Background： Cytokines play an important role in occorrence and recovery of hepatitis B virus （HBV） infection. The aim of this study was to investigate the changes ofcytokines concentration and its correlation to al...Background： Cytokines play an important role in occorrence and recovery of hepatitis B virus （HBV） infection. The aim of this study was to investigate the changes ofcytokines 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. Tile 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 I FN-ct2, IL-10, and TGF-[31 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-ct2 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 CH B 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. I 0, 18.00] pg/ml） slightly increased （X^2 = 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 （X^2=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.展开更多
Background： 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 functio...Background： 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 ofpDC and serum cytokine network profiles in patients with acute or chronic HBV infection. Methods： 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 ofpDC were tested by flow cytometer. The quantitative determinations ofcytokines, including Fins-like tyrosine kinase 3 ligand （FIt-3L）, interferon （1FN）-α2, IFN-γ, interleukin （IL）-17A, IL-6, IL-10, transforming growth factor （TGF）-β1 and TGF-β2, were performed using Luminex multiplex technology. Results： 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 ofpDC （4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P 〈 0.001）. The counts of CD86 molecular expressed on the surface of pDC in CriB 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 FIt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased （P =0.012） in CH B group. The contents of IL-10, TGF-{31, and TGF-132 in AHB group were significantly increased compared with IT and CHB groups （all P 〈 0.05）. Conclusions： 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 H BV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.展开更多
Background： Estimating the grades of liver inflammation is critical in the determination ofantiviral therapy in patients chronically infected with hepatitis B virus （HBV）. The aim of this study was to investigate t...Background： Estimating the grades of liver inflammation is critical in the determination ofantiviral therapy in patients chronically infected with hepatitis B virus （HBV）. The aim of this study was to investigate the correlation ofserum levels of hepatitis B surface antigen （HBsAg） and hepatitis B e antigen （HBeAg） with the liver inflammation grades in treatment-naTve patients with chronic HBV infection. Methods： We retrospectively enrolled 584 treatment-na＇l＇ve 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 lbr statistical analysis of all relevant data. Results： 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 （X2 =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 （X2 = 99.68 and X2 =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 Iog S/CO, respectively, 1 to distinguish minimal grade and other grades of treatment-naTve HBeAg-positive patients with chronic HBV infection. Conclusions： Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values rnight help us to distinguish rninimal grades and other grades and detect those who do not need antiviral therapy in treatment-naive HBeAg-positive patients with chronic HBV infection.展开更多
基金The work was supported by grants from the Basic and Clinical Fund of Capital Medical University （No. 17JL88） and National Natural Science Foundation of China （No. 81071344）.
文摘Background： Cytokines play an important role in occorrence and recovery of hepatitis B virus （HBV） infection. The aim of this study was to investigate the changes ofcytokines 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. Tile 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 I FN-ct2, IL-10, and TGF-[31 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-ct2 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 CH B 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. I 0, 18.00] pg/ml） slightly increased （X^2 = 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 （X^2=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.
基金The work was supported by grants from the Basic and Clinical Fund of Capital Medical University （No. 17JL88） andNational Natural Science Foundation of China （No. 81071344）.
文摘Background： 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 ofpDC and serum cytokine network profiles in patients with acute or chronic HBV infection. Methods： 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 ofpDC were tested by flow cytometer. The quantitative determinations ofcytokines, including Fins-like tyrosine kinase 3 ligand （FIt-3L）, interferon （1FN）-α2, IFN-γ, interleukin （IL）-17A, IL-6, IL-10, transforming growth factor （TGF）-β1 and TGF-β2, were performed using Luminex multiplex technology. Results： 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 ofpDC （4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P 〈 0.001）. The counts of CD86 molecular expressed on the surface of pDC in CriB 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 FIt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased （P =0.012） in CH B group. The contents of IL-10, TGF-{31, and TGF-132 in AHB group were significantly increased compared with IT and CHB groups （all P 〈 0.05）. Conclusions： 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 H BV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.
文摘Background： Estimating the grades of liver inflammation is critical in the determination ofantiviral therapy in patients chronically infected with hepatitis B virus （HBV）. The aim of this study was to investigate the correlation ofserum levels of hepatitis B surface antigen （HBsAg） and hepatitis B e antigen （HBeAg） with the liver inflammation grades in treatment-naTve patients with chronic HBV infection. Methods： We retrospectively enrolled 584 treatment-na＇l＇ve 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 lbr statistical analysis of all relevant data. Results： 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 （X2 =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 （X2 = 99.68 and X2 =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 Iog S/CO, respectively, 1 to distinguish minimal grade and other grades of treatment-naTve HBeAg-positive patients with chronic HBV infection. Conclusions： Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values rnight help us to distinguish rninimal grades and other grades and detect those who do not need antiviral therapy in treatment-naive HBeAg-positive patients with chronic HBV infection.
