Estudio de la citoqueratina- 18 como marcador no invasivo en pacientes con enfermedad de hígado graso no alcohólico

Introducción: La enfermedad por hígado graso no alcohólico es una de las principales causas de afección hepática. La citoqueratina 18 surge como marcador no invasivo para la valoración de fibrosis hepática. El objetivo del trabajo fue validar el uso de la citoqueratina 18 en sangre periférica en el diagnóstico y evolución de los pacientes con enfermedad por hígado graso no alcohólico. Metodología: Para validar la citoqueratina 18 en el diagnóstico se realizó un estudio de tipo caso-control. El grupo caso fueron los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de enfermedad por hígado graso no alcohólico vinculado al síndrome metabólico, captados entre 2/2/2019 al 2/2/2020. El grupo control fueron personas donantes de sangre. Se parearon 1-1 por edad y sexo. Se cuantificó la citoqueratina 18 en sangre periférica de ambos grupos. Para validar la citoqueratina 18 en la evolución de los pacientes con enfermedad de hígado graso no alcohólico se realizó un trabajo prospectivo, longitudinal. El grupo de pacientes captados fueron seguidos durante un año bajo tratamiento estándar, finalizando el mismo se realizó la cuantificación de citoqueratina 18 en sangre periférica. Las variables continuas se expresan con la media y desvío estándar. Se analizó con test de t Student, error α < 5% Resultados: 13 pacientes integran el grupo caso (12 mujeres), de 53 ± 11 años, con IMC 35.01 ± 8.9 kg/m2. El valor de citoqueratina 18 pre-tratamiento fue de 1410 ± 120 UI, y el valor post-tratamiento fue de 117 ± 56, p < 0,005.El grupo control fueron 13 personas (12 mujeres), de 43,4 ± 8,1 años e IMC 28,10 ± 5,4 kg/m2 El valor de citoqueratina 18 fue de 193 ± 7.2 UI, p < 0.005 vs grupo caso pretratamiento. Conclusiones: La citoqueratina 18 es más elevada en los pacientes con enfermedad hígado graso no alcohólico, siendo estadísticamente significativa y disminuye con el tratamiento con significación estadística, pudiendo constituirse en un marcador útil en este grupo de pacientes.

Introduction: Nonalcoholic fatty liver disease is one of the main causes of liver disease. Cytokeratin 18 emerges as a non-invasive marker for the assessment of liver fibrosis. The objective of the work was to validate the use of cytokeratin 18 in peripheral blood in the diagnosis and evolution of patients with non-alcoholic fatty liver disease. Methodology: To validate cytokeratin 18 in the diagnosis, a case-control study was carried out. The case group was patients over 18 years of age, of both sexes, with a diagnosis of non-alcoholic fatty liver disease linked to metabolic syndrome, recruited between 2/2/2019 to 2/2/2020. The control group were blood donors. They were matched 1-1 for age and sex. Cytokeratin 18 was quantified in peripheral blood of both groups. To validate cytokeratin 18 in the evolution of patients with non-alcoholic fatty liver disease, a prospective, longitudinal study was carried out. The group of patients recruited were followed for one year under standard treatment, at the end of which cytokeratin 18 was quantified in peripheral blood. Continuous variables are expressed with the mean and standard deviation. It was analyzed with Student's t test, α error < 5%. Results: 13 patients make up the case group (12 women), 53 ± 11 years old, with BMI 35.01 ± 8.9 kg/m2. The pre-treatment cytokeratin 18 value was 1410 ± 120 IU, and the post-treatment value was 117 ± 56, p < 0.005. The control group was 13 people (12 women), 43.4 ± 8.1 years and BMI 28.10 ± 5.4 kg/m2 The cytokeratin 18 value was 193 ± 7.2 IU, p < 0.005 vs. pretreatment case group. Conclusions: Cytokeratin 18 is higher in patients with non-alcoholic fatty liver disease, being statistically significant, and decreases with treatment with statistical significance, and may become a useful marker in this group of patients.

Introdução: A doença hepática gordurosa não alcoólica é uma das principais causas de doença hepática. A citoqueratina 18 surge como um marcador não invasivo para avaliação de fibrose hepática. O objetivo do trabalho foi validar o uso da citoqueratina 18 no sangue periférico no diagnóstico e evolução de pacientes com doença hepática gordurosa não alcoólica. Metodologia: Para validar a citoqueratina 18 no diagnóstico, foi realizado um estudo caso-controle. O grupo caso foi composto por pacientes maiores de 18 anos, de ambos os sexos, com diagnóstico de doença hepática gordurosa não alcoólica ligada à síndrome metabólica, recrutados entre 02/02/2019 a 02/02/2020. O grupo controle eram doadores de sangue. Eles foram comparados em 1 a 1 por idade e sexo. A citoqueratina 18 foi quantificada no sangue periférico de ambos os grupos. Para validar a citoqueratina 18 na evolução de pacientes com doença hepática gordurosa não alcoólica, foi realizado um estudo prospectivo e longitudinal. O grupo de pacientes recrutados foi acompanhado durante um ano sob tratamento padrão, ao final do qual a citoqueratina 18 foi quantificada no sangue periférico. As variáveis ​​contínuas são expressas com média e desvio padrão. Foi analisado com teste t de Student, erro α < 5%. Resultados: Compõem o grupo caso 13 pacientes (12 mulheres), 53 ± 11 anos, com IMC 35,01 ± 8,9 kg/m2. O valor de citoqueratina 18 pré-tratamento foi de 1410 ± 120 UI e o valor pós-tratamento foi de 117 ± 56, p < 0,005. O grupo controle foi de 13 pessoas (12 mulheres), 43,4 ± 8,1 anos e IMC 28,10 ± 5,4 kg/m2 O valor da citoqueratina 18 foi de 193 ± 7,2 UI, p < 0,005 vs. grupo de casos pré-tratamento. Conclusões: A citoqueratina 18 é maior em pacientes com doença hepática gordurosa não alcoólica, sendo estatisticamente significativa, e diminui com o tratamento com significância estatística, podendo se tornar um marcador útil neste grupo de pacientes.

Gastrodin Inhibits Non-alcoholic Fatty Liver Disease via Mediating SREBP1c Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c （SREBP1c） signaling pathway in high-fat high-cholesterol diet （HFHC）-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease （NAFLD）. MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups， with six mice in each group： normal group， gastrodin group （50 mg·kg-1）， model group， and model + gastrodin group （50 mg·kg-1）. NAFLD model was established by feeding mice with HFHC for four weeks， and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups， and induced with free fatty acids （FFA， 200 μmol·L-1， oleic acid-palmitic acid 2∶1） to establish an NAFLD cell model. After 24 h， different concentrations of gastrodin （0， 5， 10， 20， and 40 μmol·L-1） were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin （HE） staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and triglycerides （TG） were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC， TG， and FFA levels. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）， and stearoyl-CoA desaturase 1 （SCD1）. ResultCompared with the normal group， the model group showed significantly increased serum TC， LDL-C， and TG levels （P<0.01）， liver TC， TG， and FFA levels （P<0.01）， increased lipid accumulation in Huh7 cells （P<0.01）， and significantly increased expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells （P<0.01）. Compared with the model group， after gastrodin treatment， the serum TC， LDL-C， and TG levels in mice significantly decreased （P<0.05， P<0.01）， the severity of fatty liver disease improved significantly， liver TC， TG， and FFA levels decreased significantly （P<0.05， P<0.01）， lipid accumulation in Huh7 cells decreased significantly （P<0.05， P<0.01）， the expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells decreased significantly （P<0.05， P<0.01）. ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels， improve HFHC-induced NAFLD， and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.

Research Progress of miRNA in Non-alcoholic Fatty Liver Disease / 昆明医科大学学报

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,with a global prevalence of approximately 30.05% to 32.4% .It is closely associated with various other diseases.In recent years,microRNAs(miRNAs)have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD.miRNAs play significant roles in both lipid metabolism and insulin resistance,exerting specific regulatory functions in the development and progression of NAFLD.miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes.This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism,insulin resistance,and the occurrence and development of NAFLD.

Advances in epigenetics of nonalcoholic fatty liver desease / 复旦学报（医学版）

Nonalcoholic fatty liver disease(NAFLD)is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis(NASH).NASH is characterized by persistent liver damage,inflammation,and fibrosis which significantly increases the risk of end-stage liver diseases,such as liver cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD/NASH is not yet fully understood,but its recent epigenetic advances have provided new insights into the mechanisms of this disease.This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection,diagnosis,and treatment of this disease.

Testosterone and non-alcoholic fatty liver disease in men and women: A Mendelian randomization study / 中华内分泌代谢杂志

Objective:To investigate the causal association between testosterone and nonalcoholic fatty liver disease(NAFLD) in men and women using a two-sample Mendelian randomization(MR) approach.Methods:Genetic variation in testosterone(total testosterone, bioavailable testosterone) and sex hormone-binding globulin(SHBG) in females and males was used as an instrumental variable using the genome-wide association study(GWAS) pooled data, and the inverse variance weighting method was applied. Inverse variance weighted(IVW) was used as the main analytical method, along with six univariate MR methods based on other modeling assumptions to assess the causal relationship between testosterone(total testosterone, bioavailable testosterone) as well as SHBG and NAFLD in women and men. In addition, NAFLD data from Finnish Biobank(FinnGen) were applied to validate the results of the exploratory analysis. Further, sensitivity analyses were performed to assess the level of heterogeneity, genetic pleiotropy, and stability of the instrumental variables using Cochran′ s Q test, MR-Egger regression, and leave-one-out methods. Results:The results of exploratory analysis of IVW model showed that bioavailable testosterone and SHBG were causally associated with NAFLD in women, for each unit increase in bioavailable testosterone levels, the risk of developing non-alcoholic fatty liver disease(NAFLD) rose by 24%( OR=1.24, 95% CI 1.07-1.43, P=0.004); and with each unit decrease in women′s SHBG, the NAFLD risk increased by 31%( OR=0.69, 95% CI 0.57-0.83, P<0.001). However, testosterone(total testosterone, bioavailable testosterone) as well as SHBG in men and female total testosterone did not show a causal relationship with NAFLD. The results of the other six MR methods were generally consistent with the IVW method. The results of the external validation data provided further evidence of a causal relationship between female bioavailable testosterone and SHBG and NAFLD. Conclusion:Elevated levels of bioavailable testosterone along lower levels of SHBG may increase the risk of developing NAFLD in women.

Efficacy and safety of probiotics in the treatment of nonalcoholic fatty liver disease：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of probiotics in the treatment of nonalcoholic fatty liver disease （NAFLD）. METHODS Retrieved from CNKI， Wanfang data， VIP， SinoMed， PubMed， Embase， Web of Science， Cochrane library databases， the published randomized controlled trials （RCTs） about probiotics（treatment group） versus placebo or healthy lifestyle（control group） in the treatment of NAFLD were collected from the inception to Oct. 10th， 2023. The quality of the included literature was evaluated and rated by Cochrane system evaluator manual 5.1.0 and GRADE tools. Meta-analysis and Egger’s test were carried out by using RevMan 5.4 and Stata 17.0 software. RESULTS Overall 24 RCTs were included in this study， involving 1 391 patients with NAFLD. Meta-analysis showed that compared with control group， the levels of alanine aminotransferase [MD＝－6.29， 95%CI （－9.35， －3.22）， P＜0.000 1]， aspartate aminotransferase [MD＝－4.89， 95%CI （－7.55， －2.23）， P＝0.000 3] and γ-glutamyl transferase [MD＝－4.87， 95%CI （－6.54， －3.20）， P＜0.000 01]， the liver stiffness measurement [MD＝－0.36， 95%CI （－0.48， －0.24）， P＜0.000 01]， the levels of triglycerides [MD＝－0.22， 95%CI （－0.27， －0.16）， P＜0.000 01]， total cholesterol [MD＝－0.34， 95%CI （－0.44， －0.25）， P＜0.000 01] and insulin resistance assessed by homeostasis model [MD＝－0.38， 95%CI （－0.63， －0.13）， P＝0.003] were all significantly decreased in the treatment group. However， there was no statistically significant difference of probiotics therapy in the levels of tumor necrosis factor-α [MD＝－0.41， 95%CI （－1.29， 0.48）， P＝0.37]， interleukin-6 [MD＝0.39， 95%CI （ －0.10， 0.88）， P＝0.12]， high- sensitivity C-reactive protein [MD＝－0.30， 95%CI （－0.85，0.25）， P＝0.28]， high-density lipoprotein cholesterol [MD＝0.03， 95%CI （ －0.01， 0.06）， P＝0.10] and low-density lipoprotein cholesterol [MD＝－0.10， 95%CI （－0.27， 0.07）， P＝0.23] and body mass index [MD＝0.07， 95%CI （－0.26， 0.40）， P＝0.68]. Subgroup analysis based on different intervention measures showed that the levels of γ-glutamyl transferase， liver stiffness measurement， and homeostatic model assessment of insulin resistance in the synbiotic group were not significantly improved compared to the control group， with consistent results for the remaining outcomes. Egger’s test results showed no publication bias. CONCLUSIONS The probiotic therapy can regulate liver function indexes， liver stiffness measurement and insulin resistance levels in patients with NAFLD well.

Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study

BACKGROUND AND AIM@#Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD.@*METHODS@#This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD.@*RESULTS@#After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1.@*CONCLUSION@#Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease / 中山大学学报(医学科学版)

ObjectiveTo explore the expression of transcription factor KLF16 in nonalcoholic fatty liver disease （NAFLD） and its effect on lipid metabolism. MethodsAn animal model of NAFLD was constructed in mice induced by a high-fat diet. The mice were divided into normal diet group （ND） and high fat diet group （HFD）. NAFLD cell model was constructed by primary mouse liver cells induced by oleic acid. The cells were divided into control group （Control group） and oleic acid induction group （OA group）. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blot were used to detect KLF16 expression in NAFLD animal and cell models. In vitro and in vivo models of KLF16 knockdown were constructed by injection of adeno-associated virus （AAV） into mouse tail veins and transient transfection of cell siRNA. Hematoxylin-eosin staining （HE） and other methods were used to detect changes in lipid deposition in NAFLD models before and after KLF16 knockout. RT-qPCR was used to detect the expression of key genes of lipid metabolism in both cellular and animal NAFLD models before and after KLF16 knockdown. Western blot assay was used to detect the expression of endoplasmic reticulum stress protein in NAFLD model before and after KLF16 knockdown. ResultsThe expression level of KLF16 was up-regulated in HFD group and OA group， and lipid deposition was increased in OA group after KLF16 was depressed. There was no change in TC level in hepatocytes between groups （P>0.05）， and TG level was increased in different degrees （P<0.05， P<0.001）. At the same time， the change of KLF16 expression also caused the change of ER stress protein expression in OA group. ConclusionThe transcription factor KLF16 may alleviate lipid deposition in nonalcoholic fatty liver disease by endoplasmic reticulum stress.

Application study of non-alcoholic steatohepatitis based on radiomics of computed tomography / 中国现代医生

Objective To construct and validate a whole liver radiomics model based on computed tomography(CT)to identify patients with non-alcoholic steatohepatitis(NASH).Methods A total of 122 patients with nonalcoholic fatty liver disease treated in Zhejiang Provincial People's Hospital from June 2018 to December 2022 were retrospectively selected,including 52 patients with NASH.They were randomly divided into training group(n=85)and test group(n=37)according to a ratio of 7:3,and the liver plain scan images of each patient were selected to extract the radiomics features.The extracted features of the training group were dimensioned down and the radiomics signature was established.After that,a joint model was constructed with relevant clinical features to identify NASH patients,and the diagnostic effectiveness of the model was evaluated using receiver operating characteristic curve and test group data.Results The joint model was constructed based on age and radiomics labels.The diagnostic efficiency of the model for identifying NASH patients in training group and test group were 0.899 and 0.880,the specificity were 91.2%and 88.1%,and the sensitivity were 86.7%and 88.2%,respectively.In addition,the calibration curve also showed good calibration performance in training group and test group.Conclusion The joint model based on liver CT can quantitatively evaluate NASH,and is expected to provide a non-invasive evaluation tool for clinical use.

Histological findings and NAFLD/NASH Status in liver biopsies of patients subjected to bariatric surgery

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.

Metabolic dysfunction-associated steatotic liver disease prevalence and risk factors in inflammatory bowel disease in tertiary center

SUMMARY OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

Association between nonalcoholic steatohepatitis and high serum ferritin levels in type 2 diabetes mellitus

SUMMARY OBJECTIVE: The aim of this study was to assess the role of elevated serum ferritin levels in the onset, pathological progression and prognosis of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease has been rapidly increasing worldwide. Despite extensive research on the pathogenesis of nonalcoholic fatty liver disease, a lack of sufficient clinical research on the relationship between nonalcoholic fatty liver disease and serum ferritin levels remains. METHODS: We analysed 968 patients with type 2 diabetes mellitus who underwent liver ultrasound examination and had their serum ferritin levels measured. The presence of nonalcoholic fatty liver disease and advanced liver fibrosis was determined through abdominal ultrasound examination and the nonalcoholic fatty liver disease fibrosis score. RESULTS: Compared to that in the non-nonalcoholic fatty liver disease group, the presence of hyperferritinemia was significantly more common in the nonalcoholic fatty liver disease group (83.3 vs. 56.3%, p=0.005). When patients with nonalcoholic fatty liver disease were stratified by the nonalcoholic fatty liver disease fibrosis score, those with advanced liver fibrosis exhibited a higher prevalence of hyperferritinemia (56.3, 78.9, and 88.9% for none, simple steatosis, and advanced fibrosis, respectively; p for trend=0.002). In multivariate logistic regression, liver fibrosis was independently associated with hyperferritinemia (odds ratio [OR] 1.45; 95% confidence interval [CI] 1.18-2.02; p=0.014), and this association remained significant in male patients after adjusting for other risk factors (OR 2.66; 95% CI 1.43-5.48; p=0.026). CONCLUSION: Identifying nonalcoholic fatty liver disease patients at a risk of developing nonalcoholic steatohepatitis and advanced fibrosis is crucial for implementing timely interventions and improving patient outcomes. This study highlights the potential utility of serum ferritin levels as a serum biomarker for identifying nonalcoholic steatohepatitis patients and those at a risk of late-stage fibrosis, particularly in male patients with nonalcoholic fatty liver disease.

Helicobacter pylori e as doenças hepatobiliares: atualização 2023 / Helicobacter and hepatobiliary diseases: update 2023

ABSTRACT Helicobacter Pylori (H. pylori) is one of the main infectious causes of gastroduodenal diseases, however, its role in developing different extragastric diseases has been proven. The possible involvement of H. pylori in the pathogenesis of cardiovascular, metabolic, neurodegenerative, skin, and hepatobiliary diseases is suggested. The bacterium has been found in tissue samples from the liver, biliary tract, and gallstones of animals and humans. However, the role of H. pylori infection in the pathogenesis of liver and biliary diseases has not been finally established. The histopathological confirmation of the positive effect of H. pylori eradication is needed. In addition, there are discussions on the clinical significance of other Helicobacter species. The review presents the data available for and against the involvement of H. pylori in hepatobi­liary disease development and progression.

RESUMO Helicobacter pylori (H. pylori) é uma das principais causas infecciosas de doenças gastroduodenais, no entanto, seu papel no desenvolvimento de diferentes doenças extragástricas tem sido comprovado. Sugere-se o possível envolvimento do H. pylori na patogênese de doenças cardiovasculares, metabólicas, neurodegenerativas, cutâneas e hepatobiliares. A bactéria tem sido encontrada em amostras de tecido do fígado, trato biliar e cálculos biliares de animais e humanos. No entanto, o papel da infecção por H. pylori na patogênese de doenças do fígado e das vias biliares ainda não foi estabelecido definitivamente. A confirmação histopatológica do efeito positivo da erradicação do H. pylori é necessária. Além disso, existem discussões sobre a importância clínica de outras espécies de Helicobacter. A revisão apresenta os dados disponíveis a favor e contra o envolvimento do H. pylori no desenvolvimento e progressão das doenças hepatobiliares.

Effect and mechanism of matrine on steatosis Chang Liver cells induced by oleic acid / 中国药房

OBJECTIVE To investigate the effects of matrine （MT） on steatosis Chang Liver cell model induced by oleic acid （OA） and its possible mechanism. METHODS Chang Liver cells were divided into blank group， model group and MT low-dose， medium-dose group and high-dose groups （0.1， 0.5， 1.0 mmol/L）. Except for blank group， the other groups were treated with 1.0 mmol/L OA for 24 h to establish steatosis model， and MT groups were given corresponding concentrations of drugs for 24 h. The activities of steatosis Chang Liver cells were observed； the morphologies of intracellular lipid droplets were observed and lipid content was also determined. The contents of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）]， as well as mRNA and protein expressions of farnesoid X receptor （FXR）， cytochrome P450 7A1 （CYP7A1） and fibroblast growth factor 19 （FGF19） were all detected. RESULTS OA and MT had no significant effect on the activity of Chang Liver cells. After OA treatment， orange lipid droplets formed in cytoplasm； compared with blank group， relative lipid content and the levels of liver function indexes were increased significantly， while the mRNA and protein expressions of FXR， CYP7A1 and FGF19 were down-regulated significantly （P＜0.05）. After treatment of low， medium and high concentrations of MT， above indexes were all reversed significantly （P＜0.05）. CONCLUSIONS MT could significantly improve the lipid content and liver function indexes of steatosis Chang Liver cells induced by OA though regulating FXR/CYP7A1/ FGF19 signaling pathway.

Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Dendrobii Caulis mixture on cell inflammatory response and apoptosis in diabetic rat with non-alcoholic fatty liver disease（NAFLD） and its possible mechanism. MethodForty male SD rats were randomly divided into blank group and model group of type 2 diabetes mellitus（T2DM） with NAFLD according to body weight. The model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）， which was randomly divided into the model group， Dendrobii Caulis mixture group（16.67 g·kg-1·d-1） and metformin group（100 mg·kg-1·d-1） according to blood glucose and body weight， and 10 rats in each group. Rats in each group were administered by continuous gavage for 4 weeks， the blank and model groups were given saline by gavage at 10 mL·kg-1·d-1. Fasting blood glucose（FBG）， serum insulin（INS）， glycosylated serum protein（GSP）， triglyceride（TG）， total cholesterol（TC）， high density lipoprotein（HDL-C）， low density lipoprotein（LDL-C）， alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were detected in each group of rats. The liver tissues of rats in each group were stained with hematoxylin-eosin（HE） to observe the pathological changes， and the positive expressions of nuclear transcription factor（NF）-κB， NOD-like receptor heat protein structural domain-related protein 3（NLRP3）， interleukin（IL）-1β and tumor necrosis factor（TNF）-α were observed by immunohistochemistry. Western blot and fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of B-cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， Caspase-3 and NF-κB p65， NLRP3， IL-1β， TNF-α in liver tissue of rats in each group. ResultCompared with the blank group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels were increased， INS and HDL-C levels were decreased， Bax， Caspase-3， NLRP3， IL-1β， TNF-α protein and mRNA expression were increased in model group， the ratio of p-NF-κB/NF-κB protein increased， the expression of Bcl-2 protein and mRNA decreased， and the positive immunohistochemical expression of NF-κB， NLRP3， IL-1β and TNF-α increased， and the differences were statistically significant（P<0.01）. The morphological structure of the liver was disrupted， and obvious fat vacuoles were seen. Compared with the model group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels of Dendrobii Caulis mixture group and metformin group were decreased， INS and HDL-C levels were increased， and protein and mRNA expressions of Bax， Caspase-3， NLRP3， IL-1β and TNF-α were decreased， the protein ratio of p-NF-κB/NF-κB decreased， the expression of Bcl-2 protein and mRNA increased， and the positive immunohistochemical expressions of NF-κB， NLRP3， IL-1β and TNF-α decreased， and the differences were statistically significant（P<0.01）. The liver morphology and structure were relatively complete， and the fat vacuoles were reduced. ConclusionDendrobii Caulis mixture can inhibit cell apoptosis， reduce inflammatory response and alleviate liver injury in rats with T2DM and NAFLD， the mechanism may be related to inhibiting the activation of NF-κB pathway， blocking the activation of NLRP3 inflammatory vesicles， reducing IL-1β secretion， attenuating Caspase-3 activity and reducing the ratio of Bcl-2/Bax.

Association between Serum Uric Acid to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease Risk among Chinese Adults / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this case-control study was to explore the association between serum uric acid to high density lipoprotein cholesterol ratio (UHR) and the risk of nonalcoholic fatty liver disease (NAFLD) in Chinese adults.@*METHODS@#A total of 636 patients with NAFLD and 754 controls were enrolled from the Affiliated Hospital of Qingdao University, China, between January and December 2016. All patients completed a comprehensive questionnaire survey and underwent abdominal ultrasound examination and a blood test. NAFLD was diagnosed using ultrasonography after other etiologies were excluded. Logistic regression and restricted cubic spline model were conducted to evaluate the relationship of UHR with NAFLD risk.@*RESULTS@#The multivariable adjusted odds ratio (95% confidence interval, CI) for NAFLD in the highest versus lowest quartile of UHR was 3.888 (2.324-6.504). In analyses stratified by sex and age, we observed significant and positive associations between UHR and the risk of NAFLD in each subgroup. In analyses stratified by body mass index (BMI), a significant and positive association was found only in individuals with a BMI of ≥ 24 kg/m2. Our dose-response analysis indicated a linear positive correlation between UHR and the risk of NAFLD.@*CONCLUSION@#UHR is positively associated with the risk of NAFLD and may serve as an innovative and noninvasive marker for identifying individuals at risk of NAFLD.

Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis / 中国中药杂志

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

Research progress on chemical constituents of Schisandra chinensis and its effect on nonalcoholic fatty liver disease / 中国中药杂志

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.

Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives / 中华肝脏病杂志

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.