexo, presencia o no de complicaciones, o Child. Se evidenció que entre mayor edad en el diagnóstico de cirrosis, el riesgo de muerte es mayor; HR 1,04 (IC 95 % 1,02-1,075). Por cada mes que aumenta el seguimiento se reduce el riesgo de muerte en 90 %; HR 0,1 (IC 95 % 0,03-0,29). Por cada mes que aumenta el seguimiento de las complicaciones se reduce el riesgo de muerte en 2 %; HR 0,98 (IC 95 % 0,97-0,99). Conclusiones: La sobrevida por etiología fue similar en los diferentes grupos. La esteatohepatitis no alcohólica (NASH) fue la principal causa de cirrosis en esta cohorte. Se deben orientar esfuerzos a su diagnóstico y manejo en fases tempranas.

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 prevalence of non-alcoholic fatty liver disease and its association with Glycemic Control in Type 2 Diabetes Mellitus patients at the Batangas Medical Center – Out-patient Department

Background@#Diabetes mellitus is a chronic disease which has been increasing both in incidence and global impact. In the Philippines, cases of diabetes mellitus increase at an alarming rate. Previous study in Nigeria among Type 2 Diabetic patients with non-alcoholic fatty liver disease (NAFLD) has observed an increased prevalence of 69%. However, there is no definite association between severity of NAFLD and glycemic control (HbA1c).@*Objectives@#To investigate the prevalence of NAFLD and its association with glycemic control of Type 2 Diabetes Mellitus (T2DM) patients at Batangas Medical Center (BatMC) – Out Patient Department (OPD).@*Methods@#A single center, cross sectional study was performed on 80 T2DM patients, who underwent OPD consultation between November 2020 to October 2021. Clinicodemographic profile, duration of T2DM, diagnostic tests including HbA1c and ultrasound of the liver were taken. Chi-Square test of homogeneity and Fisher’s Exact test/Fisher-Freeman-Halton test were utilized for comparison of categorical variables from a single population to determine whether there is a significant association between the severity of NAFLD and patients characteristics and glycemic control.@*Results@#80 T2DM patients were included in the analysis, there was an equal number of male (50%) and female (50%). Majority of the patients were in the age of 50 – 59 years old (33%), with a BMI of 25 and above (81%), had been diagnosed with T2DM for > 5 years (72%) and maintained with oral hypoglycemic agents (68%). The prevalence of NAFLD by ultrasonography among T2DM patients was 81%. 80% of these patients had mild NAFLD and 20% had moderate NAFLD; but none had severe NAFLD. The average HbA1c level of 8.9% had a mild NAFLD compared to patients with moderate NAFLD with an average HbA1c level of 10.1%. With a p=0.053, NAFLD severity and glycemic control do not show any statistically significant association. Subgroup analysis was not performed in the study due to limited sample size. In addition, results of association are not sufficient evidence for any conclusion; hence, there appear to be no group of interest.@*Conclusion@#The result of this study confirmed that the prevalence of NAFLD in T2DM was high at 81% but there is no sufficient evidence to conclude a statistically significant association between the level of glycemic control and the severity of NAFLD.

TSPAN8 is involved in lipid metabolism in non-alcoholic fatty liver disease in mice / 南方医科大学学报

OBJECTIVE@#To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.@*RESULTS@#Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001).@*CONCLUSION@#TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.

New advances of artificial intelligence in the diagnosis of non-alcoholic fatty liver disease / 中华肝脏病杂志

Artificial intelligence (AI) refers to the use of computer programs to simulate and extend human intelligence, and has application prospects in the diagnosis and treatment of diseases. This review focuses on the research status of the screening and diagnosis of NAFLD and nonalcoholic steatohepatitis using artificial intelligence technology, electronic health record data, multi-omics prediction models, image recognition technology based on liver imaging and pathological biopsy, and new drugs research and development, with a view to provide new ideas for the diagnosis and treatment.

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.

Exploring the effects of entecavir treatment on the degree of liver fibrosis in patients with non-alcoholic fatty liver combined with chronic hepatitis B in Tibet region / 中华肝脏病杂志

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ2 test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.

Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease / 中华肝脏病杂志

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

Applied research of ultrasound attenuation parameter in the diagnosis of metabolic dysfunction-associated fatty liver disease / 中华肝脏病杂志

Objective: To evaluate the efficacy, establish a diagnostic model, and value of ultrasound attenuation parameters (UAP) to diagnose hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD) and its relevant disorders. Methods: 3770 cases were selected from the Health Examination Center of the Third Hospital of Hebei Medical University between October to December 2020. MAFLD diagnosis was based on the Asia-Pacific region MAFLD clinical diagnosis and treatment guidelines. The degree of hepatic steatosis was divided into mild, moderate and severe according to ultrasound imaging. UAP, clinical characteristic indexes, serum biochemical indexes, characteristics of hepatic steatosis and related factors were compared and analyzed in MAFLD patients and healthy controls. Logistic regression method was used to analyze the independent risk factors affecting the progression of hepatic steatosis in MAFLD to establish the diagnostic model. The clinical efficacy of UAP and the new model in diagnosing MAFLD was evaluated by the receiver operating characteristic curve (ROC). One-way ANOVA was used to compare means among multiple groups. Mann-Whitney U test was used to compare non-normally distributed measurement data between the two groups, and rank-sum test was used to compare multiple groups. χ2 test was used to compare count data between groups. Results: Among the 3 770 cases, 650 were MAFLD, with a prevalence rate of 17.24%, and the highest prevalence was 37.23% in the age group of 60-69. The prevalence rate was significantly higher in male than female (30.34% vs. 9.17%). Age-sex analysis showed that the prevalence rate in males aged 30-69 years was 38.26%, and that in females aged over 60 years was 31.94%. UAP was significantly higher in patients with MAFLD than healthy controls (278.55 dB/m vs. 220.90 dB/m, Z=-12.592, P＜0.001), and an increasing trend with increased degree of hepatic steatosis (mild:257.20 dB/m, moderate:286.20 dB/m, and severe: 315.00 dB/m) were observed. The cut-off values of UAP for the diagnosis of mild, moderate and severe hepatic steatosis were 243≤UAP＜258 dB/m, 258≤UAP＜293 dB/m, ≥293 dB/m in MAFLD. The sensitivity and specificity were 67.20%, 93.60%, 95.90%, and 82.10%, 72.00%, and 84.80%, respectively. UAP, alanine aminotransferase and fasting blood glucose were independent risk factors for the progression of hepatic steatosis in MAFLD. The combined MAFLD classification model (UAG model) was established. The AUC of mild, moderate and severe hepatic steatosis in MAFLD were 0.906, 0.907, and 0.946, respectively, and the sensitivity and specificity were 76.50%, 82.10%, 98.00%, and 90.80%, 83.30% and 76.10%, respectively. Conclusion: MAFLD is a common disease in the general population, with a higher incidence in male and elderly female over 30 years of age. UAP can be used as a new noninvasive diagnostic technique to evaluate hepatic steatosis in MAFLD. The UAG model has a good diagnostic efficacy on MAFLD and its relevant disorders, and thus can be used as a guide for evaluating clinical diagnosis and prognosis.

Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

Mechanism study of the protective effects of selective cyclooxygenase-2 enzyme inhibitors on the liver of rats with type 2 diabetes mellitus combined with nonalcoholic steatohepatitis via Rho/ROCK pathway / 中华肝脏病杂志

Objective: To investigate whether the selective cyclooxygenase-2 enzyme inhibitors celecoxib has protective effect on the liver of rats with type 2 diabetes mellitus (T2DM) combined with nonalcoholic steatohepatitis (NASH) via inhibiting the expression of Rho/ROCK pathway. Methods: Forty male SD rats were randomly divided into four groups: type 2 diabetes mellitus combined with nonalcoholic steatohepatitis (T2DM-NASH) group, T2DM-NASH + celecoxib group, control group, and control+celecoxib group. The T2DM-NASH and T2DM-NASH + celecoxib groups were fed with high-sugar and fat diet, and the control group and control + celecoxib group were fed with basal diet (25 kJ/kg). Four weeks later, streptozotocin (STZ, 30 mg/kg) was intraperitoneally injected into the NASH group and T2DM-NASH + celecoxib group to induce T2DM model, and the control group and control + celecoxib group were intraperitoneally injected with isovolumic citric acid-sodium citrate buffer. Four weeks after STZ injection, the T2DM-NASH + celecoxib group and the control + celecoxib group were gavaged with celecoxib (10 mg·kg·d) dissolved in normal saline for 4 weeks, and the remaining two groups of rats were gavaged with isovolumic normal saline for 4 weeks. Animals were sacrificed at the end of the 12- weeks, and the liver tissue was collected. Liver pathological changes were observed by HE staining. The expressions of RhoA, RhoA, ROCK1 and ROCK2 proteins in liver were detected by immunohistochemistry and western blot. The expressional condition of RhoA, ROCK1 and ROCK2 mRNA in liver were detected by real-time quantitative PCR. The differences were compared between protein and mRNA expression among the groups by analysis of variance and t-test. Results: Compared with the control group and the control + celecoxib group, the liver tissue of the T2DM-NASH group and the T2DM-NASH + celecoxib group had severe steatosis, and there was partial inflammatory cell infiltration under the light microscope. The expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were significantly increased (P < 0.05) in each liver tissue, while liver steatosis was reduced to certain extent in T2DM-NASH + celecoxib group than T2DM-NASH group, and the expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were decreased in each liver tissue of T2DM-NASH group (P < 0.05). Conclusion: The selective cyclooxygenase-2 enzyme inhibitors celecoxib has a protective effect on the liver of rats with T2DM-NASH, and its effect may be achieved by inhibiting the expression of Rho/ROCK pathway.

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.