HBV infection

  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)仍然是一个公共卫生问题。筛选HBV表面抗原(HBsAg)以及天冬氨酸转氨酶(AST)/丙氨酸转氨酶(ALT)的献血者可能在提供安全的血液制品方面发挥关键作用。我们调查了罗安达拒绝献血者中与HBV感染相关的特征,安哥拉。
    这是一项横断面研究,对164个拒绝的供体进行了研究。从2022年3月至5月,捐赠者进行了HBsAg筛查。总的来说,63.4%的HBV检测呈阳性。
    HBV阳性(29.2±8.02)的平均年龄低于HBV阴性(33.9±10.0)(p<0.001)。20至40年的捐赠者(赔率比[OR]:2.34,p=0.045),女性(OR:1.40,p=0.516),城市化地区居民(OR:1.23,p=0.530),低教育程度(OR:1.54,p=0.458),失业(OR:1.65,p=0.271),未婚(OR:1.41,p=0.616)可能会感染HBV。AST/ALT比值在HBV感染(2.07±1.42)高于HBV未感染(1.90±1.14)。约20%的HBV阳性被归类为急性肝病,而80%患有慢性肝病,基于AST/ALT比率。年龄从20到40岁(OR:1.97,p=0.305),女性(OR:1.61,p=0.557),来自非城市化的捐赠者(OR:1.69,p=0.557),教育程度低(OR:1.64,p=0.571),和失业供者(OR:1.81,p=0.289)可能发展为慢性肝病.
    我们的研究结果表明病毒性肝炎控制措施失败。当局应考虑包括HBV核酸检测,以确保在安哥拉早期识别HBV。
    UNASSIGNED: Hepatitis B virus (HBV) remains a public health concern. Blood donors screened for HBV surface antigen (HBsAg) along with aspartate transaminase (AST)/alanine aminotransferase (ALT) could play a key in providing safe blood products. We investigated the features related to HBV infection among rejected blood donors in Luanda, Angola.
    UNASSIGNED: This was a cross-sectional study conducted with 164 rejected donors. Donors were screened for HBsAg from March to May 2022. Overall, 63.4% tested positive for HBV.
    UNASSIGNED: The mean age of the HBV-positive (29.2 ± 8.02) was lower than the HBV-negative (33.9 ± 10.0) (p < 0.001). Donors between 20 and 40 years (odds ratio [OR]: 2.34, p = 0.045), females (OR: 1.40, p = 0.516), residents in urbanized areas (OR: 1.23, p = 0.530), low educational (OR: 1.54, p = 0.458), unemployed (OR: 1.65, p = 0.271), and unmarried (OR:1.41, p = 0.616) might be likely to contract HBV. AST/ALT ratio was higher in HBV-infected (2.07 ± 1.42) than in HBV-uninfected (1.90 ± 1.14). About 20% of HBV-positive were classified as having acute liver disease, while 80% with chronic liver disease, based on AST/ALT ratio. Age ranged from 20 to 40 years (OR: 1.97, p = 0.305), females (OR: 1.61, p = 0.557), donors from non-urbanized (OR: 1.69, p = 0.557), a low educational (OR: 1.64, p = 0.571), and unemployed donors (OR: 1.81, p = 0.289) were likely to develop chronic liver disease.
    UNASSIGNED: Our findings indicated the failure of viral hepatitis control measures. Authorities should consider including HBV nucleic acid testing to ensure early identification of HBV in Angola.
