Linseed oil attenuates fatty liver disease in mice fed a high-carbohydrate diet

The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.2%), and lipids (4.0%). The Control HCD group (HCD-C) received an HCD containing lard (3.6%) and soybean oil (0.4%) as lipid sources. The L10 and L100 groups received an HCD with 10 and 100% linseed oil as lipid sources, respectively. A group of mice were euthanized before receiving the diets (day 0) and the remaining groups after 56 days of receiving the diets (HCD-C, L10, and L-100 groups). Morphological and histopathological analyses, as well as collagen deposition were evaluated. Perivenous hepatocytes (PVH) of the HCD-C group were larger (P<0.05) than periportal hepatocytes (PPH) in the median lobe (ML) and left lobe (LL). There was a greater (P<0.05) deposition of type I collagen in PPH (vs PVH) and in the ML (vs LL). The ML exhibited a higher proportion of apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning. All these alterations (hepatocyte size, deposition of type I collagen, apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning) induced by HCD were prevented or attenuated in L10 and L100 groups. Another indicator of the beneficial effects of linseed oil was the lower (P<0.05) number of binucleated hepatocytes (HCD-C vs L10 or L100 group). In general, the L100 group had greater effects than the L10 group. In conclusion, linseed oil impedes or reduces the liver injury progression induced by an HCD.

Effect of Biling Qutong Prescription on NLRP3， P2X7R， FN， and Hepatic Steatosis in Type 2 Diabetes Mellitus Complicated with Gouty Arthritis / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Biling Qutong prescription （BLQT） on serum levels of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， purinergic ligand-gated ion channel 7 receptor （P2X7R）， fibronectin （FN）， and hepatic steatosis in patients with type 2 diabetes mellitus （T2DM） complicated with gouty arthritis （GA）. MethodSixty-four patients diagnosed with T2DM comorbid with GA and treated at the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to December 2022 were enrolled and randomly divided into a BLQT group （Chinese medicine group， 32 cases） and the ibuprofen group （western medicine group， 32 cases）. Thirty healthy individuals who underwent routine health examinations during the same period were assigned to the control group. The BLQT group and the western medicine group received basic treatment along with BLQT and ibuprofen， respectively. After 8 weeks of continuous treatment， the traditional Chinese medicine syndrome score （TCMSS） of the patients was evaluated before and after treatment. The differences in fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 h PG）， glycated hemoglobin （HbA1c）， fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， serum uric acid （SUA）， serum creatinine （SCr）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， NLRP3， P2X7R， and FN levels before and after treatment were compared. Adverse drug reactions that occurred during treatment were recorded. ResultThe TCMSS for joint redness， swelling， pain， joint burning， yellow urine， and red tongue with yellow and greasy coating， as well as total score were significantly reduced in both the BLQT group and the western medicine group as compared with those before treatment （P<0.05， P<0.01）. The BLQT group also showed a significant reduction in symptom scores such as dry mouth， polyuria， polydipsia， and slippery and rapid pulse （P<0.01）. Compared with the western medicine group after treatment， the BLQT group exhibited a more significant reduction in all symptom scores and total score （P<0.05， P<0.01）. The BLQT group and the western medicine group showed a decrease in FPG， 2 h PG， HbA1c， SCr， SUA， TG， TC， and LDL-C levels （P<0.05， P<0.01） after treatment， and the BLQT group showed decreased HOMA-IR， ALT， AST， and HDL-C levels （P<0.05， P<0.01） compared with those before treatment. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in all laboratory parameters except for HDL-C （P<0.05， P<0.01）. Before treatment， NLRP3， P2X7R， and FN levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， NLRP3 and P2X7R levels in both groups significantly decreased （P<0.01）， and FN levels in the BLQT group also decreased significantly （P<0.01）. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in NLRP3， P2X7R， and FN levels （P<0.01）. Before treatment， CAP and LSM levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， CAP and LSM levels in both groups decreased （P<0.05， P<0.01）. Compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in CAP and LSM （P<0.01）. The incidence of adverse reactions was 3.13% （1/32） in the BLQT group and 15.63% （5/32） in the western medicine group， with no significant difference. ConclusionBLQT has good efficacy in patients with T2DM complicated with GA， which can significantly alleviate joint redness， swelling， heat， pain， limited mobility， dry mouth， and polydipsia， reduce blood glucose， uric acid， and lipid levels， suppress the high expression of NLRP3， P2X7R， and FN， and improve hepatic steatosis.

