Protective effect of Zhizi Dahuang decoction in a mouse model of alcoholic liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. 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. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.

Clinical features of non－B， non－C hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the change in the proportion of non－B， non－C hepatocellular carcinoma （NBNC－HCC） in hepatocellular carcinoma， and to compare and analyze the clinicopathological features of NBNC－HCC. MethodsA total of 3 090 patients with hepatocellular carcinoma （HCC） who were diagnosed in Sichuan Provincial People’s Hospital from January 2011 to December 2021 were enrolled， and according to the hepatitis markers， they were divided into hepatitis virus infection－associated HCC group with 2 472 patients and NBNC－HCC group with 618 patients. According to the liver disease and metabolic risk factors， the NBNC－HCC group was further divided into metabolic disorder HCC group with 289 patients， alcoholic liver disease （ALD）－associated HCC group with 174 patients， and other HCC group with 155 patients. General information， laboratory markers， and pathological findings were collected from all HCC patients. The Mann－Whitney U test was used for comparison of continuous data between two groups， and the Kruskal－Wallis H test was used for comparison between three groups； the chi－square test was used for comparison of categorical data between groups， and the chi－square trend test was used to investigate the trend of the change in the proportion of NBNC－HCC in HCC. ResultsThe proportion of patients with NBNC－HCC in HCC increased from 13.7% in 2011 to 20.1% in 2021 （χ2=5.529， P=0.019）， and compared with the hepatitis virus infection－associated HCC group， the NBNC－HCC group had a significantly higher proportion of patients with diabetes （28.0% vs 10.3%， χ2=129.482， P<0.001） or hypertension （33.2% vs 15.2%， χ2=105.079， P<0.001）， a significantly lower proportion of patients with liver cirrhosis （44.5% vs 68.4%， χ2=122.563， P<0.001） or vascular invasion （20.4% vs 29.6%， χ2=7.749， P=0.005）， and a significantly higher body mass index （BMI） （Z=－4.015， P<0.001）. Compared with the ALD－HCC group， the metabolic disorder HCC group had a significantly higher BMI， a significantly lower FIB－4 index， and a significantly lower proportion of patients with liver cirrhosis （all P<0.05）. ConclusionThere is a tendency of increase in the proportion of patients with NBNC－HCC in HCC， and NBNC－HCC often coexists with metabolic risk factors such as obesity， diabetes， and hypertension. Patients in the metabolic disorder HCC group may develop liver cancer in the absence of liver cirrhosis or in the early stage of liver fibrosis.

Role of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway in alcoholic liver disease / 临床肝胆病杂志

The incidence rate of alcoholic liver disease (ALD) is increasing year by year China, and there is a gradual increase in disease burden among Chinese people. Oxidative stress response in hepatocytes is an important pathogenic mechanism of ALD. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is an important endogenous anti-oxidative stress pathway in the body, and Nrf2 is activated in response to oxidative stress and exerts its transcriptional activity to induce high HO-1 expression. HO-1 is an important oxidative stress response protein and plays a role in anti-inflammation, anti- oxidation, and cell apoptosis regulation together with heme hydrolysis products (bilirubin, carbon monoxide, and iron). This article reviews the research advances in the role of the Nrf2/HO-1 signaling pathway in ALD in recent years, so as to find a theoretical basis for the development and progression of ALD and an entry point for treatment.

Effectiveness of increasing alcohol excise taxes in the management of alcohol-associated liver disease in China / 临床肝胆病杂志

Increasing alcohol excise taxes has been confirmed by the World Health Organization as the most cost-effective public policy for reducing alcohol consumption at the population level. In recent years, studies in foreign countries have believed that increasing alcohol excise taxes can improve the burden of alcohol-associated liver disease (ALD), but it is still unclear whether this policy is applicable to ALD management in China. Therefore, with reference to related research evidence in China and globally, this article analyzes the key factors influencing the effectiveness of the policy of increasing alcohol excise taxes from the perspective of ALD management in China, including tax shifting, price elasticity of demand, and unrecorded alcohol, and introduces other public policies that help curb ALD. We think that increasing alcohol excise taxes is currently a useful but not effective policy for improving the burden of ALD in China.

