Objective To explore the efficacy of sequential or combined amphotericin B (AmB) and fluconazole (FCZ) therapy on a 5 flucytosine based regimen in non-acquired immunodeficiency syndrome (AIDS)-related cryptococcal meningitis.Methods A tatal of 117 cases of non-AIDS-related cryptococcal meningitis treated with 5-flurocytosine-based regimens were retrospectively divided into five groups:AmBgroup (n=38),FCZ group (n=25),FCZ and AmB sequential group (n=18),AmB and FCZ sequential group (n=15),AmB and FCZ combination group (n=21).The number in cerebrospinal fluid (CSF) of the five groups were compared.Statistical analyses included t test,oneway analysis of variance,K-independent samples test and chi-square test.Results Intracranial pressure of AmB group,FCZ group,FCZ and AmB sequential group,AmB and FCZ sequential group,AmBandFCZ combination group were (208.6±75.1),(191.5±94.5),(185.0±76.3),(201.9±69.7) and (223.1±89.3) mm H2O (1 mm H2O=0.0098 kPa),respectively,and the differences were not statistically significant (F=0.611,P =0.656).Median cryptococcus counts in CSF of the five groups were 0,10,0,3 and 0/mL,respectively,with no statistical significance (x2 =7.638,P-0.090).CSF protein levels of the five groups were 0.55,0.69,0.67,0.53 and 0.96 g/L,respectively,with no significant differences among groups (F=7.063,P=0.133).The cure rates of the five groups were 55.3％ (21/38),32.0％ (8/25),9/18,6/15 and 47.6％ (10/21),respectively;progression rates or mortality of the five groups were 28.9％ (11/38),44.4％ (11/25),5/18,4/15and 23.8％ (5/21),respectively; and the differences among cure rates (x2 =3.638,P=0.457) and progression rates or mortality (x2-2.785,P =0.604) were not statistically significant.Conclusion FCZ or AmB alone,sequential or combined therapy were all effective in the treatment of cryptococcal meningitis.

ObjectiveTo investigate the therapeutic effects of patients with non-acquired immunodeficiency syndrome ( AIDS )-related cryptococcal meningitis treated with fluconazole and flucytosine.MethodsA retrospective study was conducted including 52 cases of non-AIDS-related cryptococcal meningitis,which were divided into two groups:the amphotericin B combined with flucytosine group (n =32) and the fluconazole combined with flucytosine group (n =20 ). The comparison between groups was done by t test and chi-square test.ResultsThe intracranial pressure of the amphotericin B combined with flucytosine group and the fluconazole combined with flucytosine group were (221.9±76.2) and (213.4±99.2) mm H2O,respectively (t=0.302,P＞0.05) ; the cryptococcus counts in the cerebrospinal fluid (CSF) were (351 ± 1180) and (508 ± 943)/mL,respectively (t=- 0.473,P＞0.05) ; the CSF protein levels were (0.754 ± 0.726) and (0.649 ±0.308) g/L,respectively (t=0.578,P＞0.05) ; the CSF white blood cell (WBC) counts were (16±25) × 106/L and (28±32) × 106/L,respectively (t=-1.348,P＞0.05).The cured rates were 59.38％ (19/32) and 35.00％ (7/20),respectively in the amphotericin B combined with flucytosine group and the fluconazole combined with flucytosine group,and the improved rates were 6.25％(2/32)and 25.00％ (5/20),respectively,the uncured or mortality rates were 34.38％ (11/32) and 40.00％ (8/20),respectively,and the difference were not significant of cured rates (x2 =2.925,P＞0.05) and uncured or mortality rates (x2 =0.168,P＞0.05) between two groups.ConclusionFluconazole combined with flucytosine also has a good effect on the treatment of cryptococcal meningitis.

Objective To evaluate the efficacy of entecavir treatment on hepatitis B patients with acute-on-chronic liver failure. Methods Eighty-four hepatitis B patients with acute-on-chronic liver failure were treated with entecavir 0.5 mg daily and Other routine drugs. Another 99 hepatitis B patients with acute-on-chronic liver failure were treated with only routine drugs as control. The survival, liver functions, hepatitis B virus (HBV) DNA level, prothrombin time (PT) were observed. The survival rates of patients with early, middle or late stage of liver failure were analyzed. The comparison of rates were done using chi-square test. The numeration data were compared by t test. The survival rates were compared using Kaplan-Meier method. Results Among patients with early stage of acute-on-chronic liver failure, the survival rate in treatment group was 63.3% (31/49), which was significantly higher than that in control group (39.7%, 23/58) (χ2=5.923, P=0.015). Among patients with middle stage of acute-on-chronic liver failure, the surviral rate in treatment group was 63.0% (17/27), which was significantly higher than that in control group (35.1%, 13/37) (χ2=4.854, P=0.028). Among patients with late stage of acute-on-chronic liver failure, four out of eight cases survived in treatment group, while one out of four cases survived in control group. In patients with serum total hilirubin (TBil) level > 342 μmol/L, the survival rate was 56.0% in treatment group, which was significantly higher than that in control group (26.8%) (χ2=9.351,P=0.002). At week 4 of the treatment, the HBV DNA reduction in treatment group was 3. 95 lg copy/mL, which was higher than that in control group (1.78 lg copy/mL) (t=5.847, P=0.001). Conclusions Entecavir treatment could improve the survival rate of hepatitis B patients with early or middle stage of acute-on-chronic liver failure. And the further study with larger population is needed in patients with late stage of liver failure. In addition, entecavir therapy could also improve the survival rate of patients with TBil >342 μmol/L.

Objective To investigate the level of serum macrophage migration inhibitory factor (MIF) and its correlation with serum precollagen Ⅲ peptide (PⅢP) and tissue inhibitor of metalloproteinase (TIMP)-1 in patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-related cirrhosis. Methods Forty-four CHB patients (hepatitis B group), 44 patients with HBV-related cirrhosis (cirrhosis group) and 30 healthy controls (control group) were enrolled in this study. The venous blood was collected and MIF level was detected by enzyme-linked immunosorbent assay (ELISA). Correlations between MIF and PⅢP, TIMP-1 were analyzed in observed groups. Comparison between groups was done using t test. The correlations between MIF level and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), plasma thromboplastin antecedent (PTA), PⅢP and TIMP-1 were analyzed by rectilinear correlation. Results The levels of serum MIF, PⅢP and TIMP-1 in CHB group and cirrhosis group were all significantly higher than those in control group (t=12.87,5.28, 10.98,t=11.22,14.84,11.17;all P<0.05), while there were no significant differences between CHB group and cirrhosis group (t= -1.05,1.52,--2.07;all P>0.05). There was no correlation between MIF level and ALT, AST, TBil and PTA. MIF level in CHB patients with hepatitis B e antigen (HBeAg) positive and high viral load were both higher than that in patients with HBeAg negative and low viral load. MIF level was both positively correlated with PⅢP level in CHB group and cirrhosis group (r=0. 603, P<0.05 and r=0. 415, P<0. 05, respectively). MIF level was also positively correlated with TIMP-1 level in CHB group (r=0. 458, P<0.05), while not correlated in cirrhosis group (r=0. 210, P>0.05). Levels of PⅢP and T1MP-1 were both correlated in CHB group and cirrhosis group (r=0. 849, P< 0.05 and r=0. 424, P<0.05, respectively). Conclusions The levels of serum MIF are significantly increased both in patients with CHB and cirrhosis. The early production of MIF might be related with viral replication, but not with liver function. MIF participates in formations of hepatitis, liver fibrosis and cirrhosis, which could reflect the degree of liver cirrhosis.

Objective To understand the clinical features of hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfected patients with different virological profiles.Methods The clinical data of 186 patients with HBV/HCV coinfection from May 1999 to May 2010 in the Third Affiliated Hospital of Sun Yat-Sen University were analyzed retrospectively.The demographic data,epidemiological data,laboratory results and pathological index were analyzed.The statistical analysis was done using t test and chi square test.Results A total of 186 patients were divided into 4 groups:66(35.5%)in HBV DNA(-)/HCV RNA(-)group,8(4.3%)in HBV DNA(+)/HCV RNA(+)group,68(36.6%)in HBV DNA(+)/HCV RNA(-)group and 44(23.7%)in HBV DNA(-)/HCV RNA(+) group.The gender composition,complication incidence,transmission among drug users,alanine aminotransferase(ALT)level,total bilirubin(TBil)level,prothrombin activity(PTA)and hapatitis B e antigen(HBeAg)negative rate were all significantly different among four groups(F or x2=11.578,8.451,11.738,2.669,5.102,4.254 and 18.413,respectively;all P<0.05).In groups of HCV RNA(-)and HCV RNA(+),the proportions of patients infected through drug abuse were 49.3%and 23.1%,respectively(x2=9.987,P:0.002)and blood transfusion transmission were 29.9%and 46.2%,respectively(x2=4.412,P=0.036).When HBV DNA was negative,the median ALT levels in HCV RNA(-)and HCV RNA(+)patients were 177 U/L and 62 U/L,respectively(t=2.200,P<0.05),median TBil levels were 133 μmol/L and 20μmol/L,respectively (t=3.608,P<0.05)and PTA were 70.6%±27.7%and 83.3%±27.8%,respectively(t=-1.982,P<0.05).The HBeAg negative rate was not affected by HCV RNA levels(t=0.707,P>0.05).The HBeAg negative rate in HBV DNA(-)patients was 85.5%,which was higher than that in HBV DNA(+)patients(59.2%)(x2=16.393,P<0.05).Conclusions HBV DNA(+/-)/HCV RNA(-)profile were major components in HBV/HCV confection.HBV DNA level is related to disease progression and prognosis,but not relate to disease severity.Liver function damage and disease severity are aggravated with HCV RNA level decreases.HBV DNA level is related to HBeAg negative rate,while HCV RNA level is not related to HBeAg seroconversion rate.

Objective To investigate the therapeutic effects of recombinant yeast hepatitis B virus(HBV)vaccine combined with interferon(IFN)α-1b and determine the rational dosage of HBV vaccine for the further clinical study with larger sample.Methods Two hundreds and sixteen patients with chronic hepatitis B(CHB)were enrolled in this randomized,multi-center,double-blinded and placebo-controlled clinical trial.All the subjects were not treated with antiviral drugs within 6 months and randomly divided into 90μg,60μg and placebo groups with a ratio of 1:1:1.All the patients were intramuscularly administrated with 90μg or 60μg recombinant HBV vaccine or placebo at week 0,2,6,10,14,18,22,respectively.Meanwhile,they were also treated with IFNα-1b 50μg,3 times a wcek for 24 weeks.All patients were followed up for 24 weeks after withdrawal of anti-HBV therapy.Serum HBV DNA level,HBeAg titer and liver function were monitored frequently.Interferon-γ secreting lymphoeytes were detected by Enzyme-linked immunospot(ELISPOT)in part of the patients.Results The serum HBV DNA levels were(6.03±1.79),(5.52±1.82)and(6.29±1.70)log10 copy/mL at week 24 of treatment in high dose,low dose and placebo groups,respectively (P=0.458).And the serum HBV DNA levels were(5.92±1.98),(5.49±1.99)and(6.16±1.76)log10 copy/mL at weck 24 after withdrawal of treatment,respectively(P=0.720).The rates of patients whose HBV DNA＜1×105 copy/mL in these three groups were 30.4%,39.4% and 20.8% at week 24 of treatment,respectively and there was significant difference between high dose group and low dose group(P=0.015).The rate of patients whose HBV DNA＜1×105 copy/mL at week 24 after withdrawal was highest in low dose group,but no significant differences before and after treatment in these three groups(P=0.257).The HBV DNA negative rates were 17.4%,25.4% and 6.9% in these three groups,respectively,which were significantly different(P=0.012).At week 24 of treatment and week 24 after withdrawal of treatment,the alanine aminotransferase normalization rate,HBeAg seroconversion rate were highest in low dose group,but no significant differences in these three groups.ELISPOT positive rates at week 24 of treatment and week 24 after withdrawal of treatment in high close and low dose groups were higher than that in placebo group(P＜0.05).The incidence of adverse events was similar and there was no drug related severe adverse events in each group.Conclusion Recombinant HBV vaccine maybe contribute to anti-HBV therapy and 60μg of dosage seems to be rational.

Objective To retrospectively investigate the relapse rates of different duration of extended consolidation after withdrawal of nucleos(t) ide analogues (NAs) treatment in patients with chronic hepatitis B (CHB) who met NAs cessation criteria.Methods 102 CHB patients discontinued treatment according to NAs cessation criteria or extended duration of consolidation therapy after meeting the cessation criteria.30 patients meeting the cessation criteria were Group A.72 patients extending consolidation therapy after meeting the cessation criteria were Group B.Based on different duration of extended consolidation therapy,72 patients were divided into 3 groups.Patients with a duration of extended 12 months after meeting NAs cessation criteria were Group B1.Patients with a duration of extended 24 months were Group B2.Patients with duration of extended 36 months were Group B3.After cessation of NAs treatment,the cumulative relapse of different group was calculated by the Kaplan-Meier method.The cumulative relapses between the selected groups were analyzed with Log-rank test.Results The cumulative relapse rates after 6,12,18,24,36 and 48 months after cessation of NAs treatment were 52.3％,70.0％,74.3％,76.7％,82.4％ and 88.4％ in Group A;24.0％,38.8％,40.6％,43.3％,43.3％ and 43.3％ in Group B;respectively.The relapse rate of Group B was much lower than that of Group A.The cumulative relapse rates after 6,12,18,24,36 and 48 months after cessation of NAs treatment were 35.0％,48.2％,51.9％,57.9％,57.9％ and 57.9％ in Group B1;18.1％,30.7％,30.7％,30.7％,30.7％ in Group B2;7.1％,21.4％,21.4％,21.4％ in group B3;respectively.The relapse rate of Group B1 was the highest,the following was of Group B2,and of Group B3 was the lowest one.The total amount of relapse in Group A,B1,B2 and B3 was 26,21,5 and 3 respectively.Conclusions A longer duration of extended consolidation therapy after meeting NAs cessation criteria may contribute to the lower relapse rates.

Objective To investigate expression and significance of serum interleukin-32 of patients with chronic hepatitis B (CHB) treated with different anti-viral drugs.Methods One hundred and eighty CHB patients were randomly divided into two groups.The first group included 92 CHB patients,who were orally treated with lamivudine (LAM) 100 mg+ ADV 10 mg,once daily.The second group included 88 CHB patients who were subcutaneously treated with interferon (IFN),180 μg,once a week.The treatment period was 48 weeks.Serum IL-32 expression of patients was tested by ELISA,and the difference in IL-32 expression between two groups was compared by using statistical methods.Then the correlations between IL-32 and alanine aminotranferase (ALT),aspartate aminotranferase (AST),total bilirubin (TBIL),HBV DNA were analyzed,respectively.Results Serum IL-32 expression of all patients gradually decreased after anti-viral treatment,but the difference in IL-32 expression between two groups was not statistically significant until weeks 48.Serum IL-32 expression was positively related with serum ALT,AST and HBV DNA load,respectively,and was not related with serum TBIL.Conclusion Serum IL-32 expression of CHB patients gradually decreased after anti-viral treatment.IL-32 might be involved in the pathogenesis of CHB.

Objective To investigate the expression of chemokine receptors CCR4,CCR6,CXCR3 on Th17 cell,and analyze the correlation between chemokine receptors and serum biochemical parameters of liver function test and hepatitis B virus (HBV) DNA load in peripheral blood of chronic hepatitis B (CHB) patients.Methods Thirty patients with CHB (CHB group) and 15 healthy persons (control group) were enrolled in the study.CCR4,CCR6,CXCR3 expression levels on Th17 cell were assayed by flow cytometry.The correlation between chemokine receptors and alanine aminotransferase (ALT),total bilirubin (TBil),and HBV DNA load were analyzed using Pearson' s correlation analysis,respectively.Results CCR4,CCR6,CXCR3 expression levels on CD4 + Th17 cell in CHB group were higher than that of control group.Moreover,the difference between them was statistically significant (P ＜ 0.05).CCR4,CCR6 expression levels on CD8 + Th17 cell in CHB group were higher than that of control group (P ＜ 0.05).Although CXCR3 expression level on CD8 + Th17 cell in CHB group was higher than that of control group,there was no significant difference between them (P ＞ 0.05).CCR4,CCR6 expression levels were positively correlated with serum ALT,HBV DNA load,respectively (P ＜ 0.05),but were not correlated with TBil (P ＞ 0.05).Conclusion Expression levels of chemokine receptor on Th17 cell were increased in patients with CHB and were positively associated with degree of liver inflammation.Therefore,CCR4,CCR6 expression on Th17 cell might be involved in liver injury resulted from Th17 cell.

Objective To investigate the efficacy of combined treatment of PEG IFNα-2a and recombinant hepatitis B vaccine in CHB patients with HBeAg positive.Methods 75 CHB patients with HBeAg positive were enrolled into this study.45 patients received the monotherapy of pegylated IFNα-2a (group A),and 30 patients were treated with PEG IFNα-2a combined with recombinant hepatitis B vaccine (group B).The two groups were compared clinical features,such as ALT,HBsAg levels and HBeAg seroconversion rates,HBV DNA suppression,at different time point(At 0,24,48,72 week).Results At week 0,levels of aminotransferases,HBsAg and HBV DNA were not statistically significant between the two groups(P ＞0.05).But the level of HBeAg in group B was much more than that in group A.This diversity show statistical significance(P ＜ 0.05).During week 24 to week 48,rates of aminotransferases normalization HBsAg seroconversion HBeAg seroconversion,and HBV DNA suppression were also not statistically significant between group A and B (P ＞ 0.05).At the 72 week of follow up,levels of aminotransferases,HBeAg seroconversion rate and HBsAg levels were not statistically significant among the two groups (P ＞0.05),but the negative conversion rate of HBV DNA drop in group B was much more than that in group A,the difference was statistically significant (P =0.032).Conclusion The combined treatment of PEG IFNα-2a and recombinant hepatitis B vaccine in CHB patients with HBeAg positive can improve the negative conversion rate of HBV DNA 72 weeks after the end of the 48 week of treatment,but wasn't associated with HBeAg seroconversion and HBsAg levels.