Correlation analysis of hepatic steatosis, blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B / 公共卫生与预防医学

Objective To analyze the correlation of hepatic steatosis with blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B (CHB). Methods The clinical data of 120 patients with CHB admitted to the hospital from January to December 2021 were retrospectively analyzed. According to the presence or absence of hepatic steatosis, the patients were divided into steatosis group (n=35) and non-steatosis group (n=85). The general clinical data, serological indicators of hepatitis B virus, blood lipid and uric acid levels were compared between the two groups. The correlation of hepatic steatosis grading with blood lipids and uric acid metabolism was analyzed. Results The inflammation and fibrosis degree of liver tissues were significantly different in the two groups (P0.05). Pearson correlation analysis found that the grade of hepatic steatosis in patients with CHB was negatively correlated with liver tissue inflammation, fibrosis degree and HDL-C level (P<0.05), and positively correlated with TG and TC levels (P<0.05). Conclusion Elderly patients with CHB and hepatic steatosis have abnormal blood lipid metabolism. Hepatic steatosis will exacerbate abnormal blood lipid metabolism but not liver tissue inflammation or fibrosis degree. Clinically, attention should be paid to blood lipid monitoring of elderly patients with CHB.

Trajectory of NAFLD characteristics after Roux-en-Y gastric bypass: a five-year historical cohort study

Abstract BACKGROUND: The long-term effects of bariatric surgery on the course of non-alcoholic fatty hepatopathy (NAFLD) are not fully understood. OBJECTIVE: To analyze the evolution of NAFLD characteristics through noninvasive markers after Roux-en-Y gastric bypass (RYGB) over a five-year period. DESIGN AND SETTING: Historical cohort study; tertiary-level university hospital. METHODS: The evolution of NAFLD-related characteristics was evaluated among 49 individuals who underwent RYGB, with a five-year follow-up. Steatosis was evaluated through the hepatic steatosis index (HSI), steatohepatitis through the clinical score for non-alcoholic steatohepatitis (C-NASH) and fibrosis through the NAFLD fibrosis score (NFS). RESULTS: 91.8% of the individuals were female. The mean age was 38.3 ± 10 years and average body mass index (BMI), 37.4 ± 2.3 kg/m2. HSI significantly decreased from 47.15 ± 4.27 to 36.03 ± 3.72 at 12 months (P < 0.01), without other significant changes up to 60 months. C-NASH significantly decreased from 0.75 ± 1.25 to 0.29 ± 0.7 at 12 months (P < 0.01), without other significant changes up to 60 months. NFS decreased from 1.14 ± 1.23 to 0.27 ± 0.99 at 12 months (P < 0.01), and then followed a slightly ascending course, with a marked increase by 60 months (0.82 ± 0.89), but still lower than at baseline (P < 0.05). HSI variation strongly correlated with the five-year percentage total weight loss (R = 0.8; P < 0.0001). CONCLUSION: RYGB led to significant improvement of steatosis, steatohepatitis and fibrosis after five years. Fibrosis was the most refractory abnormality, with a slightly ascending trend after two years. Steatosis improvement directly correlated with weight loss.