Research advances in the role of / 临床肝胆病杂志

Alcoholic liver disease (ALD) is one of the most common chronic liver diseases worldwide and includes the different stages of steatosis, steatohepatitis, fibrosis, and liver cirrhosis. Enterococcus faecalis is a common bacterium for nosocomial infection and has a significant impact on the prognosis of patients with alcoholic hepatitis. This review mainly introduces the pathogenesis of ALD and the pathogenic mechanism of E. faecalis , summarizes the research advances in E. faecalis in ALD, and briefly describes the detection and treatment methods for E. faecalis infection in clinical practice. Since there is an extremely high mortality rate in ALD patients with lytic E. faecalis infection, an in-depth understanding of E. faecalis has become an important issue nowadays.

Ursolic acid in / 临床肝胆病杂志

Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. 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. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.

Mechanism of action of Dange Jiecheng decoction in a rat model of alcoholic liver disease based on the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling pathway / 临床肝胆病杂志

Objective To investigate the therapeutic effect of Dange Jiecheng decoction on a rat model of alcoholic liver disease (ALD) and the anti-oxidative stress mechanism of Dange Jiecheng decoction. Methods A total of 96 Sprague-Dawley rats were randomly divided into blank group with 13 rats and ALD group with 83 rats, and the rats in the ALD group were given liquor by gavage to establish a model of ALD. Then the ALD group was randomly divided into model group, high-dose Dange Jiecheng decoction group (24 g/kg), low-dose Dange Jiecheng decoction group (6 g/kg), and Yiganling tablet group (21 mg/kg), with 17 rats in each group. The rats in the blank group and the model group were given normal saline by gavage, and those in the other groups were given corresponding drugs by gavage, for 4 consecutive weeks. HE staining was used to observe the pathological changes of liver tissue; Western blot was used to measure the contents of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver tissue; quantitative real-time PCR was used to measure the mRNA expression levels of Keap1 and HO-1 in liver tissue. 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. Results Compared with the blank group, the model group had disordered arrangement of hepatocytes with necrosis, massive inflammatory cell infiltration, and a large number of lipid droplet vacuoles, significant increases in the protein and mRNA expression levels of Keap1 ( P < 0.05), and significant reductions in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Compared with the model group, the high- and low-dose Dange Jiecheng decoction groups and the Yiganling tablet group had ordered arrangement of hepatocytes, reductions in hepatocyte necrosis and inflammatory cells, and occasional lipid droplet vacuoles, as well as significant reductions in the protein and mRNA expression levels of Keap1 ( P < 0.05) and significant increases in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Conclusion By regulating the Keap1/Nrf2 signaling pathway, Dange Jiecheng decoction can promote the nuclear import of Nrf2, upregulate the expression of HO-1, and alleviate oxidative stress response, thereby exerting a protective effect on ALD rats.

Role of A-kinase anchor protein 12 in chronic liver diseases / 临床肝胆病杂志

A-kinase anchor protein 12 (AKAP12) is a scaffold protein that improves the specificity and efficiency of spatio-temporal signals by assembling intracellular signal proteins into specific complexes. In recent years, the role of AKAP12 in chronic liver diseases has attracted more and more attention. This article introduces the physiological functions of AKAP12 and reviews the role of AKAP12 in chronic liver diseases, in order to lay a foundation for the use of AKAP12 small molecule as a new therapeutic target for chronic liver diseases.

Alcoholic foamy degeneration: an unusual presentation of the alcoholic liver disease diagnosed on autopsy

ABSTRACT Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.

