| Objective:The study analyzed the effect of artificial liver in chronic plus acute liver failure through clinical data analysis to examine the factors affecting the prognosis of patients with ACLF under artificial liver treatment.We further adopted the high-performance gas chromatography-mass spectrometry(GC-MS)method to analyze the serum metabolite profiles of patients with chronic acute liver failure,patients with chronic hepatitis B patients,healthy volunteers,and ACLF patients before and after the therapy,with an aim to identify serum-specific markers applicable for the diagnosis and prognosis of ACLF regarding the metabolomic level.The metabolite spectrum of each group was compared to reveal the pattern of substance changes during the development of liver disease.And we evaluated the effectiveness of blood metabolomics for real-time dynamic monitoring of changes in acute liver failure,.Subjects and Methods:1.Study subjects: A total of 137 subjects were included in this study,including75 patients with acute-on-chronic liver failure,30 with chronic hepatitis B,32 healthy control group members,2.Research methods:The clinical data of the study subjects were recorded with blood samples collected.Firstly,all ACLF patients were divided into 25 patients in the group of medical treatment combined with artificial liver treatment(artificial liver treatment group)and 50 patients in the group of medical treatment only(control group).The clinical symptoms and biochemical test indexes were compared between the two groups to determine the efficacy of the artificial liver and to analyze the factors related to the prognosis of ACLF.Results:1.Notable improvement of clinical symptoms(jaundice,weakness,nausea,vomiting,etc.)was observed in both the artificial liver treatment group and the medical treatment group.The patients in the artificial liver treatment group showed more significant improvement in symptoms than those in the medical treatment group.2.Hemoglobin,glutathione transaminase,glutamic oxalacetic transaminase,total bilirubin,international normalized ratio,and MELD score have all decreased in the artificial liver group after ALSS treatment(p<0.05),while prothrombin time activity and sodium ion increased(p<0.05).3.The comparison of the treatment efficiency of patients in different ACLF stage groups revealed that the efficiency of early and middle stage of ACLF in the artificial liver treatment group was higher than that in the control group(p<0.05),but the difference in the efficiency of the late stage of ACLF treatment between the two groups was not statistically significant(p>0.05)4.In this study,GC-MS was used to analyse the serum samples of ACLF group and CHB group and healthy control group to obtain GC-MS analytical chromatogram-ms,and significant differences were found in some chromatographic peaks of CHB group compared with those of people in healthy control group and ACLF patients.There were also significant differences in serum metabolites before and after artificial liver treatment in patients with acute liver failure.5.Using the principal component analysis(PCA)model and OPLS-DA clustering analysis of ACLF group,chronic hepatitis B group and healthy control group,the ACLF model could be successfully established with the three groups clearly distinguished.RF method was used to classify the characteristic metabolites in the acute-on-chronic liver failure group,chronic hepatitis B group,healthy control group,and patients with acute liver failure before and after artificial liver treatment,and then multidimensional scaling maps were obtained,and the results showed that the metabolic profile of ACLF patients was significantly different from that of CHB patients and healthy volunteers.There were significant differences in serum metabolites before and after artificial liver treatment in patients with acute liver failure.6.RF algorithm was used to analyze the distribution and classification of amino acid,carbohydrate and fatty acid metabolites in the three groups of samples as well as the samples before and after artificial liver treatment in detail and determine the importance of metabolites variablea in each group.Substances which show significant differences in samples from the acute-on-chronic liver failure group,chronic hepatitis B group,and healthy control group included boric acid,2-(methoxyimino)-propionic acid,glycine,L-methionine,aminomalonic acid,glycerol monostearate,and cholesterol.Substances with significant differences before and after artificial liver treatment included 2-(methoxyimino)-propionic acid,lactic acid,L-methionine,aminomalonic acid,and cholesterol.Further comparison of the changes of the above characteristic substances between the groups showed that threonine,L-methionine,phenylalanine,and cholesterol were significantly increased in acute-on-chronic liver failure compared with chronic hepatitis group and healthy control group,while glycine,aminomalonic acid,glycerol monostearate,boric acid,and 2-(methoxyimino)-propionic acid were decreased in ACLF levels.7.In this study,the correlation between characteristic metabolites which help with prognosis disease monitoring and MELD score was analyzed,indicating that these characteristic metabolites had a close correlation with MELD score,in which threonine,methionine,phenylalanine,and cholesterol were positively correlated with MELD score,while glycine,aminomalonic acid,glycerol monostearate,boric acid,and 2-(methoxyimino)-propionic acid were negatively correlated with MELD score.Conclusions:1.artificial liver treatment is conducive to improve liver function and coagulation indexes such as ghrelin,ghrelin,serum total bilirubin,international normalized ratio,prothrombin time activity,etc.in patients with ACLF.In addition,early intervention with artificial liver therapy can increase the treatment efficiency of patients with early and mid-stage chronic acute liver failure.2.GC-MS was used to study the serum metabolomics of the patient group with acute-on-chronic liver failure,chronic hepatitis B group,healthy control group and group with acute liver failure and artificial liver treatment.It was found that there were a variety of differential metabolites between the groups,and through the comparison of metabolite profiles,specific markers with severe liver failure and prognosis could be identified.Therefore,serum metabolomics has great potential for dynamic monitoring of changes in the condition of liver failure and evaluating the therapeutic effect of artificial liver. |
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