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

Effect of hepatic fibrosis on proton density fat fraction based on histogram analysis in evaluating hepatic steatosis: an experimental study / 中华放射学杂志

Objective:To explore the value of proton density fat fraction(PDFF) based on histogram analysis for quantification hepatic steatosis and fibrosis in rabbit model and the interference of hepatic fibrosis to the evaluation of hepatic steatosis with PDFF.Methods:From March to November 2020, 135 New Zealand white rabbits were randomly divided into control group ( n=30) and experimental group ( n=105) using a random number table. The volume ratio of CCl 4 and olive oil was 1∶1 to prepare 50% CCl 4 oil solution, and experimental rabbits were subcutaneously injected with the oil solution. An equal dose of normal saline was subcutaneously injected for control group rabbits. At the end of the 4 th, 8 th, and 12 th week, 35 in the experimental group and 10 rabbits in the control group were randomly selected to conduct the mDixon-Quant scanning, and histogram analysis of PDFF was analyzed including volume, mean, median, standard deviation, 25 th, 50 th, 75 th, 90 th quantile, skewness, kurtosis, entropy and inhomogeneity. After the examination, the rabbits were sacrificed and the liver percentage of steatosis (PSH) and fibrosis (POF) were recorded by semi-quantitative analysis. Spearman correlation analysis was used to correlate PDFF with PSH and POF. Multiple linear regression analysis was used to determine independent PDFF histogram parameters for evaluating PSH and POF. A receiver operator characteristic (ROC) curve was used to assess the diagnostic accuracy of PDFF for discriminating mild from moderate-severe hepatic steatosis and mild from moderate-severe hepatic fibrosis with median of PSH or POF for dichotomy, and DeLong test was used to compare the area under the curve (AUC). With the correction of hepatic fibrosis, correlation coefficient and AUC were compared of PDFF for discrimination mild from moderate-severe hepatic steatosis. Results:The PDFF mean, median, standard deviation, 75 th, 90 th showed correlation with PSH ( r=0.558, 0.522, 0.319, 0.723, 0.646, -0.589, all P<0.05). The entropy and 75 th were independent parameters for evaluating PSH (β=2.347, -5.960, P=0.018, 0.001). The PDFF 75 th was the optimal parameter for discriminating mild from moderate-severe hepatic steatosis with AUC=0.915 ( P=0.001). The PDFF volume, mean, median, standard deviation, 75 th, 90 th, entropy showed correlation with POF ( r=0.355, 0.393, 0.376, 0.298, 0.485, 0.426, -0.681, all P<0.05). The entropy, standard deviation and volume (β=-11.041, 1.356, 0.190, P=0.001, 0.026, 0.016) were independent parameters for evaluation of hepatic fibrosis, and the entropy was the optimal parameter for hepatic fibrosis (AUC=0.771, P=0.001). The correlation between PSH and PDFF 75 th was less pronounced when fibrosis was present ( r=0.512, P=0.001) than when fibrosis was absent ( r=0.751, P=0.002). The PDFF 75 th showed a significant difference in discriminating mild hepatic steatosis from moderate-severe hepatic steatosis after correction of POF (AUC=0.895, 0.950, Z=2.970, P=0.025). Conclusions:PDFF based on histogram analysis provided a noninvasive, accurate estimation of quantification for hepatic steatosis and fibrosis. Hepatic fibrosis reduced the correlation between hepatic steatosis and PDFF and the presence of hepatic fibrosis can confound the quantification of hepatic steatosis with PDFF.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Assessment of chronic kidney disease in patients with non-alcoholic fatty liver disease (NAFLD); A single center experience

Background: Non-alcoholic fatty liver disease (NAFLD) represents a considerable percentage of chronic liver diseases worldwide. The liver is not the only organ affected by NAFLD but also affects other organs such as the cardiovascular system and the kidney. In recent decades, there has been a growing body of evidence linking NAFLD to kidney function. So, the current study aims to assess the percentage of chronic kidney disease (CKD) in NAFLD patients and its link to different stages of hepatic fibrosis. Patients and Methods: A case-control study evaluated 62 non-alcoholic fatty liver disease patients and a control group of 38 volunteers with apparently healthy livers (normal echo pattern by ultrasound). All participants underwent serum creatinine measurement, albumin creatinine ratio in urine, calculation of estimated glomerular filtration rate (eGFR), abdominal ultrasound, and fibroScan examination. Results: The authors showed that the percentage of patients with chronic kidney diseases (patients with GFR less than 60 ml or micro-albuminuria) were significantly higher among NAFLD groups than in healthy controls. There was a significant positive correlation between the albumin creatinine ratio and subcutaneous fat thickness, BMI, and steatosis degrees. The estimated glomerular filtration rate (eGFR) and the age of the patients had a significant negative correlation. In comparison, the eGFR and AST levels had a significant positive correlation. Conclusions: Our results showed that NAFLD substantially raises the risk of getting CKD