Caracterización de pacientes con hepatopatías crónicas de etiología alcohólica mediante ecografía Doppler. Cienfuegos, 2020 / Characterization of patients with chronic liver disease of alcoholic etiology by Doppler ultrasound. Cienfuegos, 2020

RESUMEN Fundamento las hepatopatías crónicas constituyen enfermedades frecuentes a nivel mundial. La cirrosis hepática, cuya etiología más frecuente es el alcoholismo, representa el final de las lesiones hepáticas difusas crónicas y progresivas. Objetivo caracterizar los pacientes con hepatopatías crónicas alcohólicas mediante ecografía Doppler. Métodos se realizó un estudio descriptivo, de serie de casos, en 36 pacientes con diagnóstico clínico endoscópico y/o laparoscópico hepatopatías crónicas de etiología alcohólica, en el Hospital General Universitario Dr. Gustavo Aldereguía Lima, de Cienfuegos, en el período comprendido de enero a diciembre de 2020. Además de la edad y el sexo, se analizaron variables ecográficas según ecografía bidimensional (modo B) y Doppler. Resultados tuvieron mayor representatividad los pacientes masculinos y fue más numeroso el grupo etario de 42 a 51 años. El hígado y el bazo fueron de tamaño normal en la mayoría de los casos (44,5 % y 58,4 %, respectivamente). El hígado mostró ecoestructura predominantemente heterogénea (27,7 %) y nodular (58,4 %). Atendiendo al calibre de la porta extrahepática y de la vena esplénica, predominó la normalidad, ambas con 58,4 %. La ascitis, el derrame pleural y la circulación colateral no mostraron una frecuencia alta. Prevaleció la dirección de flujo hepatopedal (72,3 %) y velocidad de la porta normal (77,8 %). Conclusión en pacientes con hepatopatías crónicas de etiología alcohólica resulta de vital importancia la atención médica oportuna. La ecografía Doppler complementa la información morfológica aportada por la ecografía convencional.

ABSTRACT Background chronic liver diseases are frequent diseases worldwide. Liver cirrhosis, whose most frequent etiology is alcoholism, represents the end of chronic and progressive diffuse liver lesions. Objective to characterize patients with chronic alcoholic liver disease by Doppler ultrasound. Methods a descriptive case series study was carried out in 36 patients with clinical endoscopic and/or laparoscopic diagnosis of chronic hepatopathies of alcoholic etiology, at the Dr. Gustavo Aldereguía Lima General University Hospital, Cienfuegos, from January to December 2020. In addition to age and sex, ultrasound variables were analyzed according to two-dimensional ultrasound (B-mode) and Doppler. Results male patients were more representative and the age group from 42 to 51 years old was more numerous. The liver and spleen were of normal size in most cases (44.5% and 58.4%, respectively). The liver showed predominantly heterogeneous (27.7%) and nodular (58.4%) echostructure. Considering the caliber of the extrahepatic portal vein and the splenic vein, normality prevailed, both with 58.4%. Ascites, pleural effusion and collateral circulation did not show a high frequency. Hepatopedal flow direction (72.3%) and normal portal vein velocity (77.8%) prevailed. Conclusion in patients with chronic liver diseases of alcoholic etiology, timely medical care is of vital importance. Doppler ultrasound complements the morphological information provided by conventional ultrasound.

Role of Takeda G protein-coupled receptor-5 in non-viral liver diseases / 临床肝胆病杂志

Non-viral liver diseases mainly include nonalcoholic fatty liver disease, alcoholic liver disease, autoimmune liver disease, and cholestatic liver disease, and the prevalence rate of non-viral liver diseases tends to increase in recent years. Takeda G protein-coupled receptor-5 (TGR5) belongs to the G protein-coupled receptor superfamily and is activated by primary and secondary bile acids. TGR5 plays an important regulatory role in bile acid homeostasis, basal metabolism, energy balance, and alleviation of inflammatory response and is a potential therapeutic target for many diseases. An increasing number of evidence has shown that TGR5 exerts a protective effect on the liver by improving bile acid and glycolipid metabolism in liver, alleviating liver inflammation, and reducing liver steatosis. This article reviews the recent advances in the basic research on TGR5 in the field of non-viral liver diseases, so as to facilitate the development of the research on TGR5.

