Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This...Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.展开更多
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiologic...Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.展开更多
AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, ...AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.展开更多
目的通过构建时间序列自回归移动平均模型(autoregressive integrated moving average model,ARIMA),对手足口发病趋势进行预测,探讨该模型在发病预测中的应用。方法从疾病监测信息报告管理系统提取北京市朝阳区2010年1月-2016年12月手...目的通过构建时间序列自回归移动平均模型(autoregressive integrated moving average model,ARIMA),对手足口发病趋势进行预测,探讨该模型在发病预测中的应用。方法从疾病监测信息报告管理系统提取北京市朝阳区2010年1月-2016年12月手足口病月发病数据。建立ARIMA季节乘积模型,对2010年1月-2015年12月的月发病数进行拟合,再以2016年1-12月的月发病数作为验证数据,评价其预测效果。结果通过对模型进行拟合优度及残差序列进行白噪声检验,最后选择了ARIMA(1,0,0)(1,1,0)_(12)为最佳模型。对2016年1-12月发病数进行预测,实际发病数均落入95%CI内,平均相对误差为49.37%。模型中加入2016年1-6月的月实际发病数,预测2016年7-12月的月发病数,平均相对误差为18.12%。结论 ARIMA季节模型可应用于手足口病等具有季节性变动特征的传染病预测。ARIMA模型短期预测手足口病的发病情况精度更高,可通过不断纳入新的实际观测值开展动态分析。ARIMA模型仅为一种数学工具,在实际防控及监测工作中,需要结合专业理论知识及具体情况进行分析。展开更多
目的了解北京市朝阳区不同户籍儿童监护人预防接种知识、态度、行为(Knowledge,Attitude and Practice,KAP)情况。方法采用系统抽样法,选取在北京市朝阳区连续居住半年以上,年龄范围在1~3岁的儿童及其监护人作为调查对象。采用问卷调查...目的了解北京市朝阳区不同户籍儿童监护人预防接种知识、态度、行为(Knowledge,Attitude and Practice,KAP)情况。方法采用系统抽样法,选取在北京市朝阳区连续居住半年以上,年龄范围在1~3岁的儿童及其监护人作为调查对象。采用问卷调查法,由经过培训的调查员入户调查儿童监护人预防接种KAP情况,采用多指标平均加权评分法评定KAP调查结果。结果本次调查共收集643份问卷。监护人KAP综合评分结果显示,知识评分>4分者占85.4%(549/643),态度评分>4分者占79.3%(510/643),行为评分>4分者占91.0%(585/643)。结论北京市朝阳区儿童监护人预防接种KAP情况良好,本地户籍与外省户籍监护人平均得分差异没有统计学意义,但仍有少数分值偏低的人群,应对此类人群采取针对性措施,改善其知信行情况,提高儿童预防接种率。展开更多
To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with CHC.Methods Total of 297 consecutive Chinese patients were enrolled,including 250 nave c...To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with CHC.Methods Total of 297 consecutive Chinese patients were enrolled,including 250 nave cases and 47 cases who were previously treated.Treatment duration was determined according to viral genotypes,prior treatment history and viral responses at week 4,12 and 24.Results Totally,235 patients(79.1%)completed treatment and 186(87.3%)achieved SVR.And 219 out of 289(75.8%)patients achieved HCV RNA negative at week 4(RVR)and 259 of 276(93.8%)at week 12.Among the 164 patients with RVR who completed follow-up,158(96.3%)achieved SVR.Patients with RVR had lower baseline viral loads than patients without RVR(P=0.034).The positive predictive value(PPV)of RVR for SVR was 90.7%(OR 2.10 vs.non-RVR,95%CI:0.50-8.7).Similar outcomes were observed among patients with HCV undetectable at week 12.Conclusions Viral suppression by week 4 is associated with a high rate of treatment success in treatment nave and experienced patients receiving individualized CHC therapy.展开更多
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： Hepatitis B surfhce antigen （HBsAg） Ioss/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 as...Background： Hepatitis B surfhce antigen （HBsAg） Ioss/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 ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-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-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： 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 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/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. Conclusions： 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.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
To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with ...To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.展开更多
基金supported by Beijing Science and Technology Commission(grant number Z211100002921059)National Science and Technology Major Projects of China(2017ZX10201201-001-006,2017ZX10201201-002-006,and 2018ZX10715-005-003-005)+5 种基金Digestive Medical Coordinated Development Center of Beijing Hospital Authority(XXZ0302 and XXT28)National Key R&D Program China(2022YFC2603505)Beijing Hospital Authority Clinical Medicine Development with Special Funding Support(XMLX 202127)High-Level Public Health Technical Personnel Training Program of Beijing the Municipal Health Commission(2022-3-050)Capital Health Research and Development of Special(2022-1-2172)HBV infection,Clinical Cure and Immunology Joint Laboratory for Clinical Medicine Capital Medical University.