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe -/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Relação monócito/HDL em esteatose não hepática / Monocyte/hdl ratio in non-alcoholic hepatic steatosis

ABSTRACT BACKGROUND: Non-alcoholic hepatic steatosis (NAS) is characterized by excess fat accumulation in hepatocytes, causing portal and lobular inflammation and hepatocyte injury. OBJECTIVE: We aimed to evaluate the alterations in monocyte count to high-density lipoprotein cholesterol ratio (MHR) in patients with grade 2 or 3 fatty liver disease and the association of this marker with liver function tests and insulin resistance. METHODS: In this retrospective analysis; patients diagnosed and followed for the grade 2 or 3 fatty liver disease were included in the patient group and the patients who had undergone abdominal ultrasound for any reason and who were not having any fatty liver disease were included in the control group. RESULTS: Totally 409 cases were included in the study. Among participants, 201 were in the control group, and 208 were in the NAS group (111 were having grade 2 and 97 were having grade 3 steatosis). The monocyte/HDL ratio was significantly higher in the NAS group compared with the healthy controls (P=0.001). There was a significant positive correlation between the monocyte/HDL ratio and age (r=0.109; P=0.028), ALT (r=0.123, P=0.014) and HOMA-IR (r=0.325, P=0.001) values. CONCLUSION: In conclusion, the monocyte to high-density lipoprotein ratio significantly increases in fatty liver disease and correlates with insulin resistance. Since it was suggested as a prognostic marker in atherosclerotic diseases, elevated MHR values in fatty liver disease should be evaluated cautiously.

RESUMO CONTEXTO: A esteatose não hepática (ENH) é caracterizada pelo acúmulo de gordura nos hepatócitos, causando inflamação portal e lobular e lesões ao hepatócito. OBJETIVO: Avaliar as alterações na contagem de monócitos em relação à proporção de lipoproteína de colesterol de alta densidade (MHR) em doentes com doença hepática gordurosa de grau 2 ou 3 e a associação deste marcador com testes de função hepática e de resistência à insulina. MÉTODOS: Nesta análise retrospectiva os pacientes diagnosticados e seguidos para a doença hepática gordurosa de grau 2 ou 3, foram incluídos no grupo de doentes e os indivíduos que tinham sido submetidos a ecografia abdominal por qualquer motivo e que não tinham qualquer doença hepática gordurosa foram incluídos no de controle. RESULTADOS: Foram incluídos 409 pacientes no estudo. Entre os participantes, 201 estavam no grupo controle e 208 estavam no grupo ENH (111 caracterizados como grau 2 e 97 com esteatose de grau 3). A relação monócito/HDL foi significativamente maior no grupo ENH em comparação com os controles saudáveis (P=0,001). Verificou-se correlação positiva significativa entre a relação monócitos/HDL e a idade (r=0,109; P=0,028), e valores de ALT (r=0,123; P=0,014) e HOMA-IR (r=0,325; P=0,001). CONCLUSÃO: A razão entre monócitos e a lipoproteína de alta densidade aumenta significativamente na doença hepática gordurosa e correlaciona-se com a resistência à insulina. Uma vez que foi sugerido como um marcador prognóstico em doenças ateroscleróticas, os valores elevados de MHR na doença hepática gordurosa devem ser avaliados com cautela.

