Dihydroartemisinin ameliorates the liver steatosis in metabolic associated fatty liver disease mice by attenuating the inflammation and oxidative stress and promoting autophagy

ABSTRACT Purpose: To explore the effect and potential mechanism of dihydroartemisinin (DHA) on metabolism-related fatty liver disease. Methods: A metabolic associated fatty liver disease (MAFLD) mice model was induced with continuous supplies of high-fat diet. DHA was intraperitoneally injected into mice. The weight of mice was monitored. The concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by an automatic biochemical analyzer. The liver tissues were stained by hematoxylin and eosin and oil red O. The level of inflammation, oxidative stress, and autophagy was assessed by reverse transcription polymerase chain reaction, biochemical examination, Western blot and transmission electron microscope assays. Results: DHA treatment reduced theMAFLD-enhanced the level of weight gain, the concentrations of TC, TG, LDL and malonaldehyde, while increasedthe MAFLD-decreased the concentrations of HDL and superoxide dismutase. DHA ameliorated the MAFLD-aggravated pathological changes and the number of lipid droplets. Low dose of DHA declined the MAFLD-induced the enhancement of the expression of inflammatory factor. DHA treatment increased the MAFLD-enhanced the level of autophagy related protein, while decreased the MAFLD-reduced the protein level of p62. The increased level of autophagy was confirmed by transmission electron microscope. Conclusions: DHA can improve liver steatosis in MAFLD mice by inhibiting inflammation and oxidative stress and promoting autophagy.

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.

Expression and significance of Golgi protein 73 in alcoholic cirrhosis / 中国基层医药

Objective@#To investigate the expression and significance of Golgi protein 73 (GP73) in alcoholic cirrhosis.@*Methods@#From March 2015 to August 2017, 163 patients with alcoholic liver disease in the No.541 General Hospital were selected, including 51 patients with alcoholic fatty liver, 62 patients with alcoholic hepatitis, 50 patients with alcoholic liver cirrhosis, and 70 healthy volunteers were selected as control group.The liver function and the level of GP73 were detected.@*Results@#The GP73 level in the alcoholic liver cirrhosis group was (210.16±40.11)ng/mL, which was higher than that of the control group[(46.24±12.24)ng/mL], alcoholic fatty liver group [(85.10±20.43)ng/mL] and alcoholic hepatitis group[(160.18±32.05)ng/mL] (t=15.822, 30.022, 23.212, all P<0.05). GP73 was positively correlated with Gamma glutamyl transferase (GGT) (r=0.563, P<0.05), negatively correlated with albumin (Alb) (r=-0.488, P<0.05), and had no correlation with alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) (P>0.05). After treatment, the GP73 levels of effective patients in the alcoholic fatty liver group, alcoholic hepatitis group and alcoholic liver cirrhosis group were (54.16±11.18)ng/mL, (104.11±28.46)ng/mL, (122.03±30.54)ng/mL, respectively, which were lower than that of the ineffective patients (t=-4.600, -5.081 and -4.100, all P<0.05).@*Conclusion@#The GP73 level is significantly elevated in alcoholic liver disease.In alcoholic cirrhosis, GP73 level is the highest, has a certain relationship with the liver function index GGT, Alb and the therapeutic effect.

Quantitative detection and clinical value of CD44 in patients with nonalcoholic fatty liver disease / 中华肝脏病杂志

