AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic h...AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.展开更多
The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin an...The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin and VNTR genes into VR1012,respectively.The eukaryotic vector pEGFP expressing survivin and MUC1 VNTRs fusion gene pEGFP-MS was also constructed.Mouse melanoma cell line（B16） stably expressing survivin and MUC1 VNTRs（MS ＋ B16） was established by Lipofectamine-mediated transfection of pEGFP-MS into B16 cells.EGFP expression in MS ＋ B16 cells was observed using a fluorescent microscope and survivin and MUC1 VNTRs（MS） expression was confirmed by means of Western blot analysis.A syngenic graft tumor model was generated by subcutaneous injection of MS ＋ B16 cells into C57/BL6 mice and tumor size increased rapidly with time in a cell number dependent manner.After the third immunization,mice were challenged subcutaneously with 5×l0 5 MS ＋ B16 cells.Compared with that of the negative control immunized with phosphate-buffered saline（PBS）,a significant reduction of tumor growth was observed in groups immunized with survivin plasmid DNA and MUC1 VNTRs plasmid DNA.Thus,the suppression of subcutaneous tumor was antigen-specific.This model is useful for the development of tumor vaccines targeting survivin and MUCI VNTRs.展开更多
Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based ...Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.展开更多
Two eukaryotic vectors expressing 9 tandem repeats of human MUCI（VNTR）, VR1012-VNTR, and pEGFP-VNTR, were constructed by cloning VNTR gene into VR1012 and pEGFP, respectively. VNTR stably expressing murine Lewis lun...Two eukaryotic vectors expressing 9 tandem repeats of human MUCI（VNTR）, VR1012-VNTR, and pEGFP-VNTR, were constructed by cloning VNTR gene into VR1012 and pEGFP, respectively. VNTR stably expressing murine Lewis lung carcinoma（LLC） cell line（VNTR^＋ LLC） was established by Lipofectamine-mediated transfection of pEGFP-VNTR into LLC cells. The EGFP expression was observed under a fluorescent microscope and VNTR expression in VNTR^＋ LLC cells was confirmed by means of Western blotting. A syngenic graft tumor model was generated by subcutaneous injection of VNTR^＋ LLC cells into C57/BL6 mice and tumor size increased rapidly with time and in a cell qumber dependent manner. VNTR mRNA expression in the tumor formed was confirmed by RT-PCR. After the third immunization mice were challenged subcutaneously with 5×10^5 VNTR^＋ LLC cells, a significant reduction of subcutaneous tumor growth was observed in the groups immunized with VNTR plasmid DNA compared with that in the groups immunized with the vector DNA alone. Thus, the suppression of subcutaneous tumor was antigen-specific. This model is useful for the development of tumor vaccines targeting MUCI VNTRs.展开更多
To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with t...To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups： the rats were treated by 0.9 % NS （n=24, control group）, inosine＋vitamin C （n=40, InV group）, Danshen （n=40, DS group） and 5-FU （n=40, 5-FU group）, respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU （P〈0.01）. No significant difference in protective effect was observed between DS group and lnV group （P〉0.05）. Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine＋vitamin C （P〈0.01）. No significant difference in this regard existed between DS group and 5-FU group （P〉0.05）. The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were lower than those in control group and InV group, with the differences being significant （P〈0.01）. No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF （P〉0.05） but ICAM-1 （P〈0.05）. It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.展开更多
