Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Correlation Analysis Between HPLC Fingerprint and Anti-inflammatory Activity of Speranskiae Tuberculatae Herba / 中国实验方剂学杂志

Objective: The aim of this study was to investigate high performance liquid chromatography (HPLC) fingerprint,anti-inflammatory activity as well as the correlation between them in Speranskiae Tuberculatae Herba. Method: Fingerprint by HPLC was established on Speranskiae Tuberculatae Herba from different sources. The common peaks were evaluated on the basis of similarity evaluation together with hierarchical cluster analysis (HCA) and principal component analysis (PCA). Ear swelling induced by xylene in mice model was used to study the anti-inflammatory activity. Grey relational analysis (GRA) and partial least square regression analysis (PLSR) were used to study the relationship between the HPLC fingerprint and the anti-inflammatory activity. Result: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established and 24 common peaks were determined,with the similarity above 0.907 (except for S2 and S5). Four peaks were identified by comparing to reference substances. The result of HCA showed that Speranskiae Tuberculatae Herba from different sources were clustered into four categories,in consistent with the result of PCA. Combined with discriminant analysis of partial least squares discrimination analysis (PLS-DA),three signature compounds represented by 5,6,7 peaks were responsible for the differences between groups. Different sources of Speranskiae Tuberculatae Herba differed in anti-inflammatory activity. The sectrum-activity relationship showed that the peaks 1,4,5,6,and 10 were positively correlated with the anti-inflammatory activity. Conclusion: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established,and 5 components closely related to the anti-inflammatory activity were determined. The present study provide more comprehensive reference for quality control of the Speranskiae Tuberculatae Herba.

Factors associated with efficacy of inucleoside analogues on sequential interferon therapy in HBeAg positive chronic hepatitis B patients / 中华实验和临床病毒学杂志

Objective@#To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg positive chronic hepatitis B (CHB) patients.@*Method@#HBeAg positive CHB patients treated with nucleoside analogue (NA) treatment received PEG-IFN α-2a 180 μg subcutaneously once weekly.NA was continually used with PEG-IFNα-2a during the first 12 weeks. HBsAg/HBeAg level and HBV DNA load were observed in the sequential pre-treatment (baseline) period, 12 th, 24 th, 36 th, 48 th and 72 nd weeks of sequential therapy in all patients.@*Result@#Of the 56 HBeAg-positive CHB patients, 5 (23.1%) achieved HBsAg loss/seroconversion, the baseline HBsAg level in HBsAg loss/seroconversion group was lower than that of the patients in the group that did not achieve HBsAg loss/seroconversion (2.750 lg IU/ml vs. 3.699 lg IU/ml, t=0.955, P=0.000); the difference was statistically significant in HBsAg decreased at the 12 th, 24 th, 36 th, 48 th week in the course of sequential therapy (0.913 vs 0.149, 2.847 vs 0.189, 4.378 vs 0.248, 4.587 vs 0.274 lg IU/ml) (t=-2.950, P=0.040; t=-8.732, P=0.009; t=-8.483, P=0.001; t=-8.214, P=0.003); 11(19.6%) achieved HBeAg loss/ seroconversion, the HBeAg baseline level in HBeAg loss/seroconversion group was lower than the patients in the group that not achieved HBeAg loss/seroconversion (1.217 lgS/CO vs 1.884 lgS/CO, t=2.061, P=0.044); the difference was statistically significant in HBsAg, HBeAg decreased at 24 th, 36 th, 48 th week in the course of sequential therapy between the two groups (1.330 vs 0.205, 2.084 vs 0.258, 1.972 vs 0.284, lg IU/ml; 1.168 vs 0.455, 1.363 vs 0.461, 1.177 vs 0.447, lg S/CO) (t=2.238, P=0.049; t=2.619, P=0.025; t=2.278, P=0.048); (t=2.273, P=0.043; t=3.415, P=0.001; t=2.271, P=0.049).@*Conclusions@#To HBeAg-positive CHB, lower baseline HBsAg, HBeAg level and HBsAg, HBeAg decreased earlier were could predict easier achievement of HBs(e)Ag loss/seroconversion.