Objective@#To quantitatively detect CD44 expression in patients with nonalcoholic fatty liver disease (NAFLD) for comparative analysis.@*Methods@#Patients with chronic liver diseases accompanied with or without NAFLD, including chronic hepatitis B, cirrhosis and hepatocellular carcinoma after chronic hepatitis B, and healthy blood donors as normal controls who admitted to the Affiliated Hospital of Nantong University from May to October 2018 were selected. The proportion of CD44 positive cells was analyzed by flow cytometry. CD44 level was quantified by an enzyme-linked immunosorbent assay, and the biochemical indicators such as serum aspartate aminotransferase, alanine aminotransferase activity, total cholesterol and triglyceride were routinely analyzed. The cancerous and adjacent cancerous tissues of patients accompanied with or without NAFLD were collected by self-matching method and analyzed by immunoblotting and histochemistry and compared by CD44 integrated optical density. Image-Pro Plus version 6.0, Image J, GraphPad Prism 5.0, Photoshop, Microsoft Excel and IBM SPSS statistics 23 were used to analyze and draw pictures. An independent sample t-test was used to compare the differences between groups.@*Results@#Patients accompanied with NAFLD had hepatocyte injury and dyslipidemia. NAFLD and chronic liver disease patients had significantly elevated serum CD44 levels than normal control group (P < 0.01). CD44 positive lymphocyte ratio was 78.19 % ± 16.33 % in NAFLD patients and 68.47% ± 20.91% in chronic hepatitis B group, which was higher than the control group (46.51% ± 20.52%). Chronic hepatitis B group with steatosis had significantly higher CD44 concentration (181.42 ± 49.36) ng/ml than chronic hepatitis B group (142.52 ± 53.87) ng/ml and normal control group (99.47 ± 15.23) ng/ml. CD44/GAPDH ratio in the liver cancer group (1.306 ± 0.614) was significantly higher than paracancerous group (0.477 ± 0.291) and the difference between the two groups was statistically significant (t = 3.451, P = 0.004). The integrated optical density of CD44 in the NAFLD-related liver cancer and paracancerous group were 25.721 ± 5.881 and 14.155 ± 4.001 and the difference between the groups was statistically significant (t = 14.544, P < 0.001). The pathological features of high expression of CD44 in patients with hepatocellular carcinoma were significantly correlated with HBV infection, tumor size, single/multi-center, and lymph node metastasis, degree of differentiation, TNM grade, Child-Pugh score, portal vein tumor thrombus and extrahepatic metastasis. HCC patients with NAFLD had significantly higher serum CD44 (234.62 ± 69.40) ng/ml than patients without NAFLD (186.49 ± 58.89) ng/ml (t = -3.191, P = 0.002), but there was no statistically significant difference in the clinicopathological characteristics between the high/low CD44 groups of HCC patients with NAFLD.@*Conclusion@#The results suggest that CD44 is abnormally activated and its mechanism may play an important role in the progression of NAFLD.

Study on the correlation between small intestinal dendritic cells and non-alcoholic fatty liver disease in mice / 中华肝脏病杂志

Objective@#To preliminary, explore the effect of small intestinal epithelial dendritic cells on the occurrence and development of nonalcoholic fatty liver disease in mice.@*Methods@#Thirty-two (half male and half female) 4-week-old C57BL/6 mice were randomly divided into two groups. The mice were fed with normal diet (SD group) and high-fat diet (HFD group). Eight mice (half male and half female) were randomly killed from each group over the 14 and 20-weeks feeding period to observe their body weight, liver and small-intestine wet weight. Alanine aminotransferase, aspartate aminotransferase, blood glucose, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglyceride were determined by eyeball blood samples. Pathological diagnosis and alcoholic fatty liver disease activity score were collected. The number of mice small intestinal dendritic cells was observed under a microscope. Statistical analysis was performed to compare two groups of independent samples with homogeneity test of variance, t test, and covariance analysis.@*Results@#The body weight, liver wet weight, serum alanine aminotransferase and aspartate aminotransferase of mice in HFD group were significantly higher than those of control group at 20 weeks (P < 0.05), and the serum high density lipoprotein of mice in HFD group was significantly higher than that of SD group at 14 weeks (P < 0.05). At 14th weeks, the liver tissue of mice in HFD group had early pathological manifestations of hepatitis (fatty degeneration, punctate necrosis and balloon-like degeneration). Of which 87.5% (7/8) of them were diagnosed as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while only a few mice in SD group had early pathological manifestations of hepatitis. At 20th weeks, all mice in HFD group were diagnosed with non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while none of the mice in SD group was diagnosed with non-alcoholic fatty liver disease. At both time points, the percentage of small intestinal dendritic cells in HFD group was significantly higher than that in SD group (14 weeks: 4.181 ± 4.314 vs. 15.099 ± 10.349; 20 weeks: 9.615 ± 8.267 vs. 32.839 ± 24.475, both P < 0.05). Statistical analysis combined with the alcoholic fatty liver disease activity score showed that there was no linear correlation between the two groups (regression coefficient was 20.196%).@*Conclusion@#The number and different staging of small intestinal dendritic cells in mice is associated with the occurrence and development of NAFLD.

Expression and significance of Golgi protein 73 in alcoholic cirrhosis / 中国基层医药

Objective To investigate the expression and significance of Golgi protein 73 (GP73) in alcoholic cirrhosis.Methods From March 2015 to August 2017,163 patients with alcoholic liver disease in the No.541 General Hospital were selected,including 51 patients with alcoholic fatty liver,62 patients with alcoholic hepatitis,50 patients with alcoholic liver cirrhosis,and 70 healthy volunteers were selected as control group.The liver function and the level of GP73 were detected.Results The GP73 level in the alcoholic liver cirrhosis group was (210.16 ± 40.11)ng/mL,which was higher than that of the control group [(46.24 ± 12.24) ng/mL],alcoholic fatty liver group [(85.10 ± 20.43) ng/mL] and alcoholic hepatitis group[(160.18 ± 32.05) ng/mL] (t =15.822,30.022,23.212,all P ＜ 0.05).GP73 was positively correlated with Gamma glutamyl transferase (GGT) (r =0.563,P ＜ 0.05),negatively correlated with albumin (Alb) (r =-0.488,P ＜ 0.05),and had no correlation with alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP) and total bilirubin (TBIL)(P ＞ 0.05).After treatment,the GP73 levels of effective patients in the alcoholic fatty liver group,alcoholic hepatitis group and alcoholic liver cirrhosis group were (54.16 ± 11.18)ng/mL,(104.11 ± 28.46)ng/mL,(122.03 ±30.54)ng/mL,respectively,which were lower than that of the ineffective patients (t =-4.600,-5.081 and -4.100,all P ＜ 0.05).Conclusion The GP73 level is significantly elevated in alcoholic liver disease.In alcoholic cirrhosis,GP73 level is the highest,has a certain relationship with the liver function index GGT,Alb and the therapeutic effect.

Effect of human liver-derived stem cells in prevention and treatment of alcoholic fatty liver disease in mice / 临床肝胆病杂志

ObjectiveTo investigate the effect of intraperitoneal transplantation of human liver-derived stem cells in the prevention and treatment of alcoholic fatty liver disease in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into blank control group (group N), model control group (group M), and stem cell transplantation group (group S). The mice in group N were fed a normal diet, and those in the other two groups were fed Lieber-DeCarli alcohol liquid diet; at the same time, the mice in group S were given intraperitoneal transplantation of human liver-derived stem cells twice a week. After six weeks of intervention, body weight and liver index were measured, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also measured. The levels of TG and non-esterified fatty acid (NEFA) in the liver were measured, and liver pathological examination and oil red O staining of the liver were performed. One-way ANOVA was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in the serum levels of ALT, AST, TG, TC, and HDL-C and the content of TG and NEFA in the liver between the three groups (F=66.94, 7.15, 8.02, 18.64, 386, 2314 and 3049, all P＜0.05), Compared with group N, group M showed significant increases in levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue (all P＜0.05). Group S had significantly lower levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue than group M (all P＜0.05). Liver HE staining and oil red O staining showed that group S had a significantly lower degree of liver steatosis than group M. ConclusionIntraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.

Effect of human liver-derived stem cells in prevention and treatment of alcoholic fatty liver disease in mice / 临床肝胆病杂志

ObjectiveTo investigate the effect of intraperitoneal transplantation of human liver-derived stem cells in the prevention and treatment of alcoholic fatty liver disease in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into blank control group (group N), model control group (group M), and stem cell transplantation group (group S). The mice in group N were fed a normal diet, and those in the other two groups were fed Lieber-DeCarli alcohol liquid diet; at the same time, the mice in group S were given intraperitoneal transplantation of human liver-derived stem cells twice a week. After six weeks of intervention, body weight and liver index were measured, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also measured. The levels of TG and non-esterified fatty acid (NEFA) in the liver were measured, and liver pathological examination and oil red O staining of the liver were performed. One-way ANOVA was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in the serum levels of ALT, AST, TG, TC, and HDL-C and the content of TG and NEFA in the liver between the three groups (F=66.94, 7.15, 8.02, 18.64, 386, 2314 and 3049, all P＜0.05), Compared with group N, group M showed significant increases in levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue (all P＜0.05). Group S had significantly lower levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue than group M (all P＜0.05). Liver HE staining and oil red O staining showed that group S had a significantly lower degree of liver steatosis than group M. ConclusionIntraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.

Predictive value of CT evaluation of fatty liver for the severity of acute pancreatitis / 中国医师进修杂志

Objective@#To investigate the predictive value of CT evaluation of fatty liver for the severity of acute pancreatitis(AP).@*Methods@#The clinical and imaging data of 325 patients with AP from January 2013 to December 2017 were retrospectively analyzed. The demographic characteristics, etiological types, AP severity classification, persistent organ failure and death were collected. According to the ratio of the CT value of the liver and spleen (CT valueratio), whether the patients had fatty liver and the severity of fatty liver were determined. The incidence of persistent organ failure and mortality in AP patients with or without fatty liver and between the different severity grades of fatty liver were compared. Univariate and multivariate Logistic regression analysis was used to assess the independent risk factors for persistent organ failure in AP.@*Results@#Among the 325 AP patients, 86 (26.5%) patients were in line with the CT diagnostic criteria for fatty liver and 239 (73.5%) patients did not meet the CT diagnostic criteria of fatty liver. The incidence of persistent organ failure in AP patients with fatty liver (CT valueratio<1.0) was significantly higher than that without fatty liver (CT valueratio=1.0):17.4%(15/86) vs. 7.5%(18/239), P<0.05. The rate of persistent organ failure in AP patients increased proportionally with the severity grades of fatty liver [7.5% in patients without fatty liver, 7.5%(18/239) in mild (0.7<CT valueratio<1.0), 18.5%(5/27) in moderate (0.5<CT valueratio ≤ 0.7), and 7/19 in severe (CT valueratio ≤ 0.5) fatty liver], P<0.05. Single factor analysis showed that sex, body mass index (BMI, ≥ 25 kg/m2), etiological type, combined fatty liver were associated with persistent organ failure in AP (P<0.05 or<0.01). Multiple factor Logistic regression analysis showed that the elderly (≥60 years old), high BMI (≥ 25 kg/m2) and combined fatty liver were independent risk factors for persistent organ failure in AP (P<0.05 or<0.01).@*Conclusions@#Assessment of fatty liver and its severity in AP patients by CT is valuable to predict the risk of persistent organ failure.

Advances in epidemiology and serum markers for the noninvasive diagnosis of nonalcoholic fatty liver disease / 中华肝脏病杂志

The global prevalence rate of nonalcoholic fatty liver disease (NAFLD) has increased year by year, and it has become the number one cause for chronic liver disease in China. In addition, the trend of NAFLD has become more pronounced and evident in female gender and younger age group. The long-term persistence of fatty liver disease may cause serious consequences. There are no accepted diagnostic criteria for diagnosing noninvasive diagnosis of NAFLD. Alpha-ketoglutarate is a newly discovered serological marker of high diagnostic value and considered the most valuable potential biomarker along with cytokeratine-18 (CK-18).

Effects of glycyrrhizin on alcoholic fatty liver cells incluced in vitro and its mechanism / 重庆医学

Objective To investigate the effects of glycyrrhizin on the cell model of alcoholic fatty liver(AFL) induced in vitro and its possible mechanism.Methods The in vitro induced AFL cells were divided into the control group,separating ethanol group,glycyrrhizin group and continuous induction group.The levels of intracellular triglyceride(TG) and leakage amounts of ALT and AST,cell cycle change and protein and mRNA expressions of PPAR-γ,SREBP-1 and SCAP were measured.Results Glycyrrhizin could obviously reduce the apoptosis occurrence;compared with the control group,the level of intracellular TG and the leakage amounts of ALT and AST,and the protein and mRNA expressions of PPAR-γ,SREBP-1 and SCAP were significantly decreased(P＜0.05).Conclusion Glycyrrhizin may alleviate the fat change of in vitro induced AFL cells by down-regulating expressions of PPAR-γ,SREBP-1 and SCAP.

Effect of compound glycyrrhizin on alcoholic fatty liver disease / 中国基层医药

Objective To observe the clinical effect of compound glycyrrhizin in the treatment of alcoholic fatty liver disease(AFLD).Methods 68 AFLD patients according to the different treatment methods were divided into two groups.34 cases in the control group received conventional therapy ,34 cases in the observation group were given compound glycyrrhizin based on the conventional treatment .The clinical effect of the two groups was compared . Results The total effective rate of the observation group was 91.18%,which was higher than 64.71% of the control group,the difference was statistically significant (χ2 =6.928,P <0.05).The TBIL,GGT,AST,ALT of the observation group were (6.39 ±1.15)μmol/L,(157.79 ±17.39)U/L,(37.49 ±2.61)U/L,(24.45 ±2.16)U/L,respectively, which of the control group were (26.14 ±2.79)μmol/L,(417.59 ±45.89)U/L,(97.28 ±11.39)U/L,(54.33 ± 4.05) U/L,respectively,the differences between the two groups after treatment were statistically significant ( t =41.392,33.482,32.361,41.171,all P <0.05).The incidence rate of adverse reactions of the observation group was 5.88%,which was lower than 26.47% of the control group (χ2 =4.250,P <0.05).Conclusion Compared with conventional treatment,compound glycyrrhizin in the treatment of AFLD can effectively improve the patients 'TBIL, GGT,AST,ALT index,improve the clinical efficacy.

Improvement effect of n-3 polyunsaturated fatty acid on rat nonalcoholic fatty liver disease / 重庆医学

Objective To investigate the improvement effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on rat nonalcoholic fatty liver disease(NAFLD) induced by high fat diet.Methods Thirty Wister male rats were divided into the control group,model group and n-3 PUFA group.The high fat feeding was adopted to establish NAFLD model.After 20 weeks of experiment,7 cases were extracted from each group for detecting serum and liver total cholesterol (TC) and triacylglyceride(TG);other 3 cases were performed the liver HE staining,the levels of MCP-1,iNOS,TNF-α mRNA protein were detected by using the Real time quantitative PCR(qPCR) and Western blot.Results The TC and TG levels in serum and livers of the model group were significantly higher than those in the control group(P＜0.01),but which were evidently decreased after adding n-3 PUFA(P＜0.05).The HE staining clearly observed the rat hepatic cells fatty degeneration in the model group,while polyunsaturated fatty acid had obvious improvement effect on it.The inflammatory molecule MCP-1,iNOS,TNF-α gene expression levels in the model group were significantly higher than those in the control group(P＜0.05),while the expression levels of MCP-1,iNOS and TNF-α in the n-3PUFA group were significantly decreased compared with the model group.Conclusion High fat feeding can cause the severe fatty degeneration in rat liver,but polyunsaturated fatty acid can play obvious improvement effect.

Improvement effect of n-3 polyunsaturated fatty acid on rat nonalcoholic fatty liver disease / 重庆医学

Objective To investigate the improvement effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on rat nonalcoholic fatty liver disease(NAFLD) induced by high fat diet.Methods Thirty Wister male rats were divided into the control group,model group and n-3 PUFA group.The high fat feeding was adopted to establish NAFLD model.After 20 weeks of experiment,7 cases were extracted from each group for detecting serum and liver total cholesterol (TC) and triacylglyceride(TG);other 3 cases were performed the liver HE staining,the levels of MCP-1,iNOS,TNF-α mRNA protein were detected by using the Real time quantitative PCR(qPCR) and Western blot.Results The TC and TG levels in serum and livers of the model group were significantly higher than those in the control group(P＜0.01),but which were evidently decreased after adding n-3 PUFA(P＜0.05).The HE staining clearly observed the rat hepatic cells fatty degeneration in the model group,while polyunsaturated fatty acid had obvious improvement effect on it.The inflammatory molecule MCP-1,iNOS,TNF-α gene expression levels in the model group were significantly higher than those in the control group(P＜0.05),while the expression levels of MCP-1,iNOS and TNF-α in the n-3PUFA group were significantly decreased compared with the model group.Conclusion High fat feeding can cause the severe fatty degeneration in rat liver,but polyunsaturated fatty acid can play obvious improvement effect.

The role of cytochrome P450 in nonalcoholic fatty liver induced by high-fat diet: a gene expression profile analysis / 中华肝脏病杂志

Objective@#To clarify the role of cytochrome P450 in nonalcoholic fatty liver disease (NAFLD) by RNA-Seq and bioinformatics analysis.@*Methods@#A total of 20 male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60% kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end of the experiment, the body weight, liver weight, and hepatic triglyceride (TG) content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed for the liver tissues. The differentially expressed genes were screened out and subjected to bioinformatics analysis, including KEGG and GO BP enrichment analyses and interaction network analysis. Comparison of means between the two groups was made using t-test.@*Results@#Compared with the control group, the mice in the model group were obviously obese, with significantly increased body weight (41.41 ± 6.01 g vs 28.78 ± 1.79 g, t = 6.04, P < 0.01) and liver weight (1.38 ± 0.30 g vs 1.08 ± 0.10 g, t = 2.89, P < 0.01). The mice in the model group showed obvious steatosis, accompanied by a small amount of inflammatory cell infiltration, but with no obvious fibrosis, according to the results of HE staining. In addition, the hepatic TG content in the model group was significantly increased compared with that in the control group (0.64 ± 0.01 mg/mg vs 0.29 ± 0.06 mg/mg, t = 10.11, P = 0.04). Compared with the control group, a total of 367 differentially expressed genes, including 211 down-regulated and 156 up-regulated ones, were identified in the model group according to the RNA-seq results. Meanwhile, 19 CYP450 subtypes, accounting for 5% of the differentially expressed genes, were identified, and CYP2E1, CYP2C70, CYP3A11, CYP3A25, CYP2D26, CYP4A10, CYP17A1, CYP2B10, and CYP2C38 were involved in oxidative stress, steroid hormone metabolism, fatty acid metabolism, arachidonic acid metabolism, and the PPAR signaling pathway. An interaction network was constructed with 30 nodes, and CYP2E1 and CYP2C70 were identified as key nodes. RT-PCR validation results showed that the expression changes of CYP450 subtypes and lipid metabolism-related genes were consistent with the findings of sequencing.@*Conclusion@#The CYP450 family plays a vital role in the pathogenesis of fatty liver by regulating lipid metabolism-related pathways, including oxidative stress, arachidonic acid metabolism, steroid hormone metabolism , and fatty acid metabolism.

Relationship between alcoholic fatty liver disease and carotid intima-media thickness and influencing factors for carotid intima-media thickness / 临床肝胆病杂志

ObjectiveTo assess the relationship between alcoholic fatty liver disease (AFLD) and carotid intima-media thickness (CIMT) and the influencing factors for CIMT. MethodsA cross-sectional study was conducted in 147 males who were inpatients or had physical examination at the Taishan Hospital in Shandong Province during January 2012 to December 2013. The participants, including 136 drinking cases and 11 non-drinking cases, were divided into mild AFLD group (A, 45 cases), moderate to severe AFLD group (B, 58 cases), and non-AFLD group (C, 44 cases). Comparison of mean values between groups was performed using one-way ANOVA, and pairwise comparisons were performed using the LSD test (for homogeneity of variance) or Tamhane's test (for heterogeneity of variance). Results(1) CIMT was significantly higher in group B than in group C (P=0.001). (2) BMI was significantly higher in group A than in group C (P=0.029). Total cholesterol, triglyceride, very-low-density lipoprotein, apolipoprotein B, and uric acid levels significantly rose in groups A and B compared with group C (P＜0.05). (3) Gamma-glutamyl transpeptidase (GGT) level was significantly higher in group A than in group C (P=0001), whereas alanine transaminase, aspartate aminotransferase, and GGT levels were significantly higher in group B than in group C (P=0.023, 0.003, and 0.000, respectively). (4) Serum creatinine level was significantly lower in groups A and B than in group C (P=0007 and 0.005, respectively). ConclusionAFLD can cause the increase in CIMT, resulting in metabolic syndrome-like changes and liver/kidney dysfunction. With increasing severity of AFLD, CIMT increase becomes more significant. Thus, AFLD can be used as an indicator for predicting CIMT increase in human population.

Hepatitis alcohólica severa no respondedor a a glucocorticoides: reporte de un caso / Alcoholic hepatitis not responding to corticosteroids: a case report

INTRODUCCIÓN: La hepatitis alcohólica corresponde a un daño inflamatorio agudo sobre un hígado progresivamente dañado por la ingesta excesiva y prolongada de alcohol. Puede presentar ictericia, manifestaciones de alcoholismo crónico e insuficiencia hepática progresiva. PRESENTACIÓN DEL CASO: Varón de 60años con antecedentes de daño hepático crónico secundario a alcoholismo activo, que presentó cuadro de dos semanas de ictericia progresiva, prurito y bradipsiquia, asociado a leucocitosis, hiperbilirrubinemia, y elevación discreta de transaminasas, con predominio de GOT sobre GPT. Hemocultivos, urocultivo y serologías para virus hepatotropos fueron negativos. La ecografía abdominal mostró signos de hepatopatía crónica, sin dilatación de vía biliar. Con una función discriminante de Maddrey de 106 puntos se inició pentoxifilina, evolucionando tórpidamente. Se agregó prednisona durante siete días; se obtiene una puntuación de Lille de 0,99 (no respondedor), suspendiendo los corticoides. Progresó la insuficiencia hepática, con posterior insuficiencia renal aguda, acidosis metabólica, trastornos hidroelectrolíticos y fallecimiento al mes de evolución. DISCUSIÓN: La hepatitis alcohólica posee alta mortalidad. Existen múltiples escalas pronósticas. Los corticoides están indicados en casos severos, sin embargo hasta un 40 por ciento se catalogan como no respondedores. Se requieren nuevos tratamientos para mejorar la supervivencia de estos pacientes.

INTRODUCTION: Alcoholic hepatitis constitutes an acute inflammatory episode due to prolonged alcohol abuse on a previously damaged liver. Clinical features include jaundice, signs of chronic alcoholism and progressive liver failure. CASE REPORT: A 60-yearold male with a history of cirrhosis due to ongoing excessive intake of alcohol presented a two week history of progressive jaundice, pruritus, and bradypsychia. Laboratory tests showed leukocytosis, hyperbilirubinemia and a mild elevation of liver enzymes (GOT over GPT). Blood and urine cultures as well as serological markers for viral hepatitis were negative. Abdominal ultrasound showed signs of chronic liver disease, with no bile duct dilatation. A modified Maddrey’s discriminant function of 106 was determinant on starting therapy with pentoxifyline. However, patient’s status deteriorated. Prednisone was added to the treatment but seven days later, the patient was categorized as a non-responder (Lille score of 0.99), so the glucocorticoids were suspended. The patient’s liver failure progressed, after which renal failure, metabolic acidosis and electrolytic abnormalities developed; that led to his death after one month from admission. DISCUSSION: Alcoholic hepatitis requires prompt diagnosis and treatment, due to its high death rate. There are various prognostic scales available, one of which is the modified Maddrey’s discriminant function. The fundamental therapeutic measure is the use of intravenous glucocorticoids; yet up to 40 percent of patients qualify as non-responders.

Effect of Hovenia Dulcis Thunb liquid on the expression of UCP2 gene in ethanol-induced superfatted L-02 cells in vitro / 中国医师杂志

Objective To establish the model of alcohol-induced hepatocyte steatosis in L-02 liver cells in vitro,investigate the relationship between cell damage,UCP2 gene expression and ethanol concentrations in L-02 cells of steatosis,and explore the protective effect of Hovenia Dulcis Thunb extracted liquid.Method Hovenia Dulcis Thunb extracted liquid at the most compatible dosage was applied to the L-02 cells of steatosis.Then UCP2 mRNA was detected by the semi-quantitative RT-PCR method.Results In steatosis model groups,UCP2 mRNA expression was downregulated ( P ＜0.05).In the steatosis groups treated with Hovenia Dulcis Thunb extracted liquid,UCP2 mRNA level was significantly increased compared to steatosis group ( its expression level increased from 0.4859 to 0.7442 after treatment of 0.6％ ethanol,P＜ 0.05).Conclusions Ethanol can down-regulate the UCP2 mRNA expression of L-02 cells in a certain period.The low expression of UCP2 mRNA is probably relevant to the occurrence of alcoholic fatty liver disease.Hovenia Dulcis Thunb can prevent from the cell toxicity of ethanol and decrease the degree of steatosis.Hovenia Dulcis Thunb extracted liquid can increase the expression level of UCP2 mRNA in the L-02 cells.

Correlation of nonalcoholic fatty liver disease with urinary albumin excretion ratio in type 2 diabetes mellitus / 中国医师进修杂志

Objective To observe the relationship of liver ultrasound class and urinary albumin excretion ratio (UAER) in type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD). Methods One hundred and ninety-seven T2DM patients were divided into 3 groups according to the degree of hepar adiposum: group A (66 subjects without NAFLD), group B (63 subjects with mild NAFLD) and group C (68 subjects with moderate or severe NAFLD). Their clinical indexes,UAER and biochemical parameters were measured and compared, the relative analysis of blood fat, HOMA-IR and UAER was done. Results Compared with those in group A, the levels of UAER were significantly increased [(86.49 ± 65.19) mg/24 h vs. (115.16 ± 101.99) mg/24 h vs. (159.45 ± 149.08) mg/24 h,P ＜ 0.05], and the levels of high density lipoprotein cholesterol decreased in group B and group C[(1.21 ± 0.37) mmol/L vs.(1.05 ± 0.38) mmol/L vs. (0.99 ± 0.21) mmol/L,P ＜ 0.05]. Multiple stepwise regression analysis showed that triglyeride was the most important risk factor affecting UAER(P ＜ 0.05). Conclusions There is a close relationship between NAFLD and UAER in T2DM. In the subjects with moderate or severe NAFLD, the UAER increases which indicates that these patients already have capillary vessel injury apparently.

Combination of taurine with silybin meglumine in treatment of patients with non-alcohlic steatohepatitis / 中华消化杂志

Objective To evaluate the therapeutic effects of taurine combined with silybin meglumine in patients with non-alcoholic steatohepatitis (NASH). Methods One hundred patients with NASH were divided into two groups with 50 for each. The patients in the control group received polyene phosphatidyl choline (456 mg) combined with silybin meglumine (100 mg) 3 times daily for 24 weeks. While those in the treatment group received taurine (2 g) combined with silybin meglumine (100 mg) 3 times daily for 24 weeks. All patients were asked to take up basic therapy including drinking without alcohol, restricting sugary and fatty intake, improving food structure, carrying moderate aerobics and lightening body weight. Results At the end of 24 weeks, the clinical symptoms and the liver function ameliorated in two groups. Ultrasonic or CT examination showed that the steatohepatitits was improved significantly in two groups. Additionally, the levels of blood glucose, serum triglyceride and cholesterol as well as BMI decreased simultaneously (all P value <0. 05). Whereas the treatment group was superior to control group in aspect of amelioration of inappetite, nausea and vomiting as well as lever of serum triglyceride (all P value <0. 05). There was no side effect in the treatment group. Conclusion Based on the basic therapy, taurine combined with silybin meglumine can mitigate the degree of NASH, improve the metabolism of blood glucose and lipid with few side-effects.