Prediction for HBsAg seroconversion in children with chronic hepatitis B.

BACKGROUND: To establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy. METHODS: A total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion. RESULTS: The 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log10 copies/106 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146). CONCLUSIONS: HBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources.

IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C.

Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m2 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×105 IU/ml) and higher baseline viral load group(≥6×105 IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.

[Changes of alveolar macrophage phagocytosis and TNF-alpha, IL-6 of rats with Pneumocystis pneumonia].

OBJECTIVE: To observe the changes of alveolar macrophage (AM) phagocytosis and the levels of TNF-alpha and IL-6 in AM supernatants and bronchoalveolar lavage fluid (BALF) of rats with Pneumocystis pneumonia (PCP). METHODS: Wistar rats were injected with dexamethasone intramuscularly and continually to establish the model of PCP, the AM phagocytosis and levels of TNF-alpha and IL-6 in AM supernatants and BALF of rats with PCP were detected, meanwhile, the normal controls were set. RESULTS: The phagocyting percentage [(20.61 +/- 2.04)%] and phagocyting index (0.25 +/- 0.21) of the PCP group were significantly lower than those [(25.45 +/- 3.1)% and (0.31 +/- 0.16)] of the control group (P < 0.05), TNF-alpha (16.84 +/- 0.86) pg/ml and IL-6 (1.05 +/- 0.19) pg/ml in BALF of the PCP group were significantly higher than those [(12.48 +/- 0.84) pg/ml and (0.86 +/- 0.11) pg/ml] of the control group (P < 0.05), but there were no significant differences for the levels of TNF-alpha and IL-6 in AM supernatants between the two groups (P > 0.05). CONCLUSION: AM phagocytosis reduces evidently of PCP rats, but the levels of TNF-alpha and IL-6 in BALF rise evidently.

[Apoptosis of human leukemia K562 cell in vitro induced by Toxoplasma gondii].

OBJECTIVE: To investigate whether the Toxoplasma gondii can inhibit proliferation of human leukemia K562 cells and/or induce apoptosis of the cells in vitro. Methods K562 cells (5x10(4)/ml) were harvested at mid-exponential phase and planted in 96 well plates with 100 microl each and in 50 ml culture bottles, 1.5 ml each. The cells were treated for 48 hours with different concentration of Toxoplasma tachyzoites. Growth inhibition rate was measured with MTT method. Apoptosis was detected through following ways: fluorescence microscopy with Hoechst 33 258 staining was used for observing the change of cell morphology, agarose electrophoresis was used to detect the DNA changes and FCM was used to observe sub-diploid. RESULTS: Toxoplasma can inhibit proliferation of K562 cells. K562 cells treated with Toxoplasma presented an inhibition rate of 17%, 28%, 48%, 50% and 55% under the tachyzoite concentration of lxl0(4), 2x10(4), 4x 10(4), 8x10(4) and 16xl0(4)/ml respectively, with a significant difference to the control (t=3.606, 5.918, P<0.05; t=9.171, 7.841 and 7.067, P<0.01). Cell contraction and apoptotic bodies were observed under fluorescence microscope. DNA fragment was shown through agarose electrophoresis. Flow cytometric analysis showed an apoptosis peak at 48h. The apoptosis rate was 5.53%, 7.12%, 10.34%, 21.14% and 29.68% respectively. CONCLUSION: Toxoplasma gondii inhibits proliferation and induces cell apoptosis in K562 cells in vitro.