Identification of Function and Mechanism of Apolipoprotein H Gene in Liver Failure Based on Bioinformatics Analysis / 中山大学学报(医学科学版)

@#【Objective】To explore the function and mechanism of differentially expressed Apolipoprotein H（APOH） gene in liver failure by bioinformatics. 【Methods】Multiple chip datasets（GSE14688，GSE38941 and GSE96851） were downloaded from the Gene Expression Omnibus （CEO）database. The differentially expressed genes were screened out based on P value < 0.05 and |log2FC| > 5. Biological function enrichment and KEGG pathway analysis of APOH gene， which was among the top ten key genes screened，was analyzed by Cytoscape and R，for further validation of expression of APOH in chronic hepatitis B virus-related liver failure.【Results】A total of 2 438 differentially expressed genes were screened，among which 1 162 were significantly up-regulated and 1 276 were significantly down-regulated. According to Protein-protein Interaction Network（PPIN）analysis，the top ten key genes were KNG1，IGF1，SPARC，APOH，CLU， SERPING1，TGFB2，CDC37L1，PCYOX1L and APOOL. High expression of APOH was found in chronic hepatitis B virus- related liver failure tissues and GeneMANIA predicted that APOH was associated with inflammation. GO analysis and KEGG analysis showed that APO，which was closely related to complement/coagulation cascade pathway and carbon metabolism pathway，positively correlated with C3（complement C3）.【Conclusion】APOH is involved in the occurrence and development of liver failure by C3 regulating complement/coagulation cascade pathway and carbon metabolism pathway.

Sleep Status of Patients with Chronic Hepatitis B Virus Infection / 中山大学学报(医学科学版)

@#【Objective】To investigate the sleep status of patients with chronic HBV infection【Methods】From January 2019 to June 2019 ，353 patients with chronic hepatitis B virus infection in the outpatient department of the Third Affiliated Hospital of Sun Yat-sen University，using the sleepiness scale，insomnia scale，sleep quality scale，anxiety self- rating form and depression self- evaluation ，patients were scored and grouped according to sleep grading criteria. Patients were collected for gender，age，disease diagnosis，antiviral therapy，and educational level. Chi-square correlation test and multivariate logistic regression were applied to analyze the influencing factors of sleep. 【Results】 The overall sleepiness rate was 47.88%. The overall insomnia rate was 53.26%. There were 6.8% patients who had poor sleep quality. The risk factor of lethargy was the degree of anxiety（P = 0.000，OR = 3.076，95% CI 1.706~5.545）. The risk factor of insomnia was anxiety（P = 0.000，OR = 14.693，95% CI 5.046~42.782）and depression（P = 0.002，OR = 2.279，95% CI1.340~3.877）. The risk factor of sleep quality was anxiety（P = 0.000，OR = 9.990，95% CI 4.031~24.758）.【Conclusions】 Patients with chronic HBV infection have a high proportion of subjective sleep disorders. The main influencing factor is mental state of the patient. A full understanding of the patients′ sleep status will help the patients′ treatment.