Changes of APRI score in HBeAg-negative treatment-naive chronic hepatitis B patients receiving 3 year entecavir therapy / 中华实验和临床病毒学杂志

Objective@#We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy.@*Methods@#Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment.@*Results@#All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05).@*Conclusions@#APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B / 中华医学杂志(英文版)

Background@#Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).@*Methods@#Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.@*Results@#IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively).@*Conclusions@#IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

Factors associated with efficacy of nucleos(t)ide analogues with sequential interferon therapy in HBeAg negative chronic hepatitis B patients / 中华实验和临床病毒学杂志

Objective@#To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg negative chronic hepatitis B (CHB) patients.@*Methods@#HBeAg negative CHB patients with NA treatment received PEG-IFNα 2a 180 μg subcutaneously once weekly. NA was continually used with PEG-IFN 2a during the first 12 weeks. HBsAg level and HBV DNA load were observed in the sequential pre-treatment (baseline), 12th, 24th, 36th, 48th, 72nd and 96th weeks of sequential therapy in all patients.@*Results@#Of the 26 HBeAg negative CHB patients, 6 (23.1%) achieved HBsAg loss/seroconversion. The comparison between HBsAg loss/ seroconversion group and the group not achieved HBsAg loss/ seroconversion showed that the baseline HBsAg level in HBsAg loss/seroconversion group was 2.210 log10IU/ml, was lower than (t=-4.252, P=0.000) HBsAg-positive patients (3.385 log10IU/ml) in the groupp that not achieved HBsAg loss/seroconversion, the difference was statistically significant in HBsAg decreased at 72nd, 96th week in the course of sequential therapy (3.511 vs. 0.723log10IU/ml, 4.291 vs. 0.737 log10IU/ml) (t=6.712, P=0.000, t=13.319; P=0.000, 0.00); the difference was not statistically significant in age, gender and NA therapy time between the two groups; 12 (46.2%) of patients achieved sustained virologic response (SVR), the baseline of HBsAg level was 2.575 log10IU/ml, was less than (t=-4.319, P=0.000) the patients who did not achieve SVR (3.576 log10IU/ml), the difference was statistically significant in HBsAg decrease of each time in the course of sequential therapy between the two groups (0.612 vs. 0.088, 1.192 vs. 0.107, 1.566 vs. 0.167, 1.817 vs. 0.176, 2.424 vs. 0.193, 2.188 vs. 0.014, log10IU/ml) (t=3.109, 4.717, 4.500, 4.544, 5.560, 4.265, P=0.008, 0.010, 0.001, 0.001, 0.000, 0.003), the difference was not statistically significant in gender and NA therapy time, the difference was statistically significant in age (30.8 vs. 39.9 years) ( t=-2.219, P=0.038). Of 9 CHB patients whose baseline HBV DNA were positive, 5 patients (55.6%) had HBV DNA loss after sequential treatment, the patients whose HBV DNA loss with HBsAg decreased at 12th week in the course of sequential therapy, but there was no influence in the HBsAg decrease/loss after 12th week, the difference was not statistically significant in age, gender, NA therapy time, HBsAg and HBsAg decrease in the course of sequential therapy between HBV DNA-negative and HBV DNA-positive groups.@*Conclusions@#To HBeAg-negative CHB, patients with low baseline HBsAg (2 log10 IU/ml level) and significantly lower HBsAg decrease early were more likely to receive SVR. Among them, prolonged interferon therapy is easier to achieve HBsAg loss/seroconversion.