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  • 文章类型: Journal Article
    儿童慢性乙型肝炎病毒(HBV)感染仍然是一个重大的公共卫生挑战。HBV的自然史和治疗结果可以变化很大,影响管理策略。这项回顾性研究是在罗马尼亚东北部进行的,涉及148名诊断为慢性病毒性乙型肝炎的儿科患者。59名儿童接受了抗病毒治疗,而89名儿童没有接受治疗。主要目标之一是HBeAg(乙型肝炎e抗原)血清转换率,疾病进展和治疗反应的标志。在治疗组中,26名儿童(44%)在治疗后实现了HBeAg血清转换。相比之下,44未经治疗的儿童(49%)经历了自发性HBeAg血清转换,表明该人群子集内的自然分辨率很高。研究结果强调了未经治疗的儿科患者中自发性血清转换的显着比例,提示对慢性HBV感染儿童的治疗标准和时机进行潜在的重新评估。治疗组和未治疗组之间的血清转换率相当,强调需要基于病毒学,生物化学,和临床参数。需要进一步的研究来完善管理策略,以优化儿科HBV感染的长期结果。
    Chronic Hepatitis B virus (HBV) infection in children remains a significant public health challenge. The natural history and treatment outcomes of HBV can vary widely, influencing management strategies. This retrospective study was conducted in Northeast Romania and involved a cohort of 148 pediatric patients diagnosed with chronic viral Hepatitis B. Of these, 59 children underwent antiviral treatment while 89 were not treated. One of the main objectives was the rate of HBeAg (Hepatitis B-e antigen) seroconversion, a marker of disease progression and response to therapy. Among the treated group, 26 children (44%) achieved HBeAg seroconversion following therapy. In contrast, 44 of the untreated children (49%) experienced spontaneous HBeAg seroconversion, indicating a substantial rate of natural resolution within this population subset. The findings highlight a significant proportion of spontaneous seroconversion in untreated pediatric patients, suggesting a potential re-evaluation of treatment criteria and timing for children with chronic HBV infection. The comparable rates of seroconversion between treated and untreated cohorts underscore the need for individualized treatment approaches based on a combination of virological, biochemical, and clinical parameters. Further studies are required to refine management strategies to optimize long-term outcomes in pediatric HBV infections.
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  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)感染,作为一个严重的全球公共卫生问题,与免疫功能紊乱密切相关。在这里,制备了三十七个1-(吲哚啉-1-基)-2-(噻唑-4-基)乙-1-酮衍生物作为潜在的免疫调节抗HBV药物。抗HBV活性评价证实化合物11a可以显著抑制在野生和抗性HBV染色HBVDNA复制,IC50值为0.13μM和0.36μM,分别。初步作用机制研究表明,11a对细胞HBsAg分泌有抑制作用,能有效激活TLR7,从而诱导人PBMC细胞分泌TLR7调节的细胞因子IL-12、TNF-α和IFN-α。SPR分析证实11a可以以7.06μM的亲和力与TLR7蛋白结合。MD模拟预测11a可以与TLR7的结合袋中的残基形成紧密的相互作用。理化参数表现和药代动力学分析表明,11a表现出相对有利的药物样特性。考虑到所有的结果,化合物11a可能是开发新型免疫调节抗HBV药物的有希望的线索。
    Hepatitis B virus (HBV) infection, as a serious global public health issue, is closely related to the immune dysfunction. Herein, thirty-seven 1-(indolin-1-yl)-2-(thiazol-4-yl)ethan-1-one derivatives were prepared as potential immunomodulatory anti-HBV agents. Anti-HBV activity evaluation confirmed compound 11a could significantly suppress the HBV DNA replication in both wild and resistant HBV stains, with IC50 values of 0.13 μM and 0.36 μM, respectively. Preliminary action mechanism studies showed that 11a had an inhibitory effect on cellular HBsAg secretion and could effectively activate TLR7, thereby inducing the secretion of TLR7-regulated cytokines IL-12, TNF-α and IFN-α in human PBMC cells. SPR analysis confirmed that 11a could bind to TLR7 protein with an affinity of 7.06 μM. MD simulation predicted that 11a could form tight interactions with residues in the binding pocket of TLR7. Physicochemical parameters perdition and pharmacokinetic analysis indicated that 11a displayed relatively favorable drug-like properties. Considering all the results, compound 11a might be a promising lead for developing novel immunomodulatory anti-HBV agents.
