Effect of Dendrobium officinale leaf fermentation fluid on a mouse model of alcoholic hepatitis and its mechanism of action / 临床肝胆病杂志

ObjectiveTo investigate the intervention mechanism of Dendrobium officinale leaf fermentation fluid in mice with alcoholic hepatitis. MethodsA total of 70 healthy male C57BL/6J mice， aged 6-8 weeks， were randomly divided into normal group， model group， liquid feed control group， silybin group， and low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups， with 10 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given Lieber-DeCarli classic liquid diet for 8 weeks to induce alcoholic hepatitis. During modeling， the mice in the low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups were given Dendrobium liquid manufactured by Warmen Pharmaceutical， and the mice in all the other groups were given pure water； the mice in the normal group， the model group， and the liquid feed control group were given normal saline by gavage， those in the silybin group were given silybin 0.25 mL/10 g by gavage， and those in the low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups were given Dendrobium officinale leaf fermentation fluid at a dose of 0.125 mL/10 g， 0.250 mL/10 g， and 0.375 mL/10 g， respectively， by gavage， once a day. At week 8， chloral hydrate was injected intraperitoneally for anesthesia， and blood samples were collected from the eyeball. After serum was separated， the biochemical method was used to measure the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； HE staining and oil red staining were used to observe liver histopathology and lipid accumulation in mice； multiplex Luminex assay was used to measure the serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and CCL2； quantitative real-time PCR， Western blot， and immunofluorescence assay were used to measure the protein expression levels of NLRP3， caspase-1， caspase-11， gasdermin D （GSDMD）， N-terminal gasdermin D （GSDMD-N） 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. ResultsCompared with the normal group， the model group had significant increases in the serum levels of AST， ALT， IL-6， IL-1β， TNF-α， and CCL2 （all P<0.05）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the serum levels of AST， ALT， IL-6， IL-1β， TNF-α， and CCL2 （all P<0.05）. HE staining showed that the model group had disordered structure of hepatic lobules， with a large number of steatosis vacuoles and massive cell necrosis， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had alleviation of liver histopathological injury， intact structure of most hepatic lobules， and a small amount of inflammatory cell infiltration. Oil red staining showed that the model group had accumulation of large and small lipid droplets in the liver and a significant increase in liver fat content， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant alleviation of hepatic steatosis， with the presence of sporadic small lipid droplets. Immunofluorescence assay of liver tissue showed that compared with the normal group， the model group had a significant increase in the ratio of GSDMD-positive staining area in hepatocyte cytoplasm （P<0.001）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had a significant reduction in such ratio in hepatocyte cytoplasm （P<0.001）. Quantitative real-time PCR showed that compared with the normal group， the model group had significant increases in the protein expression levels of NLRP3， caspase-1， caspase-11， GSDMD， GSDMD-N， interleukin-18 （IL-18）， and IL-1β in liver tissue （all P<0.05）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the protein expression levels of NLRP3， caspase-1， caspase-11， GSDMD， GSDMD-N， IL-18， and IL-1 （all P<0.05）. Compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the protein expression levels of caspase-1 and caspase-11 （both P<0.05）， with a relative expression level of caspase-1 of 1.757 （reduced by 26.6% compared with the model group） and a relative expression level of caspase-11 of 0.455 （reduced by 70.3% compared with the model group）， suggesting that caspase-11 showed a greater reduction than caspase-1. ConclusionDendrobium officinale leaf fermentation fluid can alleviate alcoholic hepatitis in mice， possibly by inhibiting the non-classical cell pyroptosis pathway mediated by caspase-11.

Ethanol promoting the upregulation of C-X-C Motif Chemokine Ligand 1（CXCL1） and C-X-C Motif Chemokine Ligand 6（CXCL6） in models of early alcoholic liver disease.

