Influencing factors for direct-acting antiviral therapy failure in treatment of hepatitis C / 临床肝胆病杂志

Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

Virological response to direct-acting antiviral therapy and changes in liver fibrosis indices in chronic hepatitis C patients with different alanine aminotransferase and aspartate aminotransferase levels in a real-world setting / 临床肝胆病杂志

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Significance of pathogen detection in patients with ventilator-associated pneumonia and changes of PCT,CRP and pulmonary function / 国际检验医学杂志

Objective To investigate the pathogenic characteristics of patients with ventilator associated pneumonia ,and analyze the correlation with the changes of serum procalcitonin (PCT ) ,C reactive protein (CRP) and pulmonary function .Methods 110 cases of patients with ventilator associated pneumonia was selected in a hospital from October 2014 to October 2016 as pathogenic groups .At the same time ,patients treated with ventilator adjuvant therapy for the same period without infection as non-pathogenic group (120 cases) ,selecting the same period of physical examination no abnormal patients as the healthy group (95 cases) ,detection and analysis of pathogenic characteristics in patients with ventilator associated pneumonia , detection of the serum levels of PCT ,CRP and lung function .Analyzed the correlation with the changes of ser-um PCT ,CRP and pulmonary function .Results 210 strains of pathogens were isolated from the secretions of 110 patients with pathogenic groups ,among them ,90 strains of Gram-positive bacteria accounted for 42 .85%, Gram-type negative bacteria accounted for 119 cases accounted for 56 .67% and a strain of fungus .The levels of PCT and CRP in the non-pathogenic group and pathogenic group were significantly higher than those in the healthy group ,the difference was statistically significant (P＜0 .05) .Serum PCT and CRP levels in the patho-genic group were significantly higher than those in the non-pathogenic group and the healthy group ,the differ- ence was statistically significant (P＜0 .05) .Logistic multiple regression analysis was used to analyze the inde-pendent risk factors of ventilator-associated pneumonia in patients .The duration of invasive ventilation ,gram-negative oropharyngeal bacteria count ,age and past history of COPD were independent risk factors ,with sig-nificant difference (P＜0 .05) .Patients in the pathogenic group had a forced expiratory volume (FEV1) ,forced vital capacity (FVC) ,forced expiratory force occupancy force ratio (FEV1/FVC) ,the first second percentage of forced vital capacity occupies vital capacity (FEV1%)were significantly higher than those in the non-patho-genic group and the healthy group ,the difference was statistically significant (P＜0 .05) .FEV1 ,FVC ,FEV1/FVC and FEV1% in the non-pathogenic group and pathogenic group were significantly higher than those in the healthy group ,the difference was statistically significant (P＜0 .05) .Conclusion Gram-negative bacteria predominate in ventilator-associated pneumonia .

Expression of ELMO1 in Hepatocellular Carcinoma and its Effects on Cell Migration / 现代医院

Objective To investigate the expression of engulfment and cell motility protein 1 (ELMO1) in hepatocellular carcinoma(HCC) and its effects on cell migration.Methods The expression of ELMO1 in HCC cell lines and HCC tissues was assessed by Western blot.We used transient transfection with an ELMO1 expressing vector to over-express ELMO1 protein in SK-HEP-1 cells.Over-expression of ELMO1 was confirmed by Western blot.siRNAs specific to ELMO1 (ELMO1 siRNA) were used to knockdown ELMO1 expression.Rho Family Small GTPase Activation Assay, Western blots, transwell assay were used to determine the migration potential of cells.Student's test was employed for statistical analysis.Results The expression of ELMO1 protein was obviously up-regulated in HCC tissues and cell lines (P<0.05).Over-expression of ELMO1 promoted cell migration in SK-HEP-1 cells, while knock-down of ELMO1 showed the opposite effect.Conclusion ELMO1 up-regulation significantly correlates with cell migration in hepatocellular carcinoma.

Kinetics of serum HBsAg in Chinese patients with chronic HBV infection with long-term adefovir dipivoxil treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Knowledge on Hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B (CHB) patients with long-term adefovir dipivoxil (ADV) treatment is limited. The aims of this study were to investigate HBsAg kinetics in patients with chronic hepatitis B virus (HBV) infection treated with long-term ADV and to evaluate different characteristics between patients with and without HBsAg loss.</p><p><b>METHODS</b>We retrospectively evaluated HBsAg kinetics in 24 Chinese patients with chronic HBV infection who achieved continuous virologic suppression during ADV therapy. HBV genotype was determined at baseline. Liver biochemistry, hepatitis B e antigen status, serum HBV DNA, and HBsAg levels were measured at baseline, 6 months, and once every year thereafter.</p><p><b>RESULTS</b>Of these 24 patients, 3, 1, and 20 patients were followed up for 3, 5, and 6 years, respectively. Baseline serum HBsAg level had a moderate correlation with baseline HBV DNA level (r = 0.52, P = 0.01). The median rate of HBsAg reduction during the therapy period was 0.08 lg IU × ml(-1) × y(-1). Baseline serum HBsAg level was significantly higher than other time points (P ranges from 0.046 to 0.002). The HBsAg reduction rate during the first year was similar to that in other years (P > 0.05). The HBsAg reduction rate during the first year in patients with eventual HBsAg loss was significantly faster than that in patients without HBsAg loss (P = 0.005).</p><p><b>CONCLUSIONS</b>Serum HBsAg levels in Chinese CHB patients receiving long-term ADV demonstrated a gradual reduction. Patients with eventual HBsAg loss had a significantly faster HBsAg reduction rate during the first year than those without HBsAg loss.</p>

Study on the Relation of Glycyrrhizic Glycoside on Hepatitis B Virus Replication in Vitro / 中国药房

OBJECTIVE:To study the relation of glycyrrhizic glycoside on hepatitis B virus(HBV)replication in vitro.METHODS:2.2.15cell line was used and treated with glycyrrhizic glycoside,the contents of HBsAg and HBeAg in the su?pernatant of cell culture with different concentrations of glycyrrhizic glycoside were quantified.RESULTS:The inhibitory rates of glycyrrhizic glycoside on HBsAg were83.8%,71.0%,62.1%,52.0%and29.7%respectively at the concentrations of800,400,200,100and50?g/ml respectively.CONCLUSION:Glycyrrhizic glycoside does not promote HBV replication in vitro experiment.

The detection of tumor necrosis factor-? and interleukin-6 in the ascitic fluid of cirrhotic patients compli cated.with spontaneous bacterial peritonitisand its significance / 中国实用内科杂志

Objective To investigate the clinical significance of tumor necrosis factor-?(TNF-?)and interleukin-6(IL-6)in the ascitic fluid of cirrhotic patients with spontaneous bacterial peritonitis(SBP).Methods TNF-? and IL-6 in the ascitic fluid of 32 cirrhotic patients with SBP were measured by ELISA.The group was compared with the value in transudatory ascites of 30 cirrhotic patients.Results The levels of TNF-? and IL-6 in the ascitic fluid of cirrhotic patients with SBP were much higher than those in transudatory ascites of cirrhotic patients(P