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  • 文章类型: Journal Article
    背景:尽管HBV患者在免疫抑制治疗(IST)后有重新激活的风险,在日本,他们的风险管理状况尚不清楚。本研究旨在描述谁在ISTS期间接受HBV再激活的预防性管理的患者的比例与HBsAg的慢性HBV感染或解决HBV感染的患者。
    方法:从2011年4月至2021年6月,使用JMDC日本索赔数据库进行了一项回顾性队列研究。从数据库中确定接受IST的HBV感染HbsAg的患者或接受IST的已解决HBV感染的患者,并评估适当的管理以防止HBV再激活。
    结果:总计,确定了6242名合格患者。具有适当HBV再激活管理的患者比例,根据IST的HBV再激活风险水平进行分层,高风险为43.1%(276/641),中危患者为40.2%(223/555),低危患者为14.9%(741/4965)。当结果计算的评估期从360天缩短到180天时,高风险比例上升至52.7%。在高风险中,大型医院接受适当管理的优势比为2.16(95%CI1.12-4.44),中危患者为4.63(95%CI2.34-10.25),低危患者为3.60(95%CI3.07-4.24)。
    结论:HBV再激活管理是根据与IST相关的再激活风险定制的。然而,对HBV再激活管理指南的依从性次优,即使是高危患者。对于确保规模较小的医疗机构来说尤其如此,强调需要进一步的教育活动。
    该研究评估了在日本免疫抑制治疗期间以指南为基础的乙型肝炎病毒再激活管理的实施。乙型肝炎病毒治疗的适当管理涉及预防性核苷(t)ide类似物(NUC)治疗和定期监测乙型肝炎病毒DNA。本研究旨在使用日本医疗索赔数据库进行回顾性队列研究,评估这些管理实践在日本临床环境中实施的程度。该分析确定了6242名符合条件的患者,并确定他们是否接受了适当的管理,以防止乙肝病毒再激活的基础上与他们的免疫抑制治疗相关的风险水平。根据准则,高风险患者接受适当的再激活管理的比例为43.1%,中危患者为40.2%,低危免疫抑制治疗患者为14.9%。将评估期从360天缩短至180天显示,高危患者比例增加至52.7%,这表明免疫抑制治疗后持续监测的潜在挑战。研究表明,大型医院接受适当管理的患者几率更高。总的来说,坚持乙肝病毒再激活管理指南是次优的,尤其是在较小的医疗机构,强调需要更多的教育活动。
    BACKGROUND: Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection.
    METHODS: A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation.
    RESULTS: In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients.
    CONCLUSIONS: HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.
    The study assesses the implementation of guideline-based management of hepatitis B virus reactivation during immunosuppressive therapy in Japan. The appropriate management of hepatitis B virus treatment involves prophylactic nucleos(t)ide analog (NUC) therapy and regular monitoring of hepatitis B virus DNA. This study aims to assess the extent to which these management practices are implemented in a clinical setting in Japan using a retrospective cohort study using the Japanese Medical Claims Database. The analysis identified 6242 eligible patients and identified whether they received appropriate management to prevent hepatitis B virus reactivation based on the level of risk associated with their immunosuppressive therapy. Based on the guidelines, the proportions of patients receiving appropriate reactivation management were 43.1% for high-risk, 40.2% for intermediate-risk and 14.9% for low-risk immunosuppressive therapy patients. Shortening the evaluation period from 360 to 180 days showed an increase in the proportion of high-risk patients to 52.7%, which indicated the potential challenge for continued monitoring after immunosuppressive therapy administration. The study shows that large hospitals present higher odds of patients receiving appropriate management. Overall, adherence to hepatitis B virus reactivation management guidelines was suboptimal, especially in smaller medical institutions, emphasizing the need for additional educational activities.
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  • 文章类型: Journal Article
    在印度,据估计,有40万人患有乙型肝炎病毒(HBV)。病毒负担的量化是管理中的重要实验室工具。然而,不同HBV-DNA检测方法的广泛使用仍然受到高成本和可变诊断精度的影响。本研究是通过Truenat®-PCR评估ALT水平与HBV-DNA的诊断精度和相关性。
    在这项前瞻性横断面研究中,通过快速HBsAg从患者中收集了总共567份血清,并进行肝功能检查(LFT)。通过Truenat®-PCR测试进行病毒HBV-DNA扩增检测。
    在567个样本中,通过快速和Truenat®-PCR发现452个样品为阳性,106个HBV-DNA阴性,随后9个无效。在73%的阳性患者中发现高ALT水平HBV-DNA水平(>100000拷贝/ml),与那些低于100000拷贝/ml的患者相比,447例患者明显更高。
    Truenat®-PCR技术是一种高度敏感的,可以用低资源进行有效控制HBV感染。对HBV-DNA水平和血清ALT水平的评估显示,患者存在持续的病毒复制和疾病进展的显着比例。
    UNASSIGNED: In India, it is estimated that there are 40 million people suffering from Hepatitis B virus (HBV). Quantification of the viral burden is an important laboratory tool in the management. However, widespread use of different HBV-DNA assays is still affected by the high cost and variable diagnostic precision. The present study was conducted to evaluate the diagnostic precision and co-relation of ALT levels with HBV-DNA by Truenat®-PCR.
    UNASSIGNED: In this prospective cross-sectional study a total of 567 serums were collected from patients by rapid HBsAg, and processed for liver function tests (LFT). The viral HBV-DNA amplification detection was carried out through by Truenat®-PCR test.
    UNASSIGNED: Out of 567 samples, 452 samples were found to be positive by both rapid and Truenat®-PCR and 106 were negative for HBV-DNA followed by 9 invalid. High ALT level found in 73% of positive patients who had HBV-DNA level (>100000 copies/ml) which is significantly higher in 447 patients as compared to those have below ≤100000 copies/ml.
    UNASSIGNED: Truenat®-PCR technique is a highly sensitive and can be performed with low resources for effective control of HBV infection. Evaluation of HBV-DNA levels and serum ALT levels showed a significant proportion of patient harbored ongoing viral replication and disease progression.
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  • 文章类型: Meta-Analysis
    背景:目前的指南缺乏关于HBcAb+供体肾移植后是否应给予抗病毒prophylaxes的共识。本系统评价和荟萃分析旨在评估新发HBV(DNH)感染的发生率和危险因素,以及移植和病人的生存。
    方法:我们搜索了PubMed,Embase,以及截至2023年12月31日的Cochrane图书馆。我们纳入了使用HBcAb+肾脏移植后评估临床结果的相关研究。患病率的效果汇总指标和95%置信区间(CI),危险因素,使用随机效应荟萃分析评估移植物和患者的存活率.
    结果:最终分析包括13项研究。DNH发生率为0.36%(9/2516),异质性低(I2=6%)。HBsAb+接受者(OR:0.78,95CI:0.25-2.38),HBcAb+接受者(OR:3.11,95CI:0.91-10.66,P=0.071),和未接受任何抗病毒预防的受者(OR:1.26,95CI:0.15-10.58)与较高的DNH风险无关.具体来说,HBsAb-/HBcAb+接受者的DNH发生率最高(4.65%),其次是HBsAb-/HBcAb-(0.49%),HBsAb+/HBcAb-接受者(0.45%),和HBsAb+/HBcAb+(0%)。此外,与接受HBcAb+肾脏的受者相比,接受HBcAb+肾脏的受者具有相当的移植物存活率(HR:1.06,95CI:0.94-1.19,P=0.55)和患者存活率(HR:1.16,95CI:0.98-1.38,P=0.090).
    结论:利用HBcAb+肾脏的肾移植有助于相当的移植物和患者生存,HBV传播的风险极低。抗病毒药物只能在HBsAb-/HBcAb+接受者中施用。
    BACKGROUND: Current guidelines lack consensus on whether antiviral prophylaxes should be administered after kidney transplantation from HBcAb+ donors. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of de novo HBV (DNH) infection, as well as graft and patient survival.
    METHODS: We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023. We included relevant studies that assessed clinical outcomes following transplantation utilizing HBcAb+ kidneys. Summary measures of effect and 95% confidence intervals (CI) for prevalence, risk factors, as well as graft and patient survival were estimated using random-effects meta-analysis.
    RESULTS: Thirteen studies were included for the final analysis. The DNH incidence was at 0.36% (9/2516) with low heterogeneity (I2 = 6%). HBsAb+ recipients (OR: 0.78, 95%CI: 0.25-2.38), HBcAb+ recipients (OR: 3.11, 95%CI: 0.91-10.66, P = 0.071), and recipients not receiving any antiviral prophylaxis (OR: 1.26, 95%CI: 0.15-10.58) were not associated with higher DNH risk. Specifically, HBsAb-/HBcAb+ recipients had the highest DNH incidence (4.65%), followed by HBsAb-/HBcAb- (0.49%), HBsAb+/HBcAb- recipients (0.45%), and HBsAb+/HBcAb+ (0%). Furthermore, recipients receiving HBcAb+ kidneys had comparable graft survival (HR: 1.06, 95%CI: 0.94-1.19, P = 0.55) and patient survival (HR:1.16, 95%CI: 0.98-1.38, P = 0.090) compared with recipients receiving HBcAb- kidneys.
    CONCLUSIONS: Kidney transplantation utilizing HBcAb+ kidneys contributed to comparable graft and patient survival with an extremely low risk of HBV transmission. Antiviral prophylaxes may only be administered in HBsAb-/HBcAb+ recipients.
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  • 文章类型: Journal Article
    弥漫性大B细胞淋巴瘤(DLBCL)的发展与宿主感染状态密切相关。中国是乙型肝炎病毒(HBV)感染的高度流行地区。目前尚不清楚HBV感染是否对不同治疗设置的DLBCL患者的预后影响具有一致的影响。
    我们在2011年7月至2022年7月期间对吉林大学第一医院的692例接受CHOP或R-CHOP方案治疗的DLBCL患者进行了一项队列研究。根据乙型肝炎表面抗原(HBsAg)状态将患者分为两组:HBsAg阳性(n=84,12.1%)和HBsAg阴性(n=608,87.9%)组。收集来自180例原发性DLBCL患者的肿瘤样本用于下一代测序(NGS)。
    HBsAg阳性组有更频繁的肝功能异常(P=0.003),低蛋白血症(P<0.001),>2个结外器官的发生率(P=0.011),和脾脏受累(P<0.001)比HBsAg阴性组。HBsAg阳性患者具有较低的完全反应(CR)和总反应率(ORR)率(所有P值<0.05),在CHOP组或R-CHOP组中。在接受R-CHOP的患者中,12个月和24个月内疾病进展率在HBsAg阳性组高于HBsAg阴性组(P=0.018,P=0.029).然而,CHOP组HBsAg阳性和HBsAg阴性患者的疾病进展无显著差异(P>0.05)。HBsAg阳性(OS:HR[95%CI]=2.511[1.214-5.192],P=0.013)仅与CHOP组的OS较差相关。而在R-CHOP组中,HBsAg阳性与较差的OS和PFS(OS:HR[95%CI]=1.672[1.050-2.665],P=0.030;PFS:HR[95%CI]=1.536[1.013-2.331],P=0.043)。此外,HBsAg阳性DLBCL患者在MYC中的突变发生率也较高,ATM,PTPN6和表观遗传调控基因。
    这些研究结果表明,HBsAg阳性DLBCL患者可能是一个不同的亚组,预后较差。标准疗法可能不足,应在更好地了解化学耐药的潜在机制的基础上开发新的治疗策略。
    The development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings.
    We conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS).
    The HBsAg-positive group had more frequent abnormal liver function (P = 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P = 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes.
    These findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance.
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  • 文章类型: Journal Article
    免疫细胞在慢性乙型肝炎病毒(HBV)感染的发展中起着至关重要的作用,导致肝硬化和肝细胞癌(HCC)。然而,它们在不同疾病阶段的功能尚未完全了解。
    在这项研究中,我们使用单细胞RNA测序(scRNA-seq)来表征不同疾病阶段的人类肝脏免疫微环境。我们分析了从六个健康个体的肝脏获得的118,455个免疫细胞的scRNA-seq数据,4例HBV感染,5例HBV肝硬化患者,和3例HBV相关HCC患者。
    我们的结果显示,在疾病进展过程中,瘢痕相关巨噬细胞的积累,我们确定了两个相关的免疫亚群,巨噬细胞-CD9/IL18和巨噬细胞-CD9/IFI6。巨噬细胞-CD9/IL18从HBV感染扩展到肝硬化,而巨噬细胞-CD9/IFI6从肝硬化扩展到HCC。我们使用多重免疫荧光染色验证了巨噬细胞CD9/IFI6的存在。我们还发现在从肝硬化到HCC的进展过程中细胞毒性NK细胞-GNLY的增加。此外,CD4T细胞-TNFAIP3,CD8T细胞-TNF(效应CD8T细胞)的比例,和CD8T细胞-CD53增加,而从HBV感染到肝硬化,Treg细胞的比例下降。Treg和CD8T细胞-LAG3(耗尽的CD8T细胞)的比例增强,而CD8T细胞-TNF(效应CD8T细胞)的比例从肝硬化到HCC降低。此外,GSEA富集分析显示MAPK,ERBB,从HBV感染到肝硬化和HCC,髓系细胞中的P53信号通路逐渐受到抑制。
    我们的研究为HBV相关肝病进展期间肝脏免疫环境的变化提供了重要的见解,这可能有助于改善HBV感染的肝脏疾病的管理。
    Immune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood.
    In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the human liver immune microenvironment at different disease stages. We analyzed scRNA-seq data from 118,455 immune cells obtained from livers of six healthy individuals, four patients with HBV infection, five patients with HBV cirrhosis, and three patients with HBV-associated HCC.
    Our results showed an accumulation of scar-associated macrophages during disease progression, and we identified two relevant immune subsets, Macrophage-CD9/IL18 and macrophage-CD9/IFI6. Macrophage-CD9/IL18 expanded from HBV infection to cirrhosis, while macrophage-CD9/IFI6 expanded from cirrhosis to HCC. We verified the existence of Macrophage-CD9/IFI6 using multiplex immunofluorescence staining. We also found an increase in cytotoxic NK Cell-GNLY during progression from cirrhosis to HCC. Additionally, the proportion of CD4 T cell-TNFAIP3, CD8 T cell-TNF (effector CD8 T cells), and CD8 T cell-CD53 increased, while the proportion of Treg cells decreased from HBV infection to cirrhosis. The proportion of Treg and CD8 T cell-LAG3 (Exhausted CD8 T cell) enhanced, while the proportion of CD8 T cell-TNF (effector CD8 T cells) decreased from cirrhosis to HCC. Furthermore, GSEA enrichment analyses revealed that MAPK, ERBB, and P53 signaling pathways in myeloid cells were gradually inhibited from HBV infection to cirrhosis and HCC.
    Our study provides important insights into changes in the hepatic immune environment during the progression of HBV-related liver disease, which may help improve the management of HBV-infected liver diseases.
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  • 文章类型: Journal Article
    目的:我们的目的是研究丁型肝炎病毒(HDV)的患病率和进展为严重肝脏相关事件(SLRE)的风险在HBsAg阳性的人与艾滋病毒(PLWH)在意大利;HDV-RNA拷贝水平的作用,还研究了HCV合并感染和最低点CD4计数。
    方法:招募来自意大利基金会队列的HIV感染者(PLWH)与可用HBsAg和HDVAb的初始抗逆转录病毒药物(ICONA)。HBsAg,HDVAb,检测HDV-RNA和HDV基因型。
    方法:从首次HDV筛查到严重肝脏相关事件的时间(SLRE:失代偿期肝硬化,肝移植,HCC)。使用精细灰色回归模型来评估HDVAb的关联,HDV-RNA,HDV/HCV合并感染,CD4最低点和结果。次要终点:SLRE或死亡时间;HDVAb和HDV-RNA患病率。
    结果:共有152/809(18.8%)HBsAg阳性PLWH显示HDVAb反应性;63/93(67.7%)为HDV-RNA阳性。作为男性,注射毒品(PWID)的人,HCVAb阳性,FIB-4>3.25是HDVAb阳性的独立因素。在5年的中位随访中,37PLWH(5年时4.1%)出现SLRE,97(12.0%)达到SLRE或死亡终点。HDV-RNA阳性(独立于HDV-RNA拷贝水平)PLWH的SLRE风险比HDV阴性高4.6倍(95CI2.0-10.5)。HCVAb和HDVAb的PLWH阳性显示SLRE的独立风险最高(ASHR:11.9,95CI:4.6-30.9vs.HCVneg/HDVneg)。最低CD4<200/mL与SLRE相关(ASHR:3.9,95%1.0-14.5)。
    结论:五分之一的HBsAg阳性PLWH港HDV感染,并且有进展为晚期肝病的高风险。HCV导致更坏的结果。这个群体迫切需要有效的治疗。
    OBJECTIVE: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated.
    METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested.
    METHODS: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence.
    RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5).
    CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.
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  • 文章类型: Journal Article
    目的:血液和肝纤维化标志物可用于有效监测慢性乙型肝炎病毒(HBV)感染,从而增加患者的治疗结果。这项研究的目的是评估全血细胞计数(CBC)和非侵入性肝纤维化指数作为HBV感染的预后结果和监测指标的适用性。
    结果:白细胞水平和差异计数的显著差异,红细胞计数,血红蛋白指数,观察HBV感染患者(病例)和未感染患者(对照)之间的血小板指数。血红蛋白(Hb)水平,总白细胞(tWBC),中性粒细胞,单核细胞,血小板,与对照组相比,这些病例的血小板分布宽度(PDW)显着降低(p<0.05)。总胆红素和间接胆红素;脱脂比,与对照组相比,天冬氨酸转氨酶与血小板比率指数(APRI)和RDW与血小板比率(RPR)升高(p值<0.05)。在多变量调整模型中,测试标记的显著性,血红蛋白指数(β系数=-0.876,p值<0.001),NLR(β系数=-0.839,p值<0.001),MPV_10000(β系数=-0.333,p值<0.001)和白蛋白(β系数=-0.059,p值=0.014),与HBV感染状态相关。受试者操作特征曲线分析显示,血红蛋白指数(AUC=0.744)和MPV_10000(AUC=0.730)是HBV感染的更好预后指标。
    OBJECTIVE: Haematological and liver fibrotic markers could be appreciably utilized for effective monitoring of Chronic Hepatitis B viral (HBV) infection, thereby increasing patient\'s treatment outcome. The objective of this study was to assess the applicability of complete blood count (CBC) and non-invasive liver-fibrotic indices as markers of prognostic outcome and monitoring in HBV infections.
    RESULTS: Significant differences in levels of white cell and differentials counts, red blood cell count, hemoglobin indices, and platelet indices were observed between HBV-infected patients (cases) and uninfected persons (controls). Levels of haemoglobin (Hb), total white blood cells (tWBC), neutrophils, monocytes, platelets, and Platelet Distribution width (PDW) were significantly lower (p < 0.05) