Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Caracterización clínico-epidemiológica de pacientes con enfermedad hepática esteatósica asociada a disfunción metabólica previa al trasplante en un hospital de cuarto nivel / Clinical-epidemiological characterization of patients with steatotic liver disease associated with metabolic dysfunction prior to transplantation in a fourth level hospital

Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) se ha convertido en la enfermedad hepática crónica más frecuente en los países occidentales, causando un aumento en los costos y en la ocupación hospitalaria. La caracterización integral previa al trasplante hepático en pacientes con MASLD es una gran interrogante, especialmente en nuestro medio. El objetivo del presente estudio fue realizar la caracterización clínico-epidemiológica de pacientes trasplantados por cirrosis hepática (CH) descompensada o carcinoma hepatocelular (CHC) asociado a MASLD. Metodología. Se desarrolló un estudio observacional retrospectivo, descriptivo, de corte transversal en el Servicio de Hepatología del Hospital Pablo Tobón Uribe en Medellín, Colombia. Se incluyeron pacientes mayores de 17 años, con diagnóstico de CH o de CHC asociado a MASLD que fueron trasplantados entre los años 2004 a 2017. Resultados. Se encontraron 84 pacientes que fueron trasplantados con esas características. La edad promedio de los pacientes fue de 59±10,5 con una mayor proporción significativa de hombres sobre mujeres, llegando casi al 70 %. Con relación a las comorbilidades, se encontró que el sobrepeso/obesidad, la hipertensión arterial y la diabetes mellitus tipo 2 fueron un hallazgo en el 44,1 %, 33,3 % y 33,3 %, respectivamente. Por otro lado, el 14,5 %, el 33,7 % y el 51,8 % presentaron un Child-Pugh A, B y C, respectivamente. La media del puntaje MELD fue de 18,9±6,26. Con respecto a las complicaciones de la cirrosis, el 77,4 % de los pacientes presentó ascitis, el 61,9 % encefalopatía hepática, el 36,9 % hemorragia del tracto digestivo superior y el 29,8 % peritonitis bacteriana espontánea. Conclusión. Los resultados expuestos mostraron nuestra experiencia en trasplante hepático en pacientes con CH y CHC asociado a MASLD. Se debe realizar una evaluación multidisciplinaria antes y después del trasplante en estos pacientes, haciendo especial énfasis en el manejo de la disfunción metabólica y sus componentes, entre los que se destacan la obesidad y la diabetes mellitus.

Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most frequent chronic liver disease in Western countries, causing increased costs and hospital occupancy. The comprehensive pre-transplant characterization in patients with MASLD is a major question, especially in our setting. The aim of the present study was to perform the clinical-epidemiological characterization of transplanted patients with decompensated liver cirrhosis (LC) or hepatocellular carcinoma (HCC) associated with MASLD. Methodology. A retrospective, descriptive, cross-sectional observational study was carried out in the Hepatology Department of the Pablo Tobón Uribe Hospital in Medellin, Colombia. Patients over 17 years of age, with a diagnosis of LC or HCC associated with MASLD who were transplanted between 2004 and 2017 were included. Results. We found 84 patients who were transplanted with these characteristics. The mean age of the patients was 59±10.5 with a significantly higher proportion of men over women, reaching almost 70%. Regarding comorbidities, overweight/obesity, arterial hypertension, and type 2 diabetes mellitus were found in 44.1%, 33.3%, and 33.3%, respectively. On the other hand, 14.5%, 33.7%, and 51.8% had Child-Pugh A, B, and C, respectively. The mean MELD score was 18.9±6.26. Regarding complications of cirrhosis, 77.4% of patients developed ascites, 61.9% hepatic encephalopathy, 36.9% upper gastrointestinal tract hemorrhage, and 29.8% spontaneous bacterial peritonitis. Conclusion. The above results showed our experience of liver transplantation in patients with LC and HCC associated with MASLD. A multidisciplinary evaluation should be performed before and after transplantation in these patients, with special emphasis on the management of metabolic dysfunction and its components, including obesity and diabetes mellitus.

Efecto del confinamiento por COVID-19 en la prevalencia de la enfermedad hepática esteatósica asociada a disfunción metabólica / Effect of COVID-19 lockdown on the prevalence of metabolic dysfunction-associated steatotic liver disease

Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) es una condición clínica frecuente, relacionada con el sobrepeso, la dislipidemia y la diabetes. Como estos factores de riesgo están a su vez asociados al sedentarismo y la ganancia de peso, se esperaría un impacto como resultado del confinamiento por COVID-19 en la prevalencia de dicha condición. Metodología. Estudio longitudinal retrospectivo en un panel de datos de 132 pacientes de 2017 a 2022, en donde fueron incluidos pacientes con una ecografía hepática y una valoración médica y paraclínica 1,5 años antes y después del periodo de confinamiento (25 de marzo de 2020 a 28 de febrero de 2021). El desenlace primario fue un cambio significativo en la prevalencia de la MASLD, y se utilizó un modelo exploratorio de regresión logística de efectos fijos con panel de datos para hallar los predictores de cambio. Resultados. En un total de 132 pacientes analizados, la prevalencia global de la MASLD antes (31 %; IC95%: 23-39) y después (35,6 %; IC95%: 27,4-43,8) del confinamiento por COVID-19 no cambió significativamente, sin embargo, en las mujeres sí hubo un aumento significativo (RR: 4; IC95%: 1,0004-16). Se encontró una marcada diferencia de prevalencia entre sexos (17 % en mujeres y 46 % en hombres; p=0,001). El confinamiento se asoció a incrementos en la masa corporal (diferencia: +1 kg; IC95%: 0,1-1,9), el colesterol LDL (diferencia: +9,7 mg/dL; IC95%: 4,9-14,4) y al diagnóstico de prediabetes (RR: 2,1; IC95%: 1,4-3,1). La MASLD se asoció positivamente a la preferencia nutricional por la comida rápida (p=0,047). Solo el índice de masa corporal resultó predictor independiente de MASLD (RR: 1,49; IC95%: 1,07-1,93). Conclusión. La prevalencia global de la MASLD no varió después del confinamiento por COVID-19, pero sí se incrementó en mujeres, y algunos de sus factores de riesgo también aumentaron significativamente. Se encontró equivalencia numérica entre la MASLD y la definición previa de la enfermedad. Se requiere un estudio local más grande para desarrollar y validar un mejor modelo predictor del cambio de la MASLD a través del tiempo.

Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common clinical condition, related to overweight, dyslipidemia and diabetes. As these risk factors are in turn associated with sedentary lifestyle and weight gain, an impact as a result of the COVID-19 confinement on the prevalence of MASLD would be expected. Methodology. Retrospective longitudinal study in a data panel of 132 patients from 2017 to 2022. Patients with a liver ultrasound and a medical and paraclinical assessment 1.5 years before and after the confinement period (March 25, 2020 to February 28, 2021) were included. The primary outcome was a significant change in the prevalence of MASLD, and an exploratory fixed-effects logistic regression model with panel data was used to find predictors of change. Results. In a total of 132 patients analyzed, the overall prevalence of MASLD before (31%, 95%CI: 23-39) and after (35.6%, 95%CI: 27.4-43.8) confinement by COVID-19 did not change significantly, however, in women there was a significant increase (RR: 4, 95%CI: 1.0004-16). A marked difference in prevalence was found between sexes (17% in women and 46% in men; p=0.001). Confinement was associated with increases in body mass (difference: +1 kg, 95%CI: 0.1-1.9), LDL cholesterol (difference: +9.7 mg/dL, 95%CI: 4.9-14.4) and the diagnosis of prediabetes (RR: 2.1, 95%CI: 1.4-3.1). MASLD was positively associated with nutritional preference for fast food (p=0.047). Only body mass index was an independent predictor of MASLD (RR: 1.49, 95%CI: 1.07-1.93). Conclusion. The overall prevalence of MASLD did not change after the COVID-19 lockdown, but it did increase in women, and some of its risk factors also increased significantly. Numerical equivalence was found between MASLD and the previous definition of the disease. A larger local study is required to develop and validate a better predictor model of MASLD change over time.

Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison

ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

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.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation

SUMMARY OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Frequency of fibrosis in patients with incidentally detected hepatosteatosis

SUMMARY OBJECTIVE: In this study, we aimed to elucidate fibrosis in patients who visited our outpatient clinic with complaints such as abdominal pain and dyspepsia and who had fatty liver by ultrasound imaging. METHODS: A total of 119 patients who were admitted to the gastroenterology outpatient clinic of our institution with incidentally detected hepatosteatosis on ultrasound imaging were included in the study. Patients with hepatosteatosis were examined for fibrosis with the FibroScan-502-touch (Echosens, Paris, France) elastic tissue ultrasonography device. The effects of these parameters on hepatosteatosis and possible fibrosis degree were investigated. RESULTS: No fibrosis was detected in 75 (63.02%) patients with hepatosteatosis on ultrasound imaging, 20 (10.05%) F1, 22 (18.48%) F2, 1 (0.8%) F3, and 0.1 (0.8%) F4. Accordingly, as the degree of steatosis increases in patients with incidentally detected hepatosteatosis, the degree and frequency of fibrosis increase with statistical significance (p<0.05). A statistically significant difference was found between the alanine transaminase increase and the hepatosteatosis degree (p=0.028). The median value of gamma-glutamyltransferase was 15 U/L in S0, 18.5 U/L in S1, 22 U/L in S2, and 26 U/L in S3 (p<0.047). CONCLUSION: To date, no research exists on fibrosis in patients with incidental hepatosteatosis. The outcomes of this study elaborated that patients with hepatosteatosis in the community could be detected at least at an early stage by following up and diagnosing them with serum markers before they progress to end-stage fibrosis.

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.

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.

Mechanism of amino acid metabolism in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is one of the most prevalent chronic liver diseases in the world， affecting about one quarter of the global population， and it is estimated that NAFLD will become the main indication for liver transplantation by 2030. NAFLD can lead to significant abnormalities in the levels of a variety of amino acids including branched-chain amino acids， thereby promoting the development and progression of NAFLD. These results suggest that in addition to glucose and lipid metabolism， amino acid metabolism also plays an important role in the progression of NAFLD. In order to systematically understand the role and mechanism of amino acid metabolism in NAFLD， this article reviews the research advances in amino acid metabolism in NAFLD. This article aims to explore the role and mechanism of amino acid metabolism in the progression of NAFLD， so as to provide ideas and a theoretical basis for clinical prevention and treatment.

Mechanism of action of traditional Chinese medicine in treatment of nonalcoholic fatty liver disease based on intestinal microecology / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is a multisystem disease associated with obesity， insulin resistance， and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD， and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota， the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD， and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota， in order to provide new ideas for the treatment of NAFLD.

Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease （NAFLD） induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 （NLRP6）. MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， high-fat diet （HFD） group， and Xiayuxue decoction-HFD group （XYXD group）， with 5 mice in each group. Liver function parameters （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］） and blood lipid metabolic indicators （triglycerides ［TG］ and total cholesterol ［TC］） were measured； HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition； quantitative real-time PCR was used to measure the expression levels of inflammatory factors （tumor necrosis factor-α ［TNF-α］， interleukin-1β ［IL-1β］， interleukin-18 ［IL-18］， and NLRP6） in liver tissue； Western blot was used to measure the protein expression levels of NLRP6， nuclear factor-kappa B （NF-κB）， and NF-κB p65； immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid （PA）， lipopolysaccharide， and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group， the HFD group had significant increases in the serum levels of ALT， AST， TC， and TG （all P<0.05）. Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score （P<0.05）， and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 （all P<0.05）. Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression， there was a significant increase in phosphorylated NF-κB p65 （P<0.05）. Compared with the HFD group， Xiayuxue decoction effectively improved liver inflammation， upregulated the expression of NLRP6， and downregulated phosphorylated NF-κB p65 in HFD mice （all P<0.05）. After Raw264.7 cells were treated with PA， NLRP6 was downregulated to promote the progression of inflammation （P<0.05）， and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB （P<0.05）. ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD， possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

Protective effect of Genistein against nonalcoholic fatty liver disease in ovariectomized mice and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the protective effect of Genistein against nonalcoholic fatty liver disease （NAFLD） in ovariectomized （OVX） mice and its mechanism. MethodsA total of 40 female C57BL/6 mice， aged 6 weeks， were used to establish an OVX mouse model， and then they were randomly divided into blank group， 4-week model group， 6-week model group， 8-week model group， and 10-week model group， with 8 mice in each group. Under the same environmental conditions， the mice were given high-fat diet for modeling， and pathological examination showed that NAFLD was successfully induced by 10-week high-fat diet. Another 40 female C57BL/6 mice， aged 6 weeks， were randomly divided into blank group， sham operation group （Sham group）， OVX group， OVX+L-Genistein （4 mg/kg body weight） group， and OVX+H-Genistein （8 mg/kg body weight） group. The mice in the Sham group were given the same procedure of OVX， without the ligation of the ovarian artery and the resection of the ovary. The mice in the blank group were given normal diet， and those in the other groups were given high-fat diet. Genistein was dissolved in DMSO， and the mice in the Sham group and the OVX group were treated with solvent solution alone by gavage， once a day for 10 consecutive weeks. Body weight and visceral index were recorded， and the mice were sacrificed to collect serum and liver tissue. Kits were used to measure the activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） and the serum levels of triglyceride （TG） and total cholesterol （TC）， and HE staining and oil red O staining were used to observe liver histopathology； Western blot was used to measure the protein expression levels of sterol regulatory element-binding protein 1c （SREBP-1c） and peroxisome proliferator-activated receptor alpha （PPARα） associated with lipid metabolism in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett-t test was used for further comparison between two groups. ResultsAfter 10 weeks of high-fat diet， the OVX+L-Genistein group and the OVX+H-Genistein group had significantly lower body weight， liver index， and liver tissue weight （all P<0.05）. In addition， Genistein significantly downregulated the serum levels of TC and TG （P<0.05） and reduced the activities of serum AST and ALT （P<0.05）. HE and oil red O staining showed that compared with the OVX group， the OVX+L-Genistein group and the OVX+H-Genistein group had a significant reduction in the accumulation of lipid droplets. Western blot showed that after Genistein intervention， there was a significant reduction in the protein expression level of SREBP-1c and a significant increase in the protein expression level of PPARα （P<0.05）. ConclusionGenistein exerts a protective effect against NAFLD in OVX mice possibly by regulating the expression of SREBP-1c and PPARα， thereby promoting fatty acid oxidation and inhibiting liver lipid synthesis.

Association of polymorphisms of the acetyl-coA acetyltransferase 1 gene and the melatonin receptor 1B gene with the susceptibility to nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Value of Fetuin-A， Fetuin-B， and insulin resistance index in predicting nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the value of serum Fetuin-A and Fetuin-B combined with Homeostasis Model Assessment of Insulin Resistance （HOMA-IR） in predicting nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 120 patients with NAFLD who attended Department of Gastroenterology， The First Affiliated Hospital of Dali University， from June 2020 to June 2021， and 120 healthy individuals who underwent physical examination at Physical Examination Center during the same period of time were enrolled as subjects， and clinical data were collected from all subjects. The serum levels of Fetuin-A and Fetuin-B were measured. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the multivariate Logistic regression analysis was used to assess the risk factors for NAFLD. The receiver operating characteristic （ROC） curve was plotted to evaluate the predictive efficacy of Fetuin-A and Fetuin-B combined with HOMA-IR in NAFLD patients. ResultsCompared with the healthy control group， the NAFLD group had significantly higher levels of body mass index， systolic blood pressure， diastolic blood pressure， alanine aminotransferase， aspartate aminotransferase， fasting blood glucose， fasting insulin， triglycerides， HOMA-IR， Fetuin-A， and Fetuin-B （all P<0.05）. The multivariate Logistic regression analysis showed that Fetuin-A （odds ratio ［OR］=1.010， 95% confidence interval ［CI］： 1.001‍‍‍ ‍‍‍—‍‍‍ ‍‍1.020， P<0.05）， Fetuin-B （OR=1.113， 95%CI： 1.021‍ ‍‍—‍‍ ‍1.214， P<0.05）， and HOMA-IR （OR=24.053， 95%CI： 2.624‍ ‍‍—‍‍ ‍220.470， P<0.05） were independent risk factors for NAFLD. The ROC curve analysis showed that Fetuin-A， Fetuin-B or HOMA-IR alone had an area under the ROC curve （AUC） of 0.637 （95%CI： 0.551‍ ‍—‍ ‍0.722）， 0.853 （95%CI： 0.796‍ ‍—‍ ‍0.912）， and 0.837 （95%CI： 0.763‍ ‍—‍ ‍0.912）， respectively， and Fetuin-A combined with Fetuin-B， Fetuin-A combined with HOMA-IR， and Fetuin-B combined with HOMA-IR had an AUC of 0.853 （95%CI： 0.795‍ ‍—‍ ‍0.911）， 0.843 （95%CI： 0.770‍ ‍—‍ ‍0.916）， 0.922 （95%CI： 0.877‍ ‍—‍ ‍0.967）， respectively， while the combination of these three indicators had an AUC of 0.922 （95%CI： 0.877‍ ‍—‍ ‍0.966）. ConclusionFetuin-A and Fetuin-B have a certain value in predicting NAFLD， and Fetuin-B combined with HOMA-IR tends to have a higher predictive value.