Correlation between COVID-19 severity, body mass index and radiological hepatic morphology / Correlación entre la gravedad de COVID-19, el índice de masa corporal y la morfología hepática radiológica

SUMMARY: Obesity and fatty liver steatosis are already considered metabolic risk factors which may aggravate the severity of COVID-19. This study aims to investigate the correlation between COVID-19 severity, obesity, and liver steatosis and fibrosis. 230 consecutive patients with laboratory-confirmed COVID-19 aged between 15 and 84? years, admitted to a hospital devoted to COVID-19 patients, were enrolled in the study. COVID-19 severity was classified as severe versus non-severe based on admission to ICU. Obesity was assessed by Body Mass Index (BMI). CT-scan was used to check for the liver steatosis. Fibrosis-4 score was calculated. The study was conducted in March-May 2020. Obesity strongly and positively correlated with severe COVID-19 illness r: 0.760 (P<0.001). Hepatic steatosis had rather less of a correlation with COVID-19 severity r: 0.365 (P<0.001). Multivariable-adjusted association between hepatic steatosis or obesity, or both (as exposure) and COVID-19 severity (as the outcome) revealed increased risk of severe COVID-19 illness with obesity (Adjusted model I OR: 465.3, 95 % CI: 21.9-9873.3, P<0.001), with hepatic steatosis (Adjusted model I OR: 5.1, 95 % CI: 1.2-21.0, P<0.025), and with hepatic steatosis among obese patients (Adjusted model I OR: 132, 95 % CI: 10.3-1691.8, P<0.001). Obesity remained the most noticeable factor that strongly correlated with COVID-19 severity, more than liver steatosis. However, the risk to COVID-19 severity was greater in those with both factors: obesity and liver steatosis.

RESUMEN: La obesidad y la esteatosis del hígado graso ya se consideran factores de riesgo metabólico que pueden empeorar la gravedad de la COVID-19. Este estudio tiene como objetivo investigar la correlación entre la gravedad de COVID- 19, la obesidad y la esteatosis y fibrosis hepática. El estudio se realizó en 230 pacientes consecutivos entre 15 y 84 años con COVID-19 confirmado por laboratorio, ingresados en un hospital dedicado a pacientes con COVID-19. La gravedad de COVID-19 se clasificó como grave, versus no grave según el ingreso a la UCI. La obesidad se evaluó mediante el índice de masa corporal (IMC). Se utilizó una tomografía computarizada para verificar la esteatosis hepática. Se calculó la puntuación de Fibrosis-4. El estudio se realizó entre marzo-mayo de 2020. La obesidad se correlacionó fuerte y positivamente con la enfermedad grave de COVID-19 r: 0,760 (P <0,001). La esteatosis hepática tuvo una correlación bastante menor con la gravedad de COVID-19 r: 0.365 (P <0.001). La asociación ajustada multivariable entre la esteatosis hepática u obesidad, o ambas (como exposición) y la gravedad de COVID-19 (como resul- tado) reveló un mayor riesgo de enfermedad grave por COVID- 19 con obesidad (OR del modelo ajustado I: 465,3, IC del 95%: 21,9 -9873,3, P <0,001), con esteatosis hepática (OR del modelo I ajustado: 5,1, IC del 95 %: 1,2-21,0, P <0,025) y con esteatosis hepática entre los pacientes obesos (OR del modelo I ajustado: 132, IC del 95 % : 10,3-1691,8, P <0,001). La obesidad siguió siendo el factor más notable que se correlacionó significativamente con la gravedad de COVID-19, más que la esteatosis hepática. Sin embargo, el riesgo de gravedad de COVID-19 fue mayor en aquellos con ambos factores: la obesidad y esteatosis hepática.

Homeostase glicêmica e marcadores antropométricos associados à resistência insulínica em pacientes portadores de doença hepática gordurosa não alcoólica / Glycemic homeostasis and anthropometric markers associated with insulin resistance in patients with non-alcoholic fatty liver disease