Alcoholic liver disease (ALD) denotes a series of liver diseases caused by ethanol. Recently, immune-related genes (IRGs) play increasingly crucial role in diseases. However, it's unclear the role of IRGs in ALD. Bioinformatic analysis was used to discern the core immune-related differential genes (IRDGs) in the present study. Subsequently, Cell Counting Kit-8 say, oil red O staining, and triglyceride detection were employed to explore optimal experimental conditions of establishing hepatocellular models of early ALD. Ultimately, real-time reverse transcription-PCR and immunohistochemistry/immunocytochemistry methods were adopted to verify the expressions of mRNA and proteins of core IRDGs, respectively. C-X-C Motif Chemokine Ligand 1 (Cxcl1) and Cxcl6 were regarded as core IRDGs via integrated bioinformatics analysis. Besides, Lieber Decarli Ethanol feeding and 200 mM and 300 mM ethanol stimulating L02 cells for 36 h can both successfully hepatocellular model. In ethanol groups, the levels of CXCL1 and CXCL6 mRNA were significantly upregulated than pair-fed groups (P < 0.0001). Also, immunohistochemistry revealed that positive particles of CXCL1 and CXCL6 in mice model of early ALD were obviously more than control groups (P < 0.0001). Besides, in L02 hepatocytes stimulated by ethanol, CXCL1 and CXCL6 mRNA were over-expressed, compared with normal L02 cells (P < 0.0001). Meanwhile, immunocytochemistry indicated that CXCL1 and CXCL6 proteins in hepatocellular model of early ALD were higher than normal L02 hepatocytes stimulus (P < 0.0001). Ethanol promoted the upregulation of Cxcl1 and Cxcl6 mRNA and proteins in models of early ALD, denoting their potentiality of acting as biomarkers of ALD.

Evaluation and influencing factors of the short-term prognosis of severe alcoholic hepatitis with different underlying liver diseases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with severe alcoholic hepatitis (AH) with different underlying liver diseases and the influencing factors for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 170 patients with severe AH who were admitted to Tianjin Third Central Hospital from August 2004 to August 2018, and according to the underlying liver disease, they were divided into group A (27 patients without liver cirrhosis), group B (52 patients with compensated liver cirrhosis), and group C (91 patients with decompensated liver cirrhosis). Related scores were calculated, including Maddrey’s discriminant function (MDF) score, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, Model for End-Stage Liver Disease (MELD) score, age-bilirubin-international normalized ratio-creatinine (ABIC) score, and Glasgow alcoholic hepatitis score (GAHS). An analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. Univariate and multivariate Cox regression analyses were used to screen out the independent influencing factors for the short-term prognosis of patients with severe AH. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate between groups. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUC) and 95% confidence interval (CI), sensitivity, and specificity for each predictive model, and the DeLong method was used for comparison. ResultsThe 28-day survival rates of patients in groups A, B, and C were 88.9%, 80.8%, and 51.6%, respectively, with a significant difference between the three groups (χ2=1983, P＜0.001). The AUCs (95% CIs) of MELD score, MDF score, GAHS score, ABIC score, and CLIF-SOFA score were 0.584 (0.493-0.676), 0.696 (0.605-0.786), 0.644 (0.554-0.735), 0.745 (0.662-0.827), and 0.795 (0.726-0.863), respectively, in predicting 28-day mortality rate, and there were significant differences between CLIF-SOFA score and MDF, MELD, and GAHS scores (all P＜0.05); CLIF-SOFA score had a sensitivity of 79.0% and a specificity of 67.9% at the optimal cut-off value of 850 points in predicting 28-day mortality rate. Different underlying liver diseases (hazard ratio ［HR］=2.296, 95% CI: 1.356-3887, P=0.002) and hepatic encephalopathy (HR=1.911, 95% CI: 1.059-3.449, P=0.031) at disease onset were risk factors for 28-day prognosis. ConclusionPatients with severe AH with different underlying liver diseases have different clinical features and short-term prognoses. Different underlying liver diseases and hepatic encephalopathy at disease onset are closely associated with the 28-day prognosis of patients with severe AH. CLIF-SOFA score can predict the 28-day prognosis of patients with severe AH.

Predictors of steroid non-response and new approaches in severe alcoholic hepatitis.

Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.

Prognostic Value of the Alcoholic Hepatitis Histologic Score in Korean Patients with Biopsy-Proven Alcoholic Hepatitis.