Association between urinary thallium and nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association between urinary thallium （TL） and nonalcoholic fatty liver disease （NAFLD）. MethodsRelated data were collected from the registered participants aged ≥18 years in National Health and Nutrition Examination Survey from 2017 to 2020， with th exclusion of the individuals with a lack of liver transient elastography data and urinary TL indicators and those with hepatitis B， hepatitis C or significant alcohol consumption. A total of individuals were divided into NAFLD group and non-NAFLD group. Urinary TL level was quantitatively measured using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and online solid-phase extraction combined with isotope dilution. The two groups were compared in terms of age， sex， race， marital status， education， family income poverty impact ratio （FMPIR）， body mass index （BMI）， smoking， alcohol consumption， diabetes mellitus （DM）， hypertension （HTN）， hyperlipidemia （HL）， and urinary TL level. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Descriptive analysis， multivariable Logistic regression， restricted cubic spline regression analysis， subgroup analysis， and interaction analysis were conducted to investigate the risk association between urinary TL and NAFLD. ResultsA total of 2 511 individuals were included， with 1 612 （64.20%） in the NAFLD group and 899 （35.80%） in the non-NAFLD group， and the NAFLD group had a significantly higher urinary TL level than the non-NAFLD group ［0.18 （0.11‍ ‍— ‍0.26）μg/L vs 0.16 （0.09 — ‍0.25）μg/L， Z=-2.76， P=0.01］. After adjustment for the covariates of age， sex， race， education， marital status， FMPIR， BMI， smoking， alcohol consumption， DM， HTN， and HL， the urinary TL Q4 group had a significant increase in the risk of NAFLD （odds ratio ［OR］=1.90， 95% confidence interval ［CI］： 1.48‍ — ‍2.44， P<0.01）. There was a positive dose-response relationship （P<0.01） and a non-linear relationship （P<0.01） between urinary TL and the risk of NAFLD. A significant interaction was observed between urinary TL and smoking/BMI （P<0.05）. For individuals taking ≥100 cigarettes in their lifetime， the risk of NAFLD was increased by 50% for every quartile increase in urinary TL （OR=1.50， 95%CI： 1.24‍ — ‍1.80）， and for individuals taking<100 cigarettes in their lifetime， the risk of NAFLD was increased by 20% for every quartile increase in urinary TL （OR=1.20， 95%CI： 1.03‍ — ‍1.40）； for individuals with a BMI of ≥30 kg/m2， the risk of NAFLD was increased by 30% for every quartile increase in urinary TL （OR=1.30， 95%CI： 1.05‍ — ‍1.70）， with a statistical significance （P<0.05）. ConclusionUrinary TL level is significantly associated with the risk of NAFLD.

Application of magnetic resonance imaging-proton density fat fraction in liver fat quantification / 临床肝胆病杂志

Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.

Role of Akkermansia muciniphila in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

Application of Mendelian randomization analysis in exploring the etiology of nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is an abnormal lipid metabolic disorder of the liver characterized by accumulation of a large amount of lipids in the liver， and it is currently the most common liver disease around the world. Mendelian randomization （MR） incorporates genomic data into traditional epidemiological study designs to infer the causal relationship between exposure factors and disease risk. In recent years， MR has been widely used in studies on inference of the etiology of NAFLD. This article systematically summarizes the advances in the application of MR in NAFLD research， so as to provide new ideas for understanding the nature of the disease and scientific interventions.

Epidemiology and clinical outcome of chronic hepatitis B virus infection and metabolic dysfunction / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is a worldwide public health issue and a leading cause of liver fibrosis， liver cirrhosis， liver failure， and primary liver cancer in China. The incidence rate of nonalcoholic fatty liver disease （NAFLD） is gradually increasing with the improvement in the living standards of people and the changes in dietary structure. Population-based studies have found that HBV infection can influence the development of NAFLD， but the mechanism remains unknown. Hepatic steatosis can also influence the expression of HBV serum pathogenic indicators， and its combination with NAFLD and other metabolic dysfunction diseases can increase the risk of liver fibrosis， liver cirrhosis， and liver cancer. Chronic HBV infection is closely associated with metabolic dysfunction， and more studies are needed in the future to better understand related mechanisms， so as to provide a theoretical foundation for clinical diagnosis and treatment.