Objetivo: Determinar medidas antropométricas preditivas associadas à resistência à insulina em pacientes portadores de doença hepática gordurosa não alcoólica. Métodos: Estudo transversal, quantitativo, realizado em dois centros ambulatoriais de Recife-PE. O público foi formado por indivíduos de ambos os sexos, acima de 18 anos, com diagnóstico de doença hepática gordurosa não alcoólica via ecografia abdominal. As variáveis antropométricas coletadas foram: circunferência da cintura, índice de massa corporal, índice de conicidade, razão cintura-quadril e cintura-estatura. A resistência à insulina foi determinada através do Homeostasis model assessment: insulin resistance (HOMA-IR). Para entender as diferenças entre as variáveis, o teste de U Mann-Whitney e testes de correlação foram realizados. Resultados: Participaram 75 indivíduos com predominância do sexo feminino (85%) e com idade superior a 60 anos (44%). A resistência à insulina foi elevada na população, perfazendo mais da metade dos indivíduos (73%). Com exceção do índice de massa corporal e da razão cintura-quadril, demais índices apresentaram associação estatisticamente significativa entre a presença da resistência à insulina com a esteatose hepática não alcoólica: razão cintura-estatura (p=0,004), índice de conicidade (p=0,031) e circunferência da cintura (p=0,001). No teste de correlação, apenas a circunferência da cintura (r =0,2184; p=0,05) e a razão cintura-quadril (r =0,2310; p=0,04) associaram-se. Conclusões: Os indicadores antropométricos são ferramentas aplicáveis na prática clínica e no contexto de doença hepática gordurosa não alcoólica; contudo, a circunferência da cintura e as razões cintura-estatura e cintura-quadril apresentaram as melhores predições. (AU)

Objective: To determine predictive anthropometric measurements associated with insulin resistance in patients with non-alcoholic fatty liver disease. Methods: This was a cross-sectional, quantitative study conducted at two outpatient clinics in Recife-PE. The study group was formed by individuals of both sexes over 18 years of age with non-alcoholic fatty liver disease diagnosed via abdominal echography. The anthropometric variables collected were: waist circumference, body mass index, conicity index, waist-to-hip ratio, and waist-to-height ratio. Insulin resistance was determined through the homeostasis model assessment: insulin resistance (HOMA-IR). The Mann­Whitney U test and correlation tests were performed to understand the differences between the variables. Results: 75 individuals participated in the study, most of whom were female (85%) and with age over 60 years (44%). Insulin resistance was high in the population, being present in more than half of the individuals (73%). Except for the body mass index and waist-to-hip ratio, all other indices showed a significant association between the presence of insulin resistance and non-alcoholic hepatic steatosis: waist-to-height ratio (p= 0.004), conicity index (p= 0.031), and waist circumference (p= 0.001). In the correlation test, only the waist circumference (r= 0.2184; p= 0.05) and the waist-to-hip ratio (r = 0.2310; p= 0.04) were associated. Conclusions: The anthropometric indicators are applicable tools in clinical practice and in the context of non-alcoholic fatty liver disease; however, waist circumference and the waist-to-height and waist-to-hip ratios provided the best predictions. (AU)

Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis,

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.

Estructura y función ventriculares en la enfermedad de hígado graso no alcohólica / Ventricular structure and function in non-alcoholic fatty liver disease

RESUMEN La enfermedad del hígado graso no alcohólica se asocia al síndrome metabólico y a la enfermedad cardiovascular a través de múltiples vías patogénicas, que incluyen la resistencia a la insulina, la alteración del metabolismo lipídico, inflamación y disfunción endotelial. Estos mecanismos conducen a remodelación cardíaca, aterosclerosis y un aumento potencial de la morbilidad y la mortalidad cardiovasculares. En esta breve revisión se abordan las relaciones de la enfermedad del hígado graso no alcohólica con el síndrome metabólico y su impacto en las pruebas de imagen y en los marcadores bioquímicos de función ventricular.

ABSTRACT Nonalcoholic fatty liver disease is associated with metabolic syndrome and cardiovascular disease through multiple pathogenic pathways including insulin resistance, altered lipid metabolism, inflammation and endothelial dysfunction. These mechanisms lead to cardiac remodeling, atherosclerosis, and potentially increased cardiovascular morbidity and mortality. In this short review we address the relationships of non-alcoholic fatty liver disease with metabolic syndrome and their impact on imaging and biochemical markers of ventricular function.