Background/Aims: The alcoholic hepatitis histologic score (AHHS) is a recently developed clinical model for predicting short-term mortality in Caucasian patients with alcoholic hepatitis (AH). The AHHS has not been extensively validated in other ethnic populations. This study validated the AHHS in a Korean patient cohort. Methods: We conducted a prospective cohort study of hospitalized Korean patients with AH between January 2010 and August 2017. Histopathological findings were assessed to determine the AHHS in all study subjects. Histopathological risk factors were examined by Cox regression analysis to predict overall survival (OS). Kaplan-Meier curves were plotted to assess the diagnostic performance of the AHHS. Results: We recruited a total of 107 patients with biopsy-proven AH. None of the individual AHHS components were associated with 3-month mortality. However, the bilirubinostasis type and fibrosis severity were significantly associated with AH mortality beyond 6 months (all p<0.05, except fibrosis severity for 6-month mortality) and OS (all p<0.05). The modified AHHS classification as a binary variable (<5 vs ≥5) was also associated with OS (hazard ratio, 2.88; 95% confidence interval [CI], 1.50 to 5.56; p=0.002), and had higher predictive performance for OS (concordance index [C-index], 0.634; 95% CI, 0.561 to 0.707) than the original AHHS classification (mild vs moderate vs severe: C-index, 0.577; 95% CI, 0.498 to 0.656). This difference was statistically significant (p=0.045). Conclusions: In this prospective Korean AH cohort, the modified AHHS was significantly associated with OS. Therefore, the AHHS might be a useful histological prognosticator for long-term prognosis in patients with nonsevere AH.

Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve short-term survival but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation. T cells are implicated in AH and steroid responsiveness. We measured ;ex vivo T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients (bilirubin >80 µmol/L and ratio of aspartate aminotransferase to alanine aminotransferase >1.5 who were heavy alcohol consumers with discriminant function [DF] ≥32), were recruited from University Hospitals Plymouth NHS Trust. T cells were obtained and stimulated ;ex vivo. Cytokine expression levels were determined by flow cytometry and protein multiplex analysis. Twenty-three patients were recruited (10 male; median age 51 years; baseline DF 67; 30% 90-day mortality). Compared to T cells from nonsurvivors at day 90, T cells from survivors had higher baseline baseline intracellular interleukin (IL)-10:IL-17A ratio (0.43 vs 1.20, p=0.02). Multiplex protein analysis identified interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α) as independent predictors of 90-day mortality (p=0.04, p=0.01, respectively). The ratio of IFNγ to TNF-α was predictive of 90-day mortality (1.4 vs 0.2, p=0.03). These data demonstrate the potential utility of T cell cytokine release assays performed on pretreatment blood samples as biomarkers of survival in patients with severe AH. Our key findings were that intracellular IL-10:IL-17A and IFNγ:TNF-α in culture supernatants were predictors of 90-day mortality. This offers the promise of developing T cell-based diagnostic tools for risk stratification.

Application of bacteriophage technique in the treatment of alcoholic liver disease / 临床肝胆病杂志

Alcoholic hepatitis (AH) is a severe alcohol-associated liver disease with a mortality rate as high as 40%. A recent study reveals that the exotoxin (cytolysin)-secreting gut bacterium Enterococcus faecalis is a critical factor for AH, which can be eliminated by bacteriophages, and therefore, the use of bacteriophages for the treatment of AH provide a new treatment option for AH. This article introduces this pioneering study and the knowledge of bacteriophages and cytolysin, so as to provide a theoretical basis for the clinical research on AH.

What's new in alcoholic hepatitis / 临床肝胆病杂志

@#Alcoholic hepatitis is an important type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use.In the present article,the pathogenesis,clinical characteristics,diagnosis,current therapies aud future treatment strategies of alcoholic hepatitis are summarized and reviewed in order to help the hepatologists to better understand this kind of disease in clinical practice.

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.

A bioinformatics analysis of the microRNA-mRNA differential expression network for alcoholic hepatitis / 临床肝胆病杂志

ObjectiveTo establish a microRNA-mRNA differential expression network for alcoholic hepatitis (AH), and to investigate new targets for the diagnosis and treatment of AH. MethodsDifferentially expressed microRNAs and mRNAs between AH patients and normal controls were screened out. Related software including TargetScan, DIANA, MIRDB, PICTAR, and miRWalk 2.0 was used to search for the target genes of differentially expressed microRNA, and a key microRNA-mRNA network was established using the differentially expressed mRNAs that changed in an opposite way to microRNA. The Database for Annotation, Visualization and Integrated Discovery was used for the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of target genes. The GCBI online software (www.gcbi.com.cn) was used for enrichment analysis of target genes and core network establishment. The GeneMANIA database in Cytoscape software (genemania.org) was used to perform a protein-protein interaction analysis of key target genes. The above three methods were compared in terms of the search for key pathways involved in the development of AH. ResultsA key microRNA-mRNA network was established with 5 differentially expressed microRNAs including hsa-mir-21-5p, hsa-mir-148a-3p, and hsa-mir-30e-5p and 51 target genes including collagen type IV alpha 1 chain (COL4A1), thrombospondin-2 (THBS2), and integrin alpha 6 (IGTA6). A protein-protein interaction network of key target genes was established. The GO analysis and various pathway analyses showed that the PI3K-Akt pathway and local adhesion were closely associated with AH. ConclusionDuring the development of AH, there are complex interactions between the related proteins of key target genes. COL4A1 and THBS2 may promote the development of AH by activating ITGA6 to regulate the PI3K-Akt pathway and the process of local adhesion. The establishment of the microRNA-mRNA network reveals the key links in the development of AH and highlights the focus of research. The discovery of the genes associated with the PI3K-Akt pathway in AH is expected to provide new targets for the diagnosis and treatment of AH.