文摘Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
基金National Natural Science Foundation of China(grant number 82272563 to B.S.)National Science and Technology Major Project of the Ministry of Science and Technology of China(grant number 2023ZD0501202 to B.S.)+4 种基金institutional grants allocated to the National Institute of Biological Sciences,Beijing(NIBS)from the Chinese Ministry of Science and Technology,Beijing Municipal Commission of Science and Technology,and Tsinghua Universitythe support from China Pharmaceutical University(grant number 3150140001 to S.F.)National Natural Science Foundation of China(grant numbers 82203653 to S.F.,82371957 to L.W.,and 82371956 to X.C.)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(grant number JYY2023-8 to X.C.)Research Grants Council of University Grants Committee Hong Kong(grant numbers 14113723,14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N,and AoE/M-402/20)。
文摘Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.
文摘AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.
文摘目的了解北京市朝阳区不同户籍儿童监护人预防接种知识、态度、行为(Knowledge,Attitude and Practice,KAP)情况。方法采用系统抽样法,选取在北京市朝阳区连续居住半年以上,年龄范围在1~3岁的儿童及其监护人作为调查对象。采用问卷调查法,由经过培训的调查员入户调查儿童监护人预防接种KAP情况,采用多指标平均加权评分法评定KAP调查结果。结果本次调查共收集643份问卷。监护人KAP综合评分结果显示,知识评分>4分者占85.4%(549/643),态度评分>4分者占79.3%(510/643),行为评分>4分者占91.0%(585/643)。结论北京市朝阳区儿童监护人预防接种KAP情况良好,本地户籍与外省户籍监护人平均得分差异没有统计学意义,但仍有少数分值偏低的人群,应对此类人群采取针对性措施,改善其知信行情况,提高儿童预防接种率。
文摘To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with CHC.Methods Total of 297 consecutive Chinese patients were enrolled,including 250 nave cases and 47 cases who were previously treated.Treatment duration was determined according to viral genotypes,prior treatment history and viral responses at week 4,12 and 24.Results Totally,235 patients(79.1%)completed treatment and 186(87.3%)achieved SVR.And 219 out of 289(75.8%)patients achieved HCV RNA negative at week 4(RVR)and 259 of 276(93.8%)at week 12.Among the 164 patients with RVR who completed follow-up,158(96.3%)achieved SVR.Patients with RVR had lower baseline viral loads than patients without RVR(P=0.034).The positive predictive value(PPV)of RVR for SVR was 90.7%(OR 2.10 vs.non-RVR,95%CI:0.50-8.7).Similar outcomes were observed among patients with HCV undetectable at week 12.Conclusions Viral suppression by week 4 is associated with a high rate of treatment success in treatment nave and experienced patients receiving individualized CHC therapy.
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.
文摘Background： Hepatitis B surfhce antigen （HBsAg） Ioss/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 ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-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-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： 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 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/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. Conclusions： 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.
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.
基金the National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26,Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX 202127)+1 种基金the capital health research and development of special public health project(2022-1-2172)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302).
文摘To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.