Doença Hepática Gordurosa Não Alcoólica em crianças e adolescentes / Non-alcoholic fatty liver disease in childhood and adolescence

A obesidade infantil é uma epidemia mundial. São várias as comorbidades associadas à obesidade, destacando-se a doença hepática gordurosa não alcoólica (DHGNA), um termo abrangente que envolve desde a esteatose hepatocelular simples até quadros mais avançados de esteato-hepatite, fibrose e cirrose hepática. Atualmente, é a segunda maior causa de transplante hepático em adultos nos Estados Unidos, com potencial de se tornar a primeira nas próximas décadas. Associado a este panorama, ainda existe o desafio do diagnóstico, uma vez que os critérios clínicos e laboratoriais ainda são controversos, especialmente em crianças. A biópsia é o padrão ouro, entretanto é um procedimento invasivo e sujeito a riscos. Por isso, a dosagem de enzimas hepáticas e a ultrassonografia abdominal são utilizadas para triagem e avaliação, apesar de suas limitações. O tratamento de DHGNA deve obrigatoriamente incluir a abordagem da obesidade. Por isso, os pilares do tratamento envolvem a mudança do estilo de vida e dos hábitos alimentares. Embora a eficácia de várias medicações venha sendo estudada, a alimentação saudável e a atividade física permanecem como a mais importante estratégia de prevenção e tratamento da DHGNA na infância e adolescência. A equipe multidisciplinar deve, junto ao paciente e a família, construir uma rotina de hábitos alimentares e atividades físicas adequadas para cada caso. (AU)

Childhood obesity is a worldwide epidemic. There are several comorbidities associated with obesity, including non-alcoholic fatty liver disease (NAFLD), a wide term that ranges from a hepatocellular steatosis to more advanced steatohepatitis, fibrosis and liver cirrhosis. This is the second major cause of liver transplant in adults in the United States, with the potential to become the first one in the next few decades. Associated with this scenario, the challenge of diagnosis still exists, since screening is still controversial, especially in children. Biopsy is the gold standard, but it is an invasive and risky procedure. Therefore liver enzymes and abdominal ultrasound are used for screening and assessment although their limitations. Treatment of NAFLD should involve an approach to obesity with focus in lifestyle intervention and healthy diet. While the efficacy of several medications has been investigated in children, healthy diet and physical activity remain the only prevention and treatment strategies for paediatric NAFLD. A multidisciplinary team should, together with the patient and a family, build a routine of healthy eating and physical activities (AU)

Effect of ophiopogonin D on serum lipids and intestinal flora in ApoE-/- mice with high-fat diet / 中草药

Objective: To investigate the effect of ophiopogonin D (OP-D) on blood lipids and intestinal flora in ApoE-/- mice fed with high-fat diet (HFD). Methods: A total of 24 male ApoE-/- mice, aged six weeks old, were randomly divided into control group, model group, OP-D group [0.5 mg/(kg∙d)] and simvastatin group [5 mg/(kg∙d)]. Another six male C57BL/6 mice were in blank group. After 12 weeks of HFD, the drugs were given by intragastric administration for 12 weeks. After the end of administration, fresh feces of mice were collected to detect intestinal flora. Serum of mice was separated to detect blood lipid. Liver section staining was prepared to observe the damage. Results: OP-D could reduce the weight gain of mice caused by HFD, inhibit the increase of total cholesterol and triglyceride, improve hepatic steatosis, and regulate intestinal flora imbalance. Conclusion: OP-D may regulate blood lipids and hepatic steatosis by improving intestinal flora imbalance induced by HFD in ApoE-/- mice.

NF- B/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis

The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of knockout (-KO) mice and knockout (-KO) mice. Hepatic steatosis was reduced in the -KO mice, but not in the -KO mice. The reduction was a result of inhibition of HDAC1 activity in the -KO cells. Knockdown of gene led to suppression of hepatocyte steatosis in HepG2 cells. A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of -KO mice and in cell with knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the -KO, but not the -KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.