Severe alcoholic hepatitis and acute-on-chronic liver failure / 临床肝胆病杂志

Rapid progression or aggravation of jaundice, coagulation abnormalities and liver-related complications in patients with alcoholic hepatitis indicates that they may develop severe alcoholic hepatitis. Some of these patients can progress acute-on-chronic liver failure with acute insults, such as infection and binge drinking and binge, showing as acute decompensation, organ failure and high 28-day mortality rate. Early identification and effective intervention can improve the prognosis of acute-on-chronic liver failure. Intestinal barrier dysfunction and liver-gut axis imbalance play an important role in the development of severe alcoholic hepatitis and acute-on-chronic liver failure. It is important to improve the basic nutritional status of patients. Effective drug therapies are limited in improving the condition and prognosis of acute-on-chronic liver failure. Early liver transplantation can bring great benefits to these patients.

Clinical diagnosis of alcoholic hepatitis / 临床肝胆病杂志

Based on the significant differences in definition, clinical features, and prognosis between alcoholic hepatitis (AH) and severe AH, it is recommended to classify AH into mild and severe AH. As for the disease spectrum of hospitalized patients with alcoholic liver disease, most patients have liver cirrhosis, and about 15% have mild or severe AH. Alcoholic liver failure belongs to the category of severe AH. Severe AH is a clinical diagnosis, while alcoholic steatohepatitis is a pathological diagnosis. The clinical diagnostic criteria for severe AH tend to be consistent in European and the United States of America, but the Chinese guideline released in 2018 is not consistent with the guidelines from western countries.

Importance of the clinical research on alcoholic hepatitis / 临床肝胆病杂志

Alcoholic hepatitis (AH) is a non-infectious inflammatory injury of the liver and often occurs on the basis of chronic liver disease including fatty liver disease and liver cirrhosis. Acute exacerbation of liver disease due to heavy drinking within a short period of time is a severe manifestation of AH. The prognosis of AH depends on treatment timing and methods, and liver function can quickly recover or rapidly deteriorate into multiple organ failure. Many clinicians lack the experience in early identification and timely treatment of AH, due to a lack of typical clinical manifestations and specific auxiliary examinations, which affects clinical treatment, delays treatment, and exposes some AH patients to the risk of death. Therefore, it is imperative to conduct more clinical studies on AH, summarize real-world data, and develop expert consensus.

A bioinformatics analysis of the microRNA-mRNA differential expression network for alcoholic hepatitis / 临床肝胆病杂志

ObjectiveTo establish a microRNA-mRNA differential expression network for alcoholic hepatitis (AH), and to investigate new targets for the diagnosis and treatment of AH. MethodsDifferentially expressed microRNAs and mRNAs between AH patients and normal controls were screened out. Related software including TargetScan, DIANA, MIRDB, PICTAR, and miRWalk 2.0 was used to search for the target genes of differentially expressed microRNA, and a key microRNA-mRNA network was established using the differentially expressed mRNAs that changed in an opposite way to microRNA. The Database for Annotation, Visualization and Integrated Discovery was used for the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of target genes. The GCBI online software (www.gcbi.com.cn) was used for enrichment analysis of target genes and core network establishment. The GeneMANIA database in Cytoscape software (genemania.org) was used to perform a protein-protein interaction analysis of key target genes. The above three methods were compared in terms of the search for key pathways involved in the development of AH. ResultsA key microRNA-mRNA network was established with 5 differentially expressed microRNAs including hsa-mir-21-5p, hsa-mir-148a-3p, and hsa-mir-30e-5p and 51 target genes including collagen type IV alpha 1 chain (COL4A1), thrombospondin-2 (THBS2), and integrin alpha 6 (IGTA6). A protein-protein interaction network of key target genes was established. The GO analysis and various pathway analyses showed that the PI3K-Akt pathway and local adhesion were closely associated with AH. ConclusionDuring the development of AH, there are complex interactions between the related proteins of key target genes. COL4A1 and THBS2 may promote the development of AH by activating ITGA6 to regulate the PI3K-Akt pathway and the process of local adhesion. The establishment of the microRNA-mRNA network reveals the key links in the development of AH and highlights the focus of research. The discovery of the genes associated with the PI3K-Akt pathway in AH is expected to provide new targets for the diagnosis and treatment of AH.

Severe alcoholic hepatitis and acute-on-chronic liver failure / 临床肝胆病杂志

Rapid progression or aggravation of jaundice, coagulation abnormalities and liver-related complications in patients with alcoholic hepatitis indicates that they may develop severe alcoholic hepatitis. Some of these patients can progress acute-on-chronic liver failure with acute insults, such as infection and binge drinking and binge, showing as acute decompensation, organ failure and high 28-day mortality rate. Early identification and effective intervention can improve the prognosis of acute-on-chronic liver failure. Intestinal barrier dysfunction and liver-gut axis imbalance play an important role in the development of severe alcoholic hepatitis and acute-on-chronic liver failure. It is important to improve the basic nutritional status of patients. Effective drug therapies are limited in improving the condition and prognosis of acute-on-chronic liver failure. Early liver transplantation can bring great benefits to these patients.

Clinical diagnosis of alcoholic hepatitis / 临床肝胆病杂志

Based on the significant differences in definition, clinical features, and prognosis between alcoholic hepatitis (AH) and severe AH, it is recommended to classify AH into mild and severe AH. As for the disease spectrum of hospitalized patients with alcoholic liver disease, most patients have liver cirrhosis, and about 15% have mild or severe AH. Alcoholic liver failure belongs to the category of severe AH. Severe AH is a clinical diagnosis, while alcoholic steatohepatitis is a pathological diagnosis. The clinical diagnostic criteria for severe AH tend to be consistent in European and the United States of America, but the Chinese guideline released in 2018 is not consistent with the guidelines from western countries.

Importance of the clinical research on alcoholic hepatitis / 临床肝胆病杂志

Alcoholic hepatitis (AH) is a non-infectious inflammatory injury of the liver and often occurs on the basis of chronic liver disease including fatty liver disease and liver cirrhosis. Acute exacerbation of liver disease due to heavy drinking within a short period of time is a severe manifestation of AH. The prognosis of AH depends on treatment timing and methods, and liver function can quickly recover or rapidly deteriorate into multiple organ failure. Many clinicians lack the experience in early identification and timely treatment of AH, due to a lack of typical clinical manifestations and specific auxiliary examinations, which affects clinical treatment, delays treatment, and exposes some AH patients to the risk of death. Therefore, it is imperative to conduct more clinical studies on AH, summarize real-world data, and develop expert consensus.

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.

Measuring Intrahepatic Vascular Changes Using Contrast-Enhanced Ultrasonography to Predict the Prognosis of Alcoholic Hepatitis Combined with Cirrhosis: A Prospective Pilot Study.

Background/Aims: Acute hepatic dysfunction combined with alcoholic hepatitis (AH) in alcoholic cirrhosis is related to hepatic hypo-perfusion secondary to intrahepatic necroinflammation, neoangiogenesis, and shunt. The hepatic vein arrival time (HVAT) assessed by microbubble contrast-enhanced ultrasonography (CEUS) is closely correlated with the severity of intrahepatic changes. We investigated the usefulness of HVAT to predict short-term mortality of AH in cirrhosis. Methods: Thirty-nine patients with alcoholic cirrhosis (27 males) and AH were prospectively enrolled. HVAT study was performed within 3 days after admission using ultrasonic contrast (SonoVue®). The primary outcome was 12-week mortality. Results: Twelve-week mortality developed in nine patients. HVAT was significantly different between the mortality and survival groups (9.3±2.0 seconds vs 12.6±3.5 seconds, p=0.002). The odds ratio of a shortened HVAT for 12-week mortality was 1.481 (95% confidence interval, 1.050-2.090; p=0.025). The area under the receiver operating characteristic curve of HVAT for 12-week mortality was 0.787 (p=0.010). The combination of MDF and HVAT ≥11.0 seconds resulted in an 87.5% survival rate even if the MDF score ≥32; however, HVAT ＜11.0 seconds was related with mortality despite a MDF score＜32. Conclusions: HVAT using microbubble CEUS could be a useful additional index to predict short-term mortality in patients with AH and cirrhosis.