AIM: To investigate the expression of tumor-antigens and major histocompatibility complex(MHC)-machinery components in glioblastoma multiforme cell lines flow cytometry staining methods were applied.METHODS: Ten GBM c...AIM: To investigate the expression of tumor-antigens and major histocompatibility complex(MHC)-machinery components in glioblastoma multiforme cell lines flow cytometry staining methods were applied.METHODS: Ten GBM cell lines(three commercially available: U-87 MG, U-138-MG and GMS-10 as well as seven newly established cell lines from individual patients in low-passages: HROG02, HROG04, HROG05, HROG06, HROG10, HROG13 and HROG17) were analyzed for expression of(Ⅰ) general and(Ⅱ) GBMrelated tumor antigens as well as of(Ⅲ) components of the MHC machinery by flow cytometry.RESULTS: All cell lines expressed MHC class?Ⅰ?with seven out of the ten being HLA-A02 positive. Four of the seven primary cell lines additionally expressedMHC class Ⅱ in a constitutive manner. Of note, after interferon gamma(IFN-γ) treatment, all seven cell lines expressed MHC class Ⅱ. The tumor associated antigens(TAA) EGFR and survivin were expressed at high levels in all cell lines; whereas MART-1, RHAMM, WT-1 and IL-13Rα were expressed by at least half of the cell lines and HER2/neu, MAGE-1 and tyrosinase were expressed only by few cell lines. However, all cell lines expressed at least two of the candidate antigens included into this analysis.CONCLUSION: No obvious differences between commercially available and newly-established cell lines were observed. Thus, the latter in low-passages are interesting for(therapy-) screening and immunotherapeutic strategies.展开更多
Simulation code for a model of the adaptive immune response seen in flavivirus infections is used to explain the immunopathological consequences seen in West Nile Virus virus (WNV) infections. We use a model that spec...Simulation code for a model of the adaptive immune response seen in flavivirus infections is used to explain the immunopathological consequences seen in West Nile Virus virus (WNV) infections. We use a model that specifically handles the differences in how the virus infects resting cells, the G0 state, versus dividing cells, the G1 state, which includes vastly increased MHC-I upregulation for resting cells over dividing cells. The simulation suggests how the infection progresses in a one host model and the results shed insight into the unusual survival curve data obtained for this infection: there is an increase in health even though viral load has increased.展开更多
目的筛选乙肝病毒(hepatitis B virus,HBV)DNA阴性的乙肝表面抗原(hepatitis B surface antigen,HBsAg)和乙肝表面抗体(hepatitis B surface antibody,HBsAb)阳性的慢性乙型肝炎(chronic hepatitis B,CHB)患者的血清危险因素,探讨危险...目的筛选乙肝病毒(hepatitis B virus,HBV)DNA阴性的乙肝表面抗原(hepatitis B surface antigen,HBsAg)和乙肝表面抗体(hepatitis B surface antibody,HBsAb)阳性的慢性乙型肝炎(chronic hepatitis B,CHB)患者的血清危险因素,探讨危险因素评分与预后的相关性。方法筛选2020年1月~2022年6月江苏大学附属金坛第一人民医院收治的HBV-DNA阴性的CHB患者193例,其中HBsAg和HBsAb阳性的119例患者作为观察组,HBsAg阳性且HBsAb阴性的74例患者作为对照组。收集所有患者的临床资料并计算外周血炎性指标[嗜中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR),血小板-淋巴细胞比值(platelet-to-lymphoccyte ratio,PLR),全身免疫炎症指数(systemic immune inflammatory index,SII)]和肝纤维化指标[谷氨酰转肽酶-血小板比值(gamma-glutamyl transpeptidase to platelet ratio,GPR),门冬氨酸转移酶纤维化指数(aspartate aminotransferase to platelet ratio index,APRI),肝纤维化4因子指数(fibrosis 4 score,FIB-4)],采用t检验和U检验比较两组间各指标的差异。采用ROC曲线评价差异指标的预测价值,多因素回归分析影响HBsAg和HBsAb阳性模式的危险因素。随访观察组患者二年内HBsAg和HBsAb变化,将20例HBsAg水平明显降低的患者作为预后良好组,24例HBsAg水平没有明显降低甚至HBsAb消失的患者作为预后不良组。结果与对照组相比,观察组的PLT水平[(181.07±63.31)×10^(9)/L vs(158.27±61.55)×10^(9)/L]和TP水平[70.20(65.73,74.90)g/L vs 67.00(64.45,71.25)g/L]明显升高,差异有统计学意义(t=2.459,U=3254.00,均P<0.05);而观察组的HBsAg水平[1.60(0.37,13.15)IU/ml vs 138.78(8.66,161.94)IU/ml]和APRI比值[0.31(0.22,0.47)vs 0.46(0.32,0.71)]明显降低,差异有统计学意义(U=1685.50,2972.00,均P<0.05)。ROC曲线确定PLT,TP,APRI和HBsAg在两组间的差异的截断值分别为157.50×10^(9)/L,69.45 g/L,0.29和22.56 IU/ml。单因素回归分析结果显示,PLT≥157.50×10^(9)/L,TP≥69.45 g/L,APRI≤0.29,HBsAg≤22.56IU/ml与CHB患者的HBsAg和HBsAb阳性模式相关(χ^(2)=8.231~50.862,均P<0.05);多因素回归分析显示,HBsAg≤22.56 IU/ml[OR(95%CI):9.853(4.722~20.560)]和TP≥69.45 g/L[OR(95%CI):2.358(1.132~4.912)]是HBsAg和HBsAb阳性模式的独立危险因素(均P<0.05)。基于上述危险因素建立的评分模型预测HBsAg和HBsAb阳性模式发生的ROC曲线下面积(area under curve,AUC)为0.703,灵敏度和特异度分别为66.7%和73.9%。随访结果显示,预后良好组主要分布在评分模型的高分段(2分),而预后不良组主要分布在评分模型的低分段(0分和1分),差异有统计学意义(χ^(2)=13.838,P=0.001)。结论HBsAg≤22.56 IU/ml和TP≥69.45 g/L是影响HBV-DNA阴性且HBsAg与HBsAb阳性的CHB患者的独立危险因素,据此建立的评分模型对上述患者的预后有一定的预测价值。展开更多
基金Supported by Specialized Research Fund for the Doctoral Program of Higher Education of China,No.20093420120005National Science Foundation of China,No.30771907
文摘AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.
基金Supported by the National Natural Science Foundation of China(No.30872396)the Scientific Research Foundation of Jilin Province,China(Nos.20080709,200905169)the Jilin University Basic Research Project,China(No.200903255)
文摘The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin and VNTR genes into VR1012,respectively.The eukaryotic vector pEGFP expressing survivin and MUC1 VNTRs fusion gene pEGFP-MS was also constructed.Mouse melanoma cell line（B16） stably expressing survivin and MUC1 VNTRs（MS ＋ B16） was established by Lipofectamine-mediated transfection of pEGFP-MS into B16 cells.EGFP expression in MS ＋ B16 cells was observed using a fluorescent microscope and survivin and MUC1 VNTRs（MS） expression was confirmed by means of Western blot analysis.A syngenic graft tumor model was generated by subcutaneous injection of MS ＋ B16 cells into C57/BL6 mice and tumor size increased rapidly with time in a cell number dependent manner.After the third immunization,mice were challenged subcutaneously with 5×l0 5 MS ＋ B16 cells.Compared with that of the negative control immunized with phosphate-buffered saline（PBS）,a significant reduction of tumor growth was observed in groups immunized with survivin plasmid DNA and MUC1 VNTRs plasmid DNA.Thus,the suppression of subcutaneous tumor was antigen-specific.This model is useful for the development of tumor vaccines targeting survivin and MUCI VNTRs.
基金Supported by The project Competitiveness Operational Programme(COP)A1.1.4.,No.P_37_798,Contract 149/26.10.2016(My SMIS2014+:106774)
文摘Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.
文摘Two eukaryotic vectors expressing 9 tandem repeats of human MUCI（VNTR）, VR1012-VNTR, and pEGFP-VNTR, were constructed by cloning VNTR gene into VR1012 and pEGFP, respectively. VNTR stably expressing murine Lewis lung carcinoma（LLC） cell line（VNTR^＋ LLC） was established by Lipofectamine-mediated transfection of pEGFP-VNTR into LLC cells. The EGFP expression was observed under a fluorescent microscope and VNTR expression in VNTR^＋ LLC cells was confirmed by means of Western blotting. A syngenic graft tumor model was generated by subcutaneous injection of VNTR^＋ LLC cells into C57/BL6 mice and tumor size increased rapidly with time and in a cell qumber dependent manner. VNTR mRNA expression in the tumor formed was confirmed by RT-PCR. After the third immunization mice were challenged subcutaneously with 5×10^5 VNTR^＋ LLC cells, a significant reduction of subcutaneous tumor growth was observed in the groups immunized with VNTR plasmid DNA compared with that in the groups immunized with the vector DNA alone. Thus, the suppression of subcutaneous tumor was antigen-specific. This model is useful for the development of tumor vaccines targeting MUCI VNTRs.
文摘To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups： the rats were treated by 0.9 % NS （n=24, control group）, inosine＋vitamin C （n=40, InV group）, Danshen （n=40, DS group） and 5-FU （n=40, 5-FU group）, respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU （P〈0.01）. No significant difference in protective effect was observed between DS group and lnV group （P〉0.05）. Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine＋vitamin C （P〈0.01）. No significant difference in this regard existed between DS group and 5-FU group （P〉0.05）. The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were lower than those in control group and InV group, with the differences being significant （P〈0.01）. No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF （P〉0.05） but ICAM-1 （P〈0.05）. It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.
文摘AIM: To investigate the expression of tumor-antigens and major histocompatibility complex(MHC)-machinery components in glioblastoma multiforme cell lines flow cytometry staining methods were applied.METHODS: Ten GBM cell lines(three commercially available: U-87 MG, U-138-MG and GMS-10 as well as seven newly established cell lines from individual patients in low-passages: HROG02, HROG04, HROG05, HROG06, HROG10, HROG13 and HROG17) were analyzed for expression of(Ⅰ) general and(Ⅱ) GBMrelated tumor antigens as well as of(Ⅲ) components of the MHC machinery by flow cytometry.RESULTS: All cell lines expressed MHC class?Ⅰ?with seven out of the ten being HLA-A02 positive. Four of the seven primary cell lines additionally expressedMHC class Ⅱ in a constitutive manner. Of note, after interferon gamma(IFN-γ) treatment, all seven cell lines expressed MHC class Ⅱ. The tumor associated antigens(TAA) EGFR and survivin were expressed at high levels in all cell lines; whereas MART-1, RHAMM, WT-1 and IL-13Rα were expressed by at least half of the cell lines and HER2/neu, MAGE-1 and tyrosinase were expressed only by few cell lines. However, all cell lines expressed at least two of the candidate antigens included into this analysis.CONCLUSION: No obvious differences between commercially available and newly-established cell lines were observed. Thus, the latter in low-passages are interesting for(therapy-) screening and immunotherapeutic strategies.
文摘Simulation code for a model of the adaptive immune response seen in flavivirus infections is used to explain the immunopathological consequences seen in West Nile Virus virus (WNV) infections. We use a model that specifically handles the differences in how the virus infects resting cells, the G0 state, versus dividing cells, the G1 state, which includes vastly increased MHC-I upregulation for resting cells over dividing cells. The simulation suggests how the infection progresses in a one host model and the results shed insight into the unusual survival curve data obtained for this infection: there is an increase in health even though viral load has increased.
文摘目的筛选乙肝病毒(hepatitis B virus,HBV)DNA阴性的乙肝表面抗原(hepatitis B surface antigen,HBsAg)和乙肝表面抗体(hepatitis B surface antibody,HBsAb)阳性的慢性乙型肝炎(chronic hepatitis B,CHB)患者的血清危险因素,探讨危险因素评分与预后的相关性。方法筛选2020年1月~2022年6月江苏大学附属金坛第一人民医院收治的HBV-DNA阴性的CHB患者193例,其中HBsAg和HBsAb阳性的119例患者作为观察组,HBsAg阳性且HBsAb阴性的74例患者作为对照组。收集所有患者的临床资料并计算外周血炎性指标[嗜中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR),血小板-淋巴细胞比值(platelet-to-lymphoccyte ratio,PLR),全身免疫炎症指数(systemic immune inflammatory index,SII)]和肝纤维化指标[谷氨酰转肽酶-血小板比值(gamma-glutamyl transpeptidase to platelet ratio,GPR),门冬氨酸转移酶纤维化指数(aspartate aminotransferase to platelet ratio index,APRI),肝纤维化4因子指数(fibrosis 4 score,FIB-4)],采用t检验和U检验比较两组间各指标的差异。采用ROC曲线评价差异指标的预测价值,多因素回归分析影响HBsAg和HBsAb阳性模式的危险因素。随访观察组患者二年内HBsAg和HBsAb变化,将20例HBsAg水平明显降低的患者作为预后良好组,24例HBsAg水平没有明显降低甚至HBsAb消失的患者作为预后不良组。结果与对照组相比,观察组的PLT水平[(181.07±63.31)×10^(9)/L vs(158.27±61.55)×10^(9)/L]和TP水平[70.20(65.73,74.90)g/L vs 67.00(64.45,71.25)g/L]明显升高,差异有统计学意义(t=2.459,U=3254.00,均P<0.05);而观察组的HBsAg水平[1.60(0.37,13.15)IU/ml vs 138.78(8.66,161.94)IU/ml]和APRI比值[0.31(0.22,0.47)vs 0.46(0.32,0.71)]明显降低,差异有统计学意义(U=1685.50,2972.00,均P<0.05)。ROC曲线确定PLT,TP,APRI和HBsAg在两组间的差异的截断值分别为157.50×10^(9)/L,69.45 g/L,0.29和22.56 IU/ml。单因素回归分析结果显示,PLT≥157.50×10^(9)/L,TP≥69.45 g/L,APRI≤0.29,HBsAg≤22.56IU/ml与CHB患者的HBsAg和HBsAb阳性模式相关(χ^(2)=8.231~50.862,均P<0.05);多因素回归分析显示,HBsAg≤22.56 IU/ml[OR(95%CI):9.853(4.722~20.560)]和TP≥69.45 g/L[OR(95%CI):2.358(1.132~4.912)]是HBsAg和HBsAb阳性模式的独立危险因素(均P<0.05)。基于上述危险因素建立的评分模型预测HBsAg和HBsAb阳性模式发生的ROC曲线下面积(area under curve,AUC)为0.703,灵敏度和特异度分别为66.7%和73.9%。随访结果显示,预后良好组主要分布在评分模型的高分段(2分),而预后不良组主要分布在评分模型的低分段(0分和1分),差异有统计学意义(χ^(2)=13.838,P=0.001)。结论HBsAg≤22.56 IU/ml和TP≥69.45 g/L是影响HBV-DNA阴性且HBsAg与HBsAb阳性的CHB患者的独立危险因素,据此建立的评分模型对上述患者的预后有一定的预测价值。