Programmed death-1 (PD-1) and PD-L1 expression during antiviral treatment of chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study PD-1 and PD-L1 expressions during 24 weeks telbivudine antiviral treatment in patients with chronic hepatitis B (CHB) and to explore the relationship between PD-1 expression and HBeAg/HBeAb seroconversion.</p><p><b>METHODS</b>Ten CHB cases with HLA-A2 and HBeAg positive were treated with telbivudine 600 mg/d orally for 24 weeks. Fresh blood samples were collected at week 0, 12 and 24 after treatment. HBV-specific CD8+ T cells were expanded in vitro. Cell culture medium were collected for interferon gamma (IFNgamma) detection. Flow cytometry was used to detect the HLA-A type, PD-1, PD-L1 and HBV specific CD8+ T cells. The expressions of PD-1 and PD-L1, the counts of HBV-specific CD8+ T cells in circulating CD8+ lymphocytes, and IFNgamma concentration in culture medium were evaluated during antiviral treatment.</p><p><b>RESULTS</b>At week 0, 12 and 24 after telbivudine treatment, 7 of 10 patients were HBV DNA undetectable, 2 were HBeAg seroconversion and 2 were HBeAg lose but anti-HBe negative. The frequency of PD-1-positive PBMCs were 52.1%+/-17.0%, 39.1%+/-18.2% and 23.4%+/-16.3% (week 24 vs week 0, P < 0.01) respectively; PD-L1 positive PBMCs were 45.6%+/-15.4%, 34.6%+/-16.2% and 20.9%+/-9.5% respectively(week 24 vs week 0, P < 0.01; week 24 vs week 12, P < 0.05). The frequency of PD-1-positive CD8+ T cells were 76.2%+/-10.4%, 66.5%+/-15.4% and 49.5%+/-25.3% respectively (week 24 vs week 0, P < 0.01; week 12 vs week 0, P < 0.05; week 24 vs week 12, P < 0.05); HBV-specific CD8 cells were 1.3%+/-0.5%, 1.5%+/-1.0% and 2.2%+/-1.5%; IFNgamma levels in cell culture medium were (91.7+/-82.1) pg/ml, (99.4+/-93.5) pg/ml and (109.5+/-86.6) pg/ml. A remarkable decrease of PD-1 and PD-L1 expressions and increase of HBV-specific CD8+ T cells were observed in patients who had HBeAg/HBeAb seroconversion at week 24.</p><p><b>CONCLUSIONS</b>Direct suppression of HBV replication by telbivudine in CHB patients can decrease PD-1 and PD-L1 expressions and restore HBV-specific CD8+T cells. The relationship between the changes of PD-1 expression and HBeAg/HBeAb seroconversion during antiviral therapy in HBeAg-positive patients need to confirm by future study.</p>

The effects of diethylene glycol on liver function / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the hepatotoxic effects of accidental intravenous diethylene glycol (DEG.) poisoning in patients with liver disease.</p><p><b>METHODS</b>Clinical data and liver function results were obtained from 64 patients with liver diseases who had been accidentally treated with diethyl glycol-contaminated agent and 45 cases with hepatorenal failure. The hepatotoxic effects of diethylene glycol DEG on the patients with liver diseases were assessed by multivariable logistical regression analysis.</p><p><b>RESULTS</b>Of the 64 cases with liver diseases, 15 cases (23.4%) developed toxic presentations following the accidental administration of DEG. All affected cases were male. Twelve of the 15 poisoned patients (80%), died within 7 days of exposure to DEG. The most common clinical manifestations included kidney damage, renal failure, metabolic acidosis, and nerve system disturbances. The intravenous administration of DEG resulted in only mild liver function impairment. In terms of risk factors, both gender (r = 4.266, P less than 0.05) and the severity of jaundice prior to DEG administration were related to the occurrence of toxin-induced renal failure (r = 7.640, P less than 0.01).</p><p><b>CONCLUSIONS</b>DEG may worsen liver damage in patients with liver diseases.</p>

Study on characteristics of cellular-mediated immune responses of novel H1N1 influenza A patients with pneumonia / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the phenotype, frequency and function of CD4+ T cell subsets and the relevant cytokines, as well as the relationship between these cells and appearance of pneumonia of novel (H1N1) influenza A patients.</p><p><b>METHODS</b>68 healthy people, 53 confirmed novel A(H1N1) influenza patients without pneumonia and 16 confirmed severe novel A (H1N1) influenza patients with pneumonia were enrolled in this study. Viral load in nasopharyngeal swabs specimens was measured by real time PCR assay. The phenotype and percentage of CD4+ T cell subsets including Th1, Th2, Th17, and Treg cells were measured by Flow cytometry analysis. The relevant cytokines in plasma including TGF-beta, IL-6 and IFN-gamma were measured by ELISA. Data was analyzed by one way ANOVA.</p><p><b>RESULTS</b>It was found that peak viral load and viral shedding period of severe patients with pneumonia was significantly increased compared with mild patients without pneumonia (P < 0.05). The percentage of Th17 cells of severe patients with pneumonia was significantly diminished compared to that of healthy subjects and mild patients without pneumonia (P < 0.05). However, Th1, Th2, Treg cells frequencies had no significant differences (P > 0.05) among these three groups. The level of TGF-beta in plasma for the severe patients with pneumonia was also significantly decreased compared to that of healthy subject and mild patients without pneumonia (P < 0.05). The viral shedding period inversely correlated with the frequency of Th17 cells (r = - 0.38, P < 0.05).</p><p><b>CONCLUSION</b>H1N1 influenza A virus can inhibit Th17 cells to differentiate, particularly more extent in patients with pneumonia. Impaired Th17 cells may correlate with viral clearance and pneumonia of novel H1N1 influenza A patients.</p>

Specific T cell immune response in chronic hepatitis B patients treated with different doses of recombinant hepatitis B vaccine / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the specific cellular immunoresponse of peripheral blood lymphocytes in the chronic hepatitis B patients treated with different doses of recombinant hepatitis B vaccine.</p><p><b>METHODS</b>Seventy-two chronic hepatitis B patients who did not use any anti-HBV drugs within 6 months were randomized into 3 groups (90 micrograms, 60 micrograms, and placebo) in a ratio of 1:1:1. The patients in different groups were treated with different doses of recombinant hepatitis B vaccine in combination with IFN alpha 1b 50 micrograms with 3 times a week for 24 weeks. All patients were followed up for 24 weeks (W24). HBV DNA, HBeAg and liver functions were detected at different time points, and the number of cells that secrete IFN-gamma were detected by ELISPOT.</p><p><b>RESULTS</b>There were no significant difference in ELISPOT positive ratio among the 3 groups on baseline detection. At W24, 12 cases, 12 cases, and 7 cases showed ELISPOT positive in the group of 90 micrograms, 60 micrograms, and placebo. The proportion of patients who were ELISPOT positive was higher in the groups treated with recombinant hepatitis B vaccine (including the dose of 90 micrograms and 60 micrograms) than that in the placebo group (P=0.0446). HBV DNA turned negative in 6/24 of the patients treated with recombinant hepatitis B vaccine (at both the doses of 90 micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion or HBeAg became negative in 7/24 of them. In the placebo group, none of the patients showed undetectable HBV DNA, HBeAg/Anti-HBe seroconversion or HBeAg disappearance. At the 24W of follow up, in the patients who were ELISPOT positive, HBV DNA became undetectable in 4 of the patients treated with recombinant hepatitis B vaccine (at doses of 90 micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion or HBeAg disappearance were found in 9 of the cases. In the placebo group, none of the cases showed undetectable HBV DNA, and only 1 case had HBeAg/Anti-HBe seroconversion.</p><p><b>CONCLUSION</b>The recombinant hepatitis B vaccine may increase the function of specific T lymphocytes in patients with chronic hepatitis B. There were no significant differences between the patients treated with the dose of 90 micrograms and 60 micrograms hepatitis B vaccine.</p>

Venous diethylene glycol poisoning in patients with preexisting severe liver disease:a clinical analysis / 中华传染病杂志

Objective To describe the clinical features of venous diethylene glycol poisoning and to identify factors correlating with such kind of poisoning.Methods Retrospective chart review was performed to analyze the epidemiology,clinical presentation,hepatorenal functions,bemodynam- ics and pathological characteristics of 64 patients with severe liver diseases who received intravenous diethylene glycol.Comparative analyses of correlating factors and causes of poisoning were based on the presence or absence of poisoning.Results Fifteen cases of poisoning were reported.After a 5 day incubation period,all poisoned patients displayed acute renal failure and 11 cases with digestive tract symptoms and(or) symptom exacerbations were noted.Neurological system impairment was observed in 10 cases after 2 weeks.Metabolic acidosis developed in 13 cases.Poisoned patients exhibited signif- icantly lower red blood celI(RBC)[(2.32?0.76)?10~(12)/L],hemoglobin(Hb) [(79.5?23.6)g/L] value and higher white blood cell(WBC)[(9.78?3.75)?10~9/L] count.Renal biopsy of poisoned patients revealed acute tubular necrosis and interstitial nephritis.Twelve poisoned patients died.Sig nifieant differences were found between groups regarding preexisting severe hepatitis,ascites,renal disease and diuretic therapy.Prior to diethylene glycol injections,mean values of neutrophil,blood urea nitrogen(BUN),creatinine(Cr) and calcium and phosphorousions differed significantly between groups.Conclusions Features of venous diethylene glycol poisoning include oliguric acute renal fail- ure,metabolic acidosis,digestive symptoms,nervous system impairment and a high probability of anemia and WBC proliferation.Mortality is high.Correlative factors include preexisting severe liver disease,renal disease and infection.

