AIM: To characterize the IFN-response and its modul- ation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of ...AIM: To characterize the IFN-response and its modul- ation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-a2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes (ISGs). In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS: Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and 6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes (IFITM1, 6-16), the response to IFN-a could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Stat1 activation and ISGF3 formation after stimulation with IFN-a in HepG2.2.15 compared to HepG2 cells. CONCLUSION: These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expression by reducing HBV gene expression and replication.展开更多
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To ...BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.展开更多
AIM: To explore the effect of He Jie Tang (decoction for medication) on serum levels of T lymphocyte subsets, NK cell activity and cytokines in chronic hepatitis B patients.METHODS: Eighty-five patients with chronic h...AIM: To explore the effect of He Jie Tang (decoction for medication) on serum levels of T lymphocyte subsets, NK cell activity and cytokines in chronic hepatitis B patients.METHODS: Eighty-five patients with chronic hepatitis B were divided randomly into two groups. Fifty patients in group Ⅰ were treated with He Jie Tang (HJT) and 35 patients in group Ⅱ were treated with combined medication. The levels of T-lymphocyte subsets (CD3+,CD4+, CD8+), NK cell activity, cytokines (TNF-α, IL-8,sIL-2R) were observed before and after the treatment.Another 20 normal persons served as group 3.RESULTS: The level of CD4+ cells and NK cell activity were lower, whereas the level of CD8+ cells in patients was higher than that in normal persons (t = 2.685,3.172, and 2.754 respectively; P＜0.01). The levels of TNF-α, IL-8, and sIL-2R in chronic hepatitis B patients were higher than those in normal persons (t = 3.526,3.170, and 2.876 respectively; P＜0.01). After 6 months of treatment, ALT, AST, and TB levels in the two groups were obviously decreased (t = 3.421, 3.106, and 2.857respectively; P＜0.01). The level of CD4+ cells and NK cell activity were increased whereas the level of CD8+ cells decreased (t = 2.179, 2.423, and 2.677 respectively;P＜0.05) in group I. The levels of TNF-α, IL-8, and sIL-2R in group Ⅰ were decreased significantly after the treatment (t = 2.611, 2.275, and 2.480 respectively;P＜0.05) but had no significant difference in group Ⅱ after the treatment (t = 1.906, 1.833, and 2.029respectively; P＞0.05). The total effective rate had no significant difference between the two groups (x2 = 2.882,P＞0.05) but the markedly effective rate wass ignificantly different between the two groups (x2 = 5.340, P＜0.05).CONCLUSION: HJT is effective in treating chronic hepatitis B. HJT seems to exert its effect by improving the cellular immune function and decreasing inflammatory cytokines in chronic hepatitis B patients.The function of HJT in protecting liver function in the process of eliminating virus needs to be further studied.展开更多
基金Supported by grants from the Deutsche Forschungsgemeinschaft (DFG SCHL 377/2-2, LU 669/2-1 and GRK 1045/1)
文摘AIM: To characterize the IFN-response and its modul- ation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-a2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes (ISGs). In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS: Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and 6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes (IFITM1, 6-16), the response to IFN-a could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Stat1 activation and ISGF3 formation after stimulation with IFN-a in HepG2.2.15 compared to HepG2 cells. CONCLUSION: These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expression by reducing HBV gene expression and replication.
基金Supported by the Class A Project of the Key Research and Development Programs of the Science and Technology Department of Anhui Province,No.1804h08020236the Key Project of the Natural Science Foundation of Anhui Province,No.KJ2018A0206
文摘BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.
基金Supported by the Administrative Bureau of TCM and Chinese Drugs of Guangdong Province, No. 98374 and No. 100108
文摘AIM: To explore the effect of He Jie Tang (decoction for medication) on serum levels of T lymphocyte subsets, NK cell activity and cytokines in chronic hepatitis B patients.METHODS: Eighty-five patients with chronic hepatitis B were divided randomly into two groups. Fifty patients in group Ⅰ were treated with He Jie Tang (HJT) and 35 patients in group Ⅱ were treated with combined medication. The levels of T-lymphocyte subsets (CD3+,CD4+, CD8+), NK cell activity, cytokines (TNF-α, IL-8,sIL-2R) were observed before and after the treatment.Another 20 normal persons served as group 3.RESULTS: The level of CD4+ cells and NK cell activity were lower, whereas the level of CD8+ cells in patients was higher than that in normal persons (t = 2.685,3.172, and 2.754 respectively; P＜0.01). The levels of TNF-α, IL-8, and sIL-2R in chronic hepatitis B patients were higher than those in normal persons (t = 3.526,3.170, and 2.876 respectively; P＜0.01). After 6 months of treatment, ALT, AST, and TB levels in the two groups were obviously decreased (t = 3.421, 3.106, and 2.857respectively; P＜0.01). The level of CD4+ cells and NK cell activity were increased whereas the level of CD8+ cells decreased (t = 2.179, 2.423, and 2.677 respectively;P＜0.05) in group I. The levels of TNF-α, IL-8, and sIL-2R in group Ⅰ were decreased significantly after the treatment (t = 2.611, 2.275, and 2.480 respectively;P＜0.05) but had no significant difference in group Ⅱ after the treatment (t = 1.906, 1.833, and 2.029respectively; P＞0.05). The total effective rate had no significant difference between the two groups (x2 = 2.882,P＞0.05) but the markedly effective rate wass ignificantly different between the two groups (x2 = 5.340, P＜0.05).CONCLUSION: HJT is effective in treating chronic hepatitis B. HJT seems to exert its effect by improving the cellular immune function and decreasing inflammatory cytokines in chronic hepatitis B patients.The function of HJT in protecting liver function in the process of eliminating virus needs to be further studied.