Role of interleukin-1β in the pathogenesis of alcoholic liver disease / 临床肝胆病杂志

Alcoholic liver disease (ALD) has become the second largest liver disease after viral liver disease in China. Chronic alcohol exposure increases the production of proinflammatory factors including interleukin-1β (IL-1β), which is closely associated with the main symptoms of alcoholic hepatitis such as pyrexia and elevated white blood cell count. This article introduces the production and function of IL-1β; in ALD, it promotes hepatic steatosis and inflammation by acting on liver parenchymal cells and nonparenchymal cells and accelerates liver fibrosis by regulating the proliferation of hepatic stellate cells. It is pointed out that interference with the IL-1β pathway may become one of the treatment strategies for ALD in the future.

Influence of high-density lipoprotein cholesterol on the prognosis of patients with alcohol-related hepatocellular carcinoma after radical treatment / 临床肝胆病杂志

ObjectiveTo investigate the association of high-density lipoprotein cholesterol (HDL-C) with the prognosis of patients with alcohol-related hepatocellular carcinoma (HCC) after radical treatment. MethodsA retrospective analysis was performed for the clinical data of 43 patients with alcohol-related HCC who were admitted to The Fifth Medical Center of Chinese PLA General Hospital and underwent radical treatment from January 2008 to July 2015, and according to HDL-C level, the patients were divided into normal group with 26 patients and abnormal group with 17 patients. The two groups were compared in terms of basic information, laboratory markers, imaging indices, Barcelona Clinic Liver Cancer tumor stage, and Child-Pugh class of liver function. The t-test test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for comparison between groups. Univariate and multivariate Cox proportional hazards models were used to analyze independent risk factors for prognosis. ResultsThere was a significant difference in prealbumin between the two groups (162.38±60.86 mg/L vs 120.06±64.08 mg/L, t=2.184, P=0.035). Number of tumors (hazard ratio ［HR］=2.839, 95%confidence interval ［CI］: 1.120~7.200,P=0.028), tumor size (HR=2.634, 95%CI: 1.062~6.529,P=0037), and HDL-C level (HR=2.400, 95%CI: 1.040~5.537,P=0.040) were independent risk factors for the overall survival of patients with alcohol-related HCC. There were significant differences in 1-, 3-, and 5-year cumulative survival rates between the normal group and the abnormal group (88.5%/72.4%/55.7% vs 70.6%/43.7%/17.5%, χ2=5.881, P=0.015). ConclusionThe reduction in HDL-C level might indicate poor prognosis of patients with alcohol-related HCC.

Application effect of timing theory in alcohol abstinence intervention for patients with alcoholic liver disease / 中国实用护理杂志

Objective:To explore the effect of alcohol abstinence intervention based on timing theory on patients with alcoholic liver disease.Methods:A total of 106 patients with alcoholic liver disease hospitalized in the Department of liver disease of Taian Medical District, 960th Hospital of Chinese PLA from July 2018 to June 2019 were selected by convenience sampling method and divided into observation group and control group by random digits table method, 53 cases in each group. The control group received routine nursing, and through the improvement of patients' cognition and support system, implemented short abstinence intervention during hospitalization; the observation group received abstinence intervention based on timing theory on the basis of the control group intervention. At 1 month and 6 months after discharge, the differences of rehydration rate, alcohol dependence and physical and mental status between the two groups were compared.Results:Finally, 49 cases in the control group completed the study, and 51 cases in the observation group completed the study. The rehydration rates of the observation group were 21.57%(11/51) and 15.69%(8/51) respectively at 1 month and 6 months after discharge, while those of the control group were 40.82%(20/49) and 36.73%(18/49) respectively at 1 month and 6 months after discharge. The difference was statistically significant ( χ2 values were 4.328, 5.754, P<0.05). The alcohol dependence scores were 0(2,3), 0(1,2) in the observation group and 2(0,3), 3(1,4) in the control group at 1 month and 6 months after discharge, and the difference was statistically significant ( Z values were -6.719, -7.345, P<0.01). There was no significant difference in the score of Symptom Checklist-90(SCL-90) before intervention and 1 month after discharge between the two groups ( P>0.05). Six months after discharge, the score of SCL-90 was 8.26 ± 1.37 in the observation group and 10.11 ± 1.68 in the control group, and the difference was statistically significant( t value was 6.046, P<0.01). Conclusions:The application of timing theory in alcohol abstinence of patients with alcoholic liver disease can significantly reduce the relapse rate and the degree of alcohol dependence of patients with alcoholic liver disease, improve the physical and mental state of patients.