The clinical features and natural history of post-transfusion hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the clinical features and natural history of post-transfusion hepatitis C (PTHC).</p><p><b>METHODS</b>Ninety-nine post-transfusion hepatitis C patients were analyzed using retrospective and prospective study and follow-up.</p><p><b>RESULTS</b>(1) Ninety-nine post-transfusion HCV patients were infected during 1989-1994, mostly between 1990-1992. (2) Ninety patients were diagnosed as chronic hepatitis C, and 9 as hepatic cirrhosis (period of compensation). (3) The intervals between their transfusions and their initial diagnoses of PTHC were 7.4+/-6.6 years in all 99 patients, and the intervals in 9 cirrhosis patients were 12.7+/-5.8 years. (4) Among 63 male patients, 59 cases were chronic hepatitis C and 4 were cirrhosis while among 36 female patients, 31 were chronic hepatitis C and 5 were cirrhosis. There was no significant difference of the ratio for hepatitis C and cirrhosis between the male and female patients (P>0.05). (5) Repeat abnormal liver function occurred accompanied with a fluctuation of ALT elevation in those patients with cirrhosis. (6) No patient developed hepatic carcinoma during the study period.</p><p><b>CONCLUSIONS</b>(1) The possibility of HCV infection by transfusion has declined greatly since 1995 in Guangzhou. (2) Nine of the 99 (9.1%) chronic HCV-infected patients developed a compensated cirrhosis after 12.7+/-5.8 years. (3) For those PTHC patients with repeat abnormal liver functions, interferon combined with ribavirin is recommended to prevent the development of cirrhosis.</p>

Changes of antigen-specific cytotoxic T lymphocytes during acute flare-ups in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To detect HBV antigen specific cytotoxic T lymphocyte (CTL) changes in patients during acute flare-ups and to study their association with flare-ups and aggravations into grave hepatitis by quantitative analysis of HLA-A2* restricted HBcAg-specific CTL cells.</p><p><b>METHODS</b>The frequency of HBcAg-specific CTL cells in the peripheral blood mononuclear cells (PBMC) from 29 patients with persistent infection with HBV were quantified by flow cytometry using one HLA-A2*HBV peptide pentamers complex (Pro5TM MHC Pentamers).</p><p><b>RESULTS</b>There was a statistical difference of HBcAg specific CTLs between the patients with acute exacerbations (1.4%+/-0.8%) and the patients with immune tolerance (0.6%+/-0.4%) (t = 2.180, P = 0.01-0.05); There was no significant difference between the grave hepatitis group (1.3%+/-1.0%) and the chronic hepatitis group (1.4%+/-0.8%) regarding frequencies of antigen specific CTL (t = 0.215, P = 0.833-0.05). The level of antigen specific CTLs in PBMC in the 6 cases of chronic hepatitis B with acute exacerbations maintained a relatively high level (more than 0.7%) within the 12 week follow-up period.</p><p><b>CONCLUSION</b>HBcAg-specific CTLs may play an important role in hepatic flare-ups in patients with chronic HBV infection, but there was no direct relationship between antigen- specific CTLs and grave hepatitis.</p>

Pathological changes of the livers from 39 patients with hepatic failure / 中华传染病杂志

Objective To explore the pathological changes of the livers from hepatic failure (HF)patients and its association with clinical disease stages.Methods Thirty-nine patients with liver failure caused by HBV infections were investigated,and none accompanied with hepatocellular carci- noma.The sections of tissue were taken from the liver after liver transplantation and stained with he- matoxylin eosin(H&E)or RT(reticular fiber)staining.The pathological features were analyzed and compared between the clinical and pathological diagnosis.Results 1.The range and the grade of the pathological changes were all well-proportioned in the whole liver but quite asymmetrical in the same spicemen.2.4 cases with clinical diagnosis of cirrhosis(active stage)were in accordance with the pathological diagnosis.Only 17 in 35cases can be pathologically diagnosed as chronic severe hepatitis (SH),while the other 18 cases were pathologically diagnosed as cirrhosis(active stage).Conclu- sion There were a great inconsistency between the clinical and pathological diagnosis.