Re-treatment with peginterferon-ribavirin and direct antiviral agents of patients with chronic hepatitis C after failure of intensified treatment / 中华实验和临床病毒学杂志

Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Plasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.</p><p><b>METHODS</b>The healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.</p><p><b>RESULTS</b>In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).</p><p><b>CONCLUSIONS</b>This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.</p>

Changes in peripheral blood during the antiviral treatment with Peg-IFNα-2 a and ribavirin for patients with chronic hepatitis C and the relationship between the changes and effect / 中华实验和临床病毒学杂志

Objective@#To observe the changes of peripheral blood image of chronic hepatitis C (CHC) patients treated with pegylated interferon (Peg-IFN) and ribavirin, and explore the relationship between the changes and serum virological respose (SVR).@*Methods@#Patients with CHC treated with Peg-IFN α-2 a and ribavirin in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for peripheral blood cells routine examination and Liver function, kidney function, thyroid function at baseline and week 2, 4, 8, 12, 24, 36, 48, and week 12, 24, 48 after the end of treatment for chronic hepatitis C, and HCV RNA.@*Results@#The decrease of peripheral blood cell counts began to appear at week 2 of treatment. For CHC patients without cirrhosis, white blood cells, lymphocyte, hemoglobin and platelets at week 2, while minimum values were seen at week 36, and the neutrophils reached the minimum value to at week 24. Significant recovery of the peripheral blood changes was seen at the end of treatment (48 weeks), and reached pre-treatment levels at week 48 after the end of treatment. For CHC patients with cirrhosis, white blood cells, lymphocytes, hemoglobin and platelets significantly decreased at week 2, while neutrophils reached a minimum value at 2 weeks. And hemoglobin and platelets reached a minimum value at 24 weeks, and the white blood cells reached the minimum value at weeks 24-36 besides lymphocyte reached the minimum value at week 36. Significant recovery was seen at the end of treatment (48 weeks), and the blood cell counts reached pre-treatment levels at 48 weeks after the end of treatment. For patients with CHC, hemoglobin decreased by more than 27.47% at week 4, which means that the patient would have a predictive significance for SVR, as well as the of PLT reduction by more than 36.96% at week 8.@*Conclusions@#During the treatment with Peg-interferon and ribavirin, the variation of blood picture has some predicting effect, which predicts the result of antiviral treatment.

Changes of peripheral blood during the antiviral treatment with Peg-IFNα-2 a for patients with chronic hepatitis B and the relationship between the changes and effect / 中华实验和临床病毒学杂志

Objective@#To observe the changes of peripheral blood picture of CHB with Peg-IFN, and explored the relationship between the changes and decline of HBV DNA, clearance of HBsAg.@*Methods@#Patients with CHB treated with Peg-IFN α-2 a in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for blood routine examination and Liver function, kidney function, thyroid function of baseline and weeks 2, 4, 8, 12, 24, 36, 48, and weeks 12, 24, and 48 after the end of treatment for chronic hepatitis B, and HBV DNA, HBsAg.@*Results@#The decrease of peripheral blood cells began to occur at week 2 of treatment. For CHB with HBeAg negative patients, white blood cells, lymphocyte, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value occurred at 48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48 weeks after the end of treatment. For CHB with HBeAg positive patients, white blood cells, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value was found at 36-48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48weeks after the end of treatment. For patients with CHB, hemoglobin declined by more than13.64% at 36th week, which means that the patient would have a predictive significance for decrease of HBV DNA, and drops of more than 0.33% at 2nd week means that the patient would have a predictive significance for clearance of HBsAg.@*Conclusions@#During the treatment with interferon, the variation regularity of blood picture for predicting result have a certain effect, which may help predict and monitor the change of blood picture in clinical work.

Protectivity of hepatitis B surface antibody in children between 1 and 3 years after successful blocking of mother-to-child transmission / 中华实验和临床病毒学杂志

Objective@#To investigate the change of hepatitis B surface antibody (HBsAb) titer and its long-term protection and infection rates between 1 and 3-year-old children whose mothers were chronic hepatitis B pregnant woman with HBeAg positive and high viral load after successful blocking of mother-to-child transmission.@*Methods@#One-year-old children whose mothers were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA≥106IU/ml were enrolled, then were followed up till 3 years old, and tested the five serological markers of hepatitis B and biochemical parameters at the age of one and three years respectively, and analyzed HBsAb titer, positive rate, negative rate and infection rate of 1 to 3-year-old children without enhanced vaccination; meanwhile, data of HBsAb titers at the age of 7 months were collected HBsAb titer, positive rate, and negative rate were analyzed.@*Results@#Totally 264 1-year-old children were enrolled into the study, including 178 children without enhanced vaccination between seven months and 1 year of age, and 114 children without enhanced vaccination between 1 year and 3 years of age. Our result showed that there were no infected children at the age between 1 and 3 years. HBsAb titer decreased from 7 months to 1 year old and dropped from 1 000 IU/L to 509.43 IU/L (P<0.05), and the antibody was still protective. From 1 year to 3 years old, HBsAb titer dropped from 466.72 IU/L to 67.3 IU/L (P< 0.05); at the age of 3 years, 60.52 % children were either weakly positive or negative, but still protective, but significantly less than those who had the reinforced vaccination. As a result , the children without the enhanced vaccination between 1 and 3 years of age were still at high risk.@*Conclusions@#If the antibody was protective at 7 months, children were not easily infected between 1 year and 3 years of age. At the age of 3, the antibody dropped to low or no responsive levels, and the children were still at high risk. It is necessary to take protective measures and supplement the vaccine.

Negative Correlation of Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Levels with the Severity of Liver Inflammation in Treatment-naïve Patients with Chronic Hepatitis B Virus Infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Estimating the grades of liver inflammation is critical in the determination of antiviral therapy in patients chronically infected with hepatitis B virus (HBV). The aim of this study was to investigate the correlation of serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) with the liver inflammation grades in treatment-naïve patients with chronic HBV infection.</p><p><b>METHODS</b>We retrospectively enrolled 584 treatment-naïve HBeAg-positive patients who underwent liver biopsy in Ditan Hospital from January 2008 to January 2016. Based on the severity of liver inflammation, the patients were divided into minimal, mild, and moderate groups. SPSS software was used for statistical analysis of all relevant data.</p><p><b>RESULTS</b>The liver histological examinations showed that 324, 194, and 66 patients had minimal, mild, and moderate liver inflammation, respectively. The median age of the three groups was 30, 33, and 38 years, respectively (Χ2 = 26.00, P < 0.001). The median HBsAg levels in minimal, mild, and moderate inflammation groups were 4.40, 4.16, and 3.67 log U/ml, respectively, and the median HBeAg levels in the three groups were 3.12, 2.99, and 1.86 log sample/cutoff, respectively; both antigens tended to decrease as the grade of inflammation increased (Χ2 = 99.68 and Χ2 = 99.23, respectively; both P < 0.001). The cutoff values of receiver operating characteristic curve in the age, HBsAg and HBeAg levels were 36 years, 4.31 log U/ml, and 2.86 log S/CO, respectively, l to distinguish minimal grade and other grades of treatment-naïve HBeAg-positive patients with chronic HBV infection.</p><p><b>CONCLUSIONS</b>Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values might help us to distinguish minimal grades and other grades and detect those who do not need antiviral therapy in treatment-naïve HBeAg-positive patients with chronic HBV infection.</p>