Research progress on the protective mechanism of resveratrol on alcoholic liver disease / 中国医师杂志

The causes of more than 200 diseases are related to alcoholism, which can cause diseases in all systems of the body. As the place of alcohol absorption and metabolism, the damage of gastrointestinal tract and liver caused by excessive drinking can not be ignored. Alcohol can produce strong hepatotoxicity, resulting in intestinal microbial disorders. Resveratrol is a kind of natural polyphenols which widely exist in grapes, peanuts, nuts and other foods. It has many functions that are beneficial to human health, such as liver protection. Therefore, we reviewed the mechanism of the protective effect of resveratrol on alcoholic liver disease and proposed that intestinal microorganisms could be a potential research target for resveratrol in the prevention of alcoholic liver disease.

Comparison of tru-cut biopsy and fine-needle aspiration cytology in an experimental alcoholic liver disease model

SUMMARY INTRODUCTION Liver biopsies such as tru-cut (sharp needle) and fine-needle aspiration cytology (FNAC) are the most commonly preferred techniques to detect the grade and stage of certain liver diseases. In this study, we aimed to compare the efficiency of USG-guided tru-cut biopsy and fine-needle aspiration cytology in an experimental alcoholic liver disease model. METHODS Thirty-six female Wistar albino rats, 4-6 months old, and weighing from 190 to 250 g, were used in this study. The animals were randomly divided into six equal groups: G1 (control), G2 (tru-cut control), G3 (FNAC control), G4 (Alcoholic liver disease model), G5 (Alcoholic liver disease model + FNAC), and G6 (Alcoholic liver disease model + tru-cut biopsy). After a histopathological evaluation by light microscopy, the sensitivity, specificity, positive and negative predictive values of FNAC and tru-cut biopsy for the diagnosis of liver lesions were calculated. RESULTS No pathology was detected in G1 except for mild congestion. On the other hand, hepatocyte damage, periportal inflammation, congestion, and fatty changes were detected in all liver tissues of the alcoholic liver disease groups. The sensitivity of hepatocyte damage, inflammation, congestion, and fatty change parameters for FNAC were 33.3%, 80%, 0%, and 0%, respectively, while the sensitivity of the same variables for tru-cut were 66.7%, 40%, 100%, and 20%, respectively. DISCUSSION Both techniques were superior in some aspects. FNAC can be an attractive alternative to tru-cutbiopsy and applied in routine practice in the diagnosis of non-tumoral liver diseases.

RESUMO INTRODUÇÃO Biópsias hepáticas tais como por agulha tru-cut e por citologia aspirativa por agulha fina (CAAF) são as técnicas frequentemente preferidas para detectar o grau e o estágio de certas doenças hepáticas. Neste estudo, nosso objetivo foi comparar a eficiência da biopsia com agulha tru-cut guiada por ultrassom e a citologia aspirativa por agulha fina em um modelo experimental de doença hepática alcoólica. MÉTODOS Trinta e seis ratos Wistar albinos fêmeas, de 4 a 6 meses de idade e pesando entre 190 e 250g, foram utilizados neste estudo. Os animais foram divididos aleatoriamente em seis grupos: G1 (controle), G2 (controle tru-cut), G3 (CAAF), G4 (modelo de doença hepática alcoólica), G5 (modelo de doença hepática alcoólica + CAAF) e G6 (modelo de doença hepática alcoólica + biópsia tru-cut). Após uma avaliação histopatológica por microscopia de luz, foram calculados a sensibilidade, especificidade e os valores preditivos positivos e negativos da CAAF e biópsia por tru-cut para o diagnóstico de lesões hepáticas. RESULTADOS Nenhuma patologia foi detectada no G1, apenas leve congestão. Por outro lado, detectamos danos nos hepatócitos, inflamação periportal, congestão e alterações nos ácidos graxos nos tecidos hepáticos de todos os grupos de doença hepática alcoólica. As sensibilidades encontradas para os danos nos hepatócitos, inflamação, congestão e alterações nos parâmetros de ácidos graxos para a CAAF foram 33,3%, 80%, 0% e 0%, respectivamente, enquanto que as sensibilidades das mesmas variáveis para o método tru-cut foram 66,7%, 40%, 100% e 20%, respectivamente. DISCUSSÃO Ambas as técnicas foram superiores em alguns aspectos. A CAAF pode ser uma alternativa atraente à biópsia por tru-cut e aplicada como prática de rotina no diagnóstico de doenças hepáticas não tumorais.

Research advances in the pathogenesis of alcoholic liver disease / 临床肝胆病杂志

Alcoholic liver disease (ALD) is a common cause of liver dysfunction and death due to liver-related diseases, which brings great harm to human health and social development. Many factors are involved in the development and progression of ALD, such as oxidative stress, change in gut microbiota, genetic variation, autophagy inhibition, and microRNAs. This article summarizes the mechanism of action of these factors in ALD, in order to provide a basis for the treatment of ALD and the discovery of new drug targets.

Mechanism of action and clinical application of 17β-hydroxysteroid dehydrogenase 13 in alcohol-related liver diseases / 临床肝胆病杂志

As a new hepatocyte-specific lipid droplet-related protein, 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) is involved in hepatocyte lipid synthesis. Recent studies have shown that an insertion-deletion variant of the HSD17B13 gene is associated with a reduced risk of chronic liver diseases; however, the specific biological function of HSD17B13 and its involvement in the pathogenesis of liver diseases remain unclear. This article elaborates on the biological function of HSD17B13, its mechanism of action in alcohol-related liver, and the research advances in clinical application.

Effect of anti-liver fibrosis Chinese patent drugs in preventing renal hypofunction associated with alcoholic liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effect of anti-liver fibrosis Chinese patent drugs on renal hypofunction associated with alcoholic liver disease (ALD). MethodsA retrospective analysis was performed for 592 patients with ALD who were admitted to Beijing Ditan Hospital, Capital Medical University, from August 1, 2008 to March 1, 2016, and according to whether they were treated with Fuzheng Huayu capsules, Anluo Huaxian pills, or Fufang Biejia Ruangan tablets for ≥180 cumulative defined daily doses, they were divided into Chinese medicine group and control group. After propensity score matching at a ratio of 1∶1, two groups were obtained with 187 patients in each group. Related data were recorded, including medical history, drinking amount, routine blood test results, liver and renal function, coagulation, and abdominal imaging findings. The t-test was used for comparison of normally distributed continuous data between groups, and the 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; the Kaplan-Meier method was used to compare the cumulative incidence rate of renal hypofunction between two groups. ResultsThere were no significant differences between the two groups in age, drinking amount, proportion of patients with hypertension or diabetes, baseline aspartate aminotransferase, estimated glomerular filtration rate, uric acid, and prothrombin time, and the patients were followed up for 36 months (range 23-54 months). Uric acid (hazard ratio ［HR］=1.003, 95% confidence interval ［CI］: 1001-1.005, P=0.001), prothrombin time (HR=1.103, 95%CI: 1.034-1.177, P=0.003), and red cell volume distribution width (HR=1.024, 95%CI: 1.011-1.038, P＜0.001) were independent risk factors for renal hypofunction in patients with ALD, and anti-liver fibrosis Chinese patent drug was an independent protective factor against renal hypofunction (HR=0.170, 95%CI: 0.053-0552, P=0.003). The Chinese medicine group had a significantly lower incidence rate of renal hypofunction than the control group (166% vs 32.1%, χ2=10.263, P=0.001). The subgroup analysis of the patients in the Chinese medicine group showed that Chinese medicine treatment for ＞24 months had the best effect (HR=0.210, 95%CI: 0.084-0.525, P=0.001). Compared with the control group, the Chinese medicine group had a significantly longer time to the onset of renal hypofunction (36 months vs 24 months, Z=-2.652, P=0.008). ConclusionAnti-liver fibrosis Chinese patent drugs can reduce the incidence rate and delay the onset of renal hypofunction in patients with ALD.

Protective effect of bone marrow mesenchymal stem cells derived exosomes on alcohol-induced hepatic injury / 中华传染病杂志

Objective To evaluate therapeutic effects of bone marrow mesenchymal stem cells(MSC)derived exosomes on alcohol-induced liver injury.Methods Eighteen male C57BL/6 mice aged 6 to 8 week were randomly divided into control group,model group and exosomes group,with 6 mice in each group.The mice in the model group and the exosomes group were fed with Lieber-DeCarli ad libitum diet(Dyets Inc.)for 4 weeks,followed by gavage a bolus of ethanol at day 26,27 and 28.The mice in the control group matched the alcohol-derived calories with dextran-maltose.Meanwhile,the mice in exosomes group were injected with MSC-exosomes via the tail vein at day 14 and 26.After the experiment,serum levels of alanine aminotransferase(ALT)and aspartate aminotransaminase(AST)were detected,and the pathological changes of liver tissues were observed.The expressions of nuclear factor erythroid 2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),CD63,CD81,TSG101 and Cytochrome C were analyzed by Western blot,and mRNA levels of Nrf-2,HO-1,interleukin(IL)-10 and IL-17 were analyzed by real-time polymerase chain reaction(RT-PCR).The commercial kits were used to detect serum IL-10,IL-17 levels and liver tissue malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)oxidative stress indicators.The numbers of regulatory T cell(Treg)and help T(Th)17 cells in the liver were analyzed by flow cytometry.One-way analysis of variance was used for comparison between groups.Results MSC-exosomes expressed positive markers CD63,CD81 and TSG101,but did not express the negative markers Cytochrome C.The serum ALT and AST levels in model group were(87.3±25.1)U/L and(223.2±43.5)U/L,respectively,while those in exosomes group were(47.7±12.0)U/L and(128.2±33.6)U/L,respectively.The differences between the two groups were both statistically significant(F=12.818 and 12.226,respectively,both P<0.05).Compared with control group,the SOD activity and GSH level in the model group significantly decreased with statistically significant differences(F=4.245 and 24.074,respectively,both P <0.05).Lieber-DeCarli ethanol feeding significantly increased intrahepatic MDA level in the model mice,which was reversed by MSC-exosomes supplementation,and the difference was statistically significant(F=36.675,P <0.05).Compared with control group,the intrahepatic protein expressions of Nrf-2 and HO-1 in model group were significantly decreased,while the expressions in exosomes group were obviously increased.The differences were statistically significant(F=33.623 and 14.960,respectively,both P <0.05).The expression trends of Nrf-2 and HO-1 mRNA were the same as those of protein expressions(F=20.784 and 276.336,respectively,both P <0.05).The proportions of liver Treg/Th17 in the control group,model group and exosomes group were 4.3±0.9,0.4±0.2,and 3.4±0.5,respectively.The differences among groups were statistically significant(F=64.227,P <0.05).Compared with control group,the serum protein and intrahepatic gene expression of IL-17 in the model group were significantly increased,which were reversed by MSC-exosomes treatment.The differences were statistically significant(F=15.581 and 40.095,respectively,both P<0.05).Serum IL-10 protein levels and intrahepatic IL-10 gene expression were significantly decreased after Lieber-DeCarli ethanol feeding,which were lower than the exosomes group.The differences were statistically significant(F=98.268 and 153.743,respectively,both P <0.05).Conclusions MSC-exosomes transplantation may relieve alcohol-induced liver injury.The mechanism could involve reduction of oxidative stress in the liver via regulating Nrf-2/HO-1 and normalizing the balance of Treg and Th17 cells.