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ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.
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Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.
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Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.
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【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.
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Objective:To investigate the effect of transcatheter arterial chemoembolization (TACE) combined with ultrasound-guided radiofrequency ablation (RFA) on the efficacy and immune function in patients with primary liver cancer.Methods:The clinical data of 152 patients with primary liver cancer from February 2019 to February 2021 in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. Among them, 76 patients were treated with TACE combined with RFA (combined group), and 76 patients were treated with TACE (control group). The efficacy was compared; the α-L fucosidase, T lymphocyte subsets (CD 3, CD 4, CD 8 and CD 4/CD 8), B lymphocyte subsets (CD 19) and tumor markers (alpha-fetoprotein, AFP; carcinoembryonic antigen, CEA; carbohydrate antigen 125, CA125) before treatment and 1 month after treatment were detected. Results:The total clinical effective rate in combined group was significantly higher than that in control group: 81.58% (62/76) vs. 52.63% (40/76), and there was statistical difference ( χ2 = 4.54, P<0.05). There were no statistical difference in all indexes before treatment between 2 groups ( P>0.05); the α-L fucosidase, AFP and CD 8 1 month after treatment in combined group were significantly lower than those in control group: (18.06 ± 5.33) U/L vs. (26.58 ± 7.75) U/L, (87.93 ± 22.55) μg/L vs. (146.83 ± 21.85) μg/L and 0.295 ± 0.052 vs. 0.367 ± 0.064, the CD 3, CD 4 and CD 4/CD 8 were significantly higher than those in control group (0.489 ± 0.054 vs. 0.462 ± 0.063, 0.363 ± 0.059 vs. 0.303 ± 0.075 and 1.43 ± 0.27 vs. 0.89 ± 0.14), and there were statistical differences ( P<0.01 or<0.05); there was no statistical difference in CEA, CA125 and CD 19 1 month after treatment between 2 groups ( P>0.05). Conclusions:TACE combined with RFA in the treatment of primary liver cancer patients can not only improve the total clinical effective rate, but also significantly improve the immune function, and help to reduce level of the liver tumor marker of AFP.
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【Objective】 To screen the differentially expressed immune genes between responders （Rs） and non-responders （NRs） in chronic hepatitis B patients receiving interferon alpha （IFN-α） treatment and to explore the molecular basis of IFN-α treatment failure. 【Methods】 The gene expression profile GSE27555 which contained 6 Rs and 7 NRs was obtained from the Gene Expression Omnibus （GEO） database； then differentially expressed genes between liver tissues of Rs and NRs were selected by the R software. The iconic immune gene set consisting of 1793 genes was downloaded from the immunology database and analysis portal （ImmPort）. The immune genes were extracted from the differentially expressed genes to obtain the differentially expressed immune genes. Subsequently， Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the differentially expressed immune genes were performed by the R software. Protein-protein interaction （PPI） network of the differentially expressed immune genes was constructed using the STRING online tool. The plugin CytoHubba of the Cytoscape software was applied to identify the top 10 genes by using Degree， MCC， MNC， and Closeness algorithms； then the intersection was taken to obtain the hub genes. 【Results】 A total of 88 differentially expressed immune genes， consisting of 13 upregulated and 75 downregulated genes， were identified between Rs and NRs. GO analysis showed that the differentially expressed immune genes were significantly enriched in T cell activation， cell chemotaxis， regulation of cell-cell adhesion， antigen processing and presentation. KEGG pathway analysis suggested that the differentially expressed immune genes were significantly enriched in cytokine-cytokine receptor interactions， Th cell differentiation， antigen processing and presentation， interactions between viral proteins and cytokines and cytokine receptors， chemokine signaling pathways， T cell receptor signaling pathway， IL-17 signaling pathway， natural killer cell-mediated cytotoxicity， Toll-like receptor signaling pathway， and other immune response signaling pathways. The top 7 hub genes， identified by the plugin cytoHubba of the Cytoscape software by using Degree， MCC， MNC and Closeness algorithms， were CD8A， IFNG， CCL2， CCL5， CXCL10， CCL4， and FCGR3A. 【Conclusion】 This study made a comprehensive analysis of the differentially expressed immune genes and signal pathways between Rs and NRs by bioinformatics， and identified 7 Hub genes related to the ineffectiveness of IFN-α treatment in CHB patients. These hub genes may serve as potential biomarkers for predicting the response of IFN-α treatment in CHB patients.
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【Objective】 To construct and verify a model for predicting the prognosis of liver cancer patients with autophagy-related long non-coding RNA (LncRNA) expression. 【Methods】 LncRNA expression spectrum, mRNA expression spectrum and clinical characteristics of 374 patients with liver cancer were obtained from the Cancer Genome Atlas (TCGA) Database. The expression levels of autophagy-related genes (from the Human Autophagy Database) were extracted from the mRNA expression profile, and the LncRNA was screened to obtain the highly relevant autophagy-related genes by correlation analysis with the LncRNA expression profile. Differential expression analysis and single factor analysis were conducted between the expressions of the above established autophagy-related LncRNA in 374 cancer tissues and 50 normal tissues to screen autophagy LncRNAs which were differentially expressed and was associated with a significant liver cancer prognosis. The above screened LncRNA were included in the risk of Cox proportional model selection and the prognosis of patients with liver cancer prediction model was established. The risk index (risk score) was calculated according to the forecast model and patients could be divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, Cox regression analysis and receiver operating characteristic curve (ROC) were conducted to evaluate the prognostic value of the model. Gene set enrichment analysis (GSEA) was carried out to analyze the signal pathway of gene enrichment in patients with a high or a low risk. 【Results】 We screened 582 autophagy LncRNAs (R≥0.6, P<0.001) to obtain 23 LncRNAs which were differentially expressed and associated with a significant liver cancer prognosis. A prognostic model consisting of 6 LncRNAs, namely, MKLN1-AS, AC012360.3, AC145207.5, AL513320.1, AC099850.3 and AL049840.2 were constructed. KM survival analysis showed that the survival time of the high-risk group was significantly lower than that of the low-risk group (median survival time: 6.937 years and 2.323 years, P<0.001). Cox regression analysis showed that the survival time of patients in the high-risk group was significantly lower than that in the low-risk group (HR=3.773, 95% CI: 2.252-6.322, P<0.001); the area under the time dependent ROC curve for 1, 2, 3, 4, 5 and 6-year overall survival was 0.760, 0.729, 0.731, 0.722, 0.696 and 0.685. GSEA analysis showed that the genes in the high-risk group were mainly concentrated in cell cycle, autophagy, tumor, ubiquitin-mediated proteolysis, and RNA degradation. 【Conclusion】 The prognostic model composed of MKLN1-AS, AC012360.3, AC145207.5, AL513320.1, AC099850.3 and AL049840.2 can be used to predict the prognosis of liver cancer patients, which is expected to guide clinical treatment.
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ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.
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Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.
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Immune tolerance refers to the specific non-response or negative response of T and B lymphocytes to antigens.According to the period of formation,immune tolerance can be classified into central tolerance and peripheral tolerance.Immune tolerance to hepatitis B virus (HBV) after HBV infection is considered a major cause of chronic HBV infection.This article briefly reviews the roles of HBeAg,functional defects of dendritic cells,low response of cytotoxic T lymphocytes,T helper cells and cytokines,variations of HBV genotype and genome,and host gene polymorphisms in the development of immune tolerance in chronic HBV infection,as well as related research advances.