Ratios of T-helper 2 Cells to T-helper 1 Cells and Cytokine Levels in Patients with Hepatitis B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases.</p><p><b>METHODS</b>Thirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study. Th cell proportions in peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen were detected.</p><p><b>RESULTS</b>The Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including IT, IC, and AHB groups) were significantly different from those in HI group (24.10% ± 8.66% and 1.72 ± 0.61 vs. 15.16% ± 4.34% and 2.40 ± 0.74, respectively; all P < 0.001). However, there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-γ, and interleukin (IL)-17A were significantly lower than those in HI group (29.26 pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96 pg/ml, respectively; all P < 0.05). IFN-α2, IL-10, and transforming growth factor (TGF)-β2 median levels in hepatitis group (including patients in AHB and IC groups) were significantly higher than those in IT group (40.14 pg/ml, 13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml, respectively; all P < 0.05), while patients in hepatitis group had significant lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared with IC group, patients in AHB group had significant higher median levels of IL-10, TGF-β1, and TGF-β2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs. 8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05).</p><p><b>CONCLUSIONS</b>Compared with chronic HBV-infected patients in immune-tolerance phase, chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th1 ratios, significantly higher levels of IFN-α2, IL-10, and TGF-β. AHB patients had significantly higher IL-10 and TGF-β levels than chronic HBV-infected patients in immune-active phase.</p>

Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a.</p><p><b>METHODS</b>A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months.</p><p><b>RESULTS</b>Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss.</p><p><b>CONCLUSIONS</b>Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.</p>

Efficacy of pegylated-interferon alpha-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy.</p><p><b>METHODS</b>Patients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software.</p><p><b>RESULTS</b>A total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%.</p><p><b>CONCLUSION</b>Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.</p>

Study on the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011.</p><p><b>METHODS</b>We summed up the changes in the characteristics of the etiology of acute hepatitis of patients mentioned above, and preliminarily analyze the causes.</p><p><b>RESULTS</b>From 2002 to 2011, 6235 patients with acute hepatitis were admitted to Ditan Hospital, aged between 12 and 78 years old, Of which 4309 were male and 1926 female. Acute viral hepatitis accounted for 70.44%-85.07%, while CMV, EBV, drug-induced liver injury accounted less than 5%, and acute hepatitis D and acute hepatitis C less than 1.10%. From year to year, the incidence and constitution of acute hepatitis changed significantly. The proportion of patients with acute hepatitis in total hospitalized patients was from 20. 38% to 2.05%. In 10 years, the percentage of acute hepatitis A decreased most obviously, about 99.11%, while 45.07% decline in incidence of acute hepatitis B and 62. 28% of acute hepatitis E. The constituent ratio of acute hepatitis also changed significantly. The proportion of acute hepatitis A declined from 31.31% in 2002, to less than 1% in 2011. The proportion of acute hepatitis B increased from 26.47% in 2002 to 45.88% in 2011, an increase of about 2 folds in 10 years. The proportion of acute hepatitis E increased from 26.73% in 2002 to 32.05% in 2010, a rise of 1.20 times in 10 years.</p><p><b>CONCLUSIONS</b>The proportion of patients with acute hepatitis in total hospitalized patients decreased from 20. 38% in 2002 to 2. 05% in 2011 in Beijing Ditan Hospital. The constituent ratio of acute hepatitis changed, too.</p>