Utilidad de la ecografía en el diagnóstico de esteatosis hepática en niños con sobrepeso u obesidad que concurren al Hospital Regional de Encarnación de marzo a junio de 2019

RESUMEN La obesidad infantil va en aumento, relacionado a los malos hábitos alimentarios y el sedentarismo; puede desembocar en el desarrollo del síndrome metabólico, incrementando el riesgo de enfermedades crónicas, entre ellas, la esteatosis hepática. El objetivo de este estudio fue determinar la utilidad de la ecografía en la detección de esteatosis hepática en niños con sobrepeso u obesidad que concurrieron al Hospital Regional de Encarnación de marzo a junio de 2019. Se estudiaron a 50 niños de ambos sexos de 5 a 14 años con sobrepeso u obesidad, mediante examen clínico, antropometría, ecografía y marcadores bioquímicos. Se encontraron 18 pacientes (36%) con esteatosis hepática, mediante ecografía, predominando en varones, con obesidad severa de tipo visceral. La Acantosis nigricans, el perímetro abdominal por encima del percentil 90, GPT y triglicéridos séricos elevados, fueron los hallazgos más relevantes asociados a esteatosis hepática. La ecografía simple en modo B, resultó ser un método útil para la detección de esteatosis hepática en niños obesos, asociado a la presencia de perímetro abdominal por encima del percentil 90, Acantosis Nigricans, GPT y triglicéridos elevados. Este esquema de manejo inicial sería muy útil y de fácil aplicación en la evaluación y control de esta afección que va en aumento en la población pediátrica.

ABSTRACT Childhood obesity is increasing, related to bad eating habits and sedentary lifestyle; It can lead to the development of metabolic syndrome, increasing the risk of chronic diseases, including liver steatosis. The objective of this study was to determine the usefulness of ultrasound in the detection of hepatic steatosis in overweight or obese children who attended the Regional Hospital of Encarnación from March to June 2019. Fifty children of both sexes from 5 to 14 years old were studied with overweight or obesity, through clinical examination, anthropometry, ultrasound and biochemical markers. 18 patients (36%) were found with hepatic steatosis, by ultrasound, predominantly in men, with severe obesity of visceral type. Acanthosis nigricans, the abdominal perimeter above the 90th percentile, GPT and elevated serum triglycerides, were the most relevant findings associated with hepatic steatosis. Simple B-mode ultrasound proved to be a useful method for the detection of hepatic steatosis in obese children, associated with the presence of abdominal perimeter above the 90th percentile, Acanthosis nigricans, GPT and elevated triglycerides. This initial management scheme would be very useful and easy to apply in the evaluation and control of this condition that is increasing in the pediatric population.

Etiology and Impact of Hepatic Steatosis in Pakistan: Role of Hepatitis C Virus Genotype 3 Infection

Introduction: Hepatic steatosis has emerged as an important histological finding in patients with deranged liver function. It may be an important factor for the progression of hepatitis C virus-associated liver disease, particularly in genotype 3 infections. Aims: To determine the etiology and impact of hepatic steatosis in our patients presenting with chronic hepatitis. Methods: All liver biopsies performed at our hospital during 2010-2014 were analyzed by a single pathologist using histological activity index (HAI) scores and Brunt’s classification for steatosis. Patients were evaluated for factors reported to be associated with steatosis, including the prevalence of HCV. Results: Biopsies of 439 patients (284 male, mean ages 38.5 ± 11.2 years) were studied. Hepatic steatosis was present in 324 (73.8%) biopsies. It was mild in 190/439 (43.3%), moderate in 88/439 (20%) and severe in 46/439 (10.5%) cases. On univariate analysis, steatosis was associated with HCV infection (p=0.023), BMI >25 (p=0.008) and raised ALT (p=0.003), but not with diabetes, hypertriglyceridemia, HBV infection or alcohol intake. On multiple logistic regression HCV and BMI >25 were independent risk factors for steatosis. There was a linear ascending association of hepatic steatosis with grade and stage of liver disease (p ≤ 0.001). Among 369 HCV patients, 280 (76%) had steatosis. It was mild in 159/369 (43%), moderate in 82/369 (22.2%) and severe in 39/369 (10.6%) cases. There were only 32 non-alcoholic, non-viral hepatitis patients and 8/32 (25%) had moderate or severe steatosis. Conclusions: Significant hepatic steatosis is present in 30.5% of our patients with chronic hepatitis. HCV genotype 3 infection is the predominant factor for hepatic steatosis in Pakistan. Steatosis has a linear ascending correlation with hepatic inflammation and fibrosis.