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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=1983, 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 850 points in predicting 28-day mortality rate. Different underlying liver diseases (hazard ratio ［HR］=2.296, 95% CI: 1.356-3887, 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
ABSTRACT
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.
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@#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.
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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.
Subject(s)
Humans , Alcoholics , Fibrosis , Hepatic Veins , Hepatitis, Alcoholic , Liver Cirrhosis, Alcoholic , Microbubbles , Mortality , Odds Ratio , Pilot Projects , Prognosis , Prospective Studies , ROC Curve , Survival Rate , Ultrasonics , UltrasonographyABSTRACT
Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.
Subject(s)
Humans , Acetaldehyde , Adrenal Cortex Hormones , Alcohol Drinking , Alcoholics , Biopsy , Carcinoma, Hepatocellular , Diagnosis , End Stage Liver Disease , Fibrosis , Genome, Human , Hepatitis, Alcoholic , Liver , Liver Cirrhosis , Liver Diseases, Alcoholic , Liver Transplantation , Malnutrition , Mortality , Prognosis , Recurrence , Risk Factors , Tissue DonorsABSTRACT
Objective To systematic review the clinical efficacy and safety of infliximab in treatment of severe alcoholic hepatitis (SAH).Methods The electronic database of PubMed,EMbase,Web of Science,OVID and Cochrane systematic review database,CBM disc and CNKI from building the database until March 2013 were retrieved.With SAH,severe alcoholic hepatitis,infliximab and tumor necrosis factor as key words or free words.Randomized-controlled trials (RCT) on infliximab in treatment of SAH was selected and analyzed by Meta analysis.Results Two RCTs was enrolled,included 56 SAH patients.Infliximab (10 mg/kg) combined with glucocorticoids (40 mg/d) might accelerate death because of the high prevalence of serious infections.Infliximab (5 mg/kg) combined glucocorticoids (40 mg/d) had more tolerability and improved patient's Maddrey scores significantly.Conclusions Existing clinical evidence suggest that it is short of evidence for the clinical efficacy and safety of infliximab.It need guide by large sample of clinically and different doses RCT.
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Objective To investigate the disease occurrence-related factors and severity of alcoholic hepatitis (AH) and alcoholic liver cirrhosis (ALC).Methods According to the clinical diagnostic criteria that were passed by the 2010 Chinese Society of Fatty Liver Hepatology and alcoholic liver disease study group,the clinical data of 241 AH and ALC patients were analyzed.Results The amount of liquor taken daily,the time limit of drinking,and total amount of liquor taken in ALC patients were significantly different from those in AH patients (P ＜0.01),respectively.In ALC patients,the proportion (48.39％)of workers,peasants,and unemployed low-income alcoholics was significantly higher than that (25.58％)in AH patients (P ＜0.01).Laboratory tests showed the AST/ALT ratio in the ALC group (2.63 ±4.74)was significantly higher than that in the AH group (1.01 ±0.52) (P ＜0.01); TG [(1.33±1.24)mmol/L] and cholesterol (CHOL) [(3.14 ± 1.25) mmol/L] in ALC group were significantly lower than TG [(2.29 ± 1.60)mmol/L] and CHOL [(4.27 ±0.79)mmol/L] in the AH group (P ＜0.01).Conclusions Alcoholic liver disease occurrence and severity were related to the amount of liquor taken,the time limit of drinking,and the work ; AST/ALT ratio,TG and CHOL values were consistent with the severity of alcoholic liver disease.
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Objective To observe the therapeutic effect of compound glycyrrhizin on alcoholic hepatitis.Methods A total of 65 patients with alcoholic hepatitis were assigned to group A(30 cases) treated with abstinence of alcohol,physical exercise and adjusted diet, and group B(35 cases) treated with compound glycyrrhizin together with the treatment given to group A. Before and after receiving three 4-week treatment periods, all the patients had their liver function tested and received examination of ultrasonic weave type B. Results Group B had significantly alleviated clinical symptoms, and ACT,A ST, GGT in blood serum are significantly lower than group A(P＜0.05).Examination of ultrasonic wave type B on the liver shows significant amelioration and disappearance of symptoms of fatty liver. Conclusion Compound glycyrrhizin can significantly ameliorate the clinical symptoms and improve the liver function of the patients.
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No abstract available.