Analyse related factors of impact and prognosis of 73 cases of severe hepatitis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>A retrospective study was conducted to investigate the clinical features and prognostic factors of 73 cases of severe hepatitis.</p><p><b>METHODS</b>To summarize clinical features of 73 cases of severe hepatitis, grouping by etiology and pathogenesis. A retrospective analysis was performed to evaluate the relationship between biochemical characteristics (liver function, renal function, electrolytes, PTA, etc) and complications (hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, ascites, abdominal infections, etc) and prognosis.</p><p><b>RESULTS</b>(1) HBV infection alone accounted for 65.75%. Alcoholic liver disease, drug-induced liver injury, hepatitis E, autoimmune hepatitis, overlapping causes and other factors were five cases (6.85%), six cases (8.22%), two cases (2.74%), two cases (2.74%), seven cases (9.59%) and three cases (4.11%) respectively. According to the incidence rate, severity and underlying liver condition, subacute hepatitis, cases based on chronic hepatitis and on cirrhosis were 12 cases (16.43%), 11 cases (15.07%), 50 cases (68.49%) respectively. Clinical manifestations with or without hepatic encephalopathy accounted for 58.90% or 41.10%. (2) The highest mortality of severe hepatitis was alcoholic liver disease and patients on the basis of overlapping factors (66.67%), followed by autoimmune liver disease (50%). The mortality of HBV-related hepatitis was 18.75%. Overall mortality of 73 cases of severe hepatitis was 28.77%, of which cirrhosis group was higher than non-cirrhotic group (40% vs 4.3%, P = 0.002). The difference was statistically significant. Patients without hepatic encephalopathy had lower mortality than with hepatic encephalopathy (3.33% vs 46.51%). The mortality of patients with hepatic encephalopathy Stage III and IV was 72.73%. (3) Independent samples t test filtered nine factors associated with death, namely cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, serum creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB) and serum sodium. The results of multivariate conditional logistic regression analysis indicated that hepatic encephalopathy, serum creatinine levels were risk factors for death, whereas ALB as a protective factor.</p><p><b>CONCLUSION</b>Hepatic encephalopathy, serum creatinine levels were risk factors for severe hepatitis death, But ALB was protective factor. Nucleotide analogs using was the main reason why the mortality of hepatitis B was as low as 18.75%.</p>

Study on retreatment of CHC patients with initial treatment failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the retreatment of CHC patients with initial treatment failure and how to achieve SVR.</p><p><b>METHODS</b>54 patients who had experienced treatment failure were enrolled and retreated with standard treatment of pegylated interferon and ribavirin or intensive treatment, respectively. Their SVR rates were statistically compared, to decide two therapies' application.</p><p><b>RESULTS</b>54 patients had been retreated, and total SVR rate was up to 75.92%, with 88.46% in relapsed patients and 64.29% in non-responders. After retreatment with pegylated interferon and ribavirin, SVR rate was 95.45% in patients with prior interferon monotherapy, and 64.71% in patients with prior interferon and ribavirin, and 60% in patients with prior pegylated interferon alpha-2a monotherapy. SVR rate of relapsed patients was significantly higher than that of non-responders.</p><p><b>CONCLUSIONS</b>In CHC patients with treatment failure, SVR rate of retreatment with standard treatment or intensive treatment still can be up to 60%-90%. Retreatment with standard therapy can be applied to patients who had received interferon monotherapy or interferon plus ribavirin. Three types of patients who need intensive retreatment were as following: patients nonresponsive to interferon plus ribavirin or pegylated interferon alpha-2a monotherapy, and patients with treatment failure who had received prior standard treatment.</p>

Study on effect of intensive treatment for refractory chronic hepatitis C patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the effect of intensive treatment for refractory chronic hepatitis C, and to improve the sustained viral response (SVR) rate of treatment with interferon plus ribavirin by optimizing therapeutic dose and course.</p><p><b>METHODS</b>Patients who did not acquire response or partial response by standard therapy (PEG-IFN alpha subcutaneous injection weekly plus Ribavirin 10.5 mg/kg) every day were enrolled and retreated with intensive treatment of 10 MU interferon every other day or 360 microg pegylated interferon alpha-2a weekly according to patients' wishes, and ribavirin 15 mg/kg every day. Serum HCV RNA was detected at baseline,treatment week 4, 12 and every 12 weeks succedent and 24 weeks after treatment end. Course of treatment was 72 to 96 weeks according to viral response. SVR was the mark of therapeutic effect.</p><p><b>RESULTS</b>18 patients completed whole range therapy and follow-up, in which 12 patients acquired SVR, 5 patients treatment failure and 1 relapse. 3 patients acquired rapid viral response (RVR), and they all got complete Early Viral Response (cEVR) and SVR. RVR Patients' viral loads were significantly lower than that of patients who did not acquire RVR (t = 4. 687, P < 0.001). In 15 patients who did not acquire RVR, 8 patients acquired cEVR, and 9 acquired SVR. SVR rate of patients who were administered PEG-IFN alpha-2a was 4/5, 11 patients who acquired cEVR all acquired SVR, while in 7 patients who did not acquire cEVR, only 1 patient acquired SVR.</p><p><b>CONCLUSIONS</b>High percent patients, who did not acquire response or partial response by previous standard antiviral therapy, could gain SVR by intensive dose interferon plus Ribavirin. In intensive treatment procedure, adjusting and prolonging course according to viral response after HCV RNA turned negative were important measures to improve refractory Chronic Hepatitis C SVR rate.</p>

Comparison of dose distribution in gamma knife radiotherapy plan, conformal radiotherapy plan and intensity modulated radiotherapy plan for patients with small mass in lung / 中华放射肿瘤学杂志

Objective To compare dose distribution in gamma knife radiotherapy plan, conformal radiotherapy(CRT)plan and intensity modulated radiotherapy(MRT)plan for patients with small mass in lung, and evaluate their characters. Methods Fourteen patients with small mass in lung participated in the study. Gamma knife radiotherapy plan(plan 1), CRT plan(plan 2)and IMRT plan(plan 3)were made for each mass. The planning target volume(PTV)and the dose include 95% PTV were consistent.Conformal index(CI), homogeneity index(HI), lung V5 ,V10 ,V20 ,V30 and the max dose of esophagus and spinal cord were analyzed. Paired samples t-test was used for comparison between each two plans. Results The CI of the plan 1,2 and 3 were 0. 58,0. 46 and 0. 63, respectively. CI of the plan 1 ＞ that of the plan 2 (t= -3.95,P =0.000),plan 3 ＞ plan 2(t = -6.01 ,P =0.000),plan 1 =plan 3(t =1.64,P =0.116);HI of the plan 1,2 and 3 were 1.66,1.10 and 1.07 respectively. HI of the plan 1 ＞ plan 2 ,plan 1 ＞ plan 3(t= -20.52,21.41 respectively, both P=0. 000),plan 2 = plan 3(t= -1.08,P=0.294). The wholelung V5 ,V10 ,V20 and V30 were 10.0% ,5.6% ,2. 4% and 1.2%, respectively, in plan 1 ;20. 2% ,13. 4%,6. 9% ,3.0%, respectively, in plan 3; and 26. 5%, 18. 0%, 11.4% and 4. 6%, respectively, in plan 2.The V5, V10, V20 and V 30 of the plan 1 ＜ in plan 2(t = 9. 68,8. 41,5. 45,5. 14, all P = 0. 000), the V5,V10,V20 and V30 of the plan 1 ＜ in plan 3(t=7.58,8.95,6. 15,4.78, respectively, all P=0.000),the V5 ,V10, V20andV30 oftheplan2 ＞ inplan3(t =9. 71,5. 91,4. 13,3.91, respectively, allP =0.000).The max dose of esophagus in plan 1 ,2 and 3 were 24.93 ± 21.54, 31.90 ± 18. 75, 29. 19 ± 23.09 Gy,respectively, plan 1 ＜ plan 2(t = -2. 71 ,P=0.013),plan 1 = plan 3(t = - 1.49,P =0. 152),plan 2 =plan 3(t = 1.35, P = 0. 193). The max dose of spinal cord in plan 1,2 and 3 were 12.07 ± 10. 67,17.70 ±11.35 and 8.92 :± 10. 04 Gy, respectively, plan 2 ＞ plan 1 ＞plan 3(t = -2. 38,2. 29,4. 83,P=0. 1027,0.033,0.000);All three plans of each mass meet the needs that the max dose of the esophagus≤60 Gy and the max dose of spinal cord ≤40 Gy. Conclusions The dose of the normal lung was lower, but the HI and the max dose of spinal cord were higher in Gamma knife radiotherapy plan than those in the CRT and the IMRT plan of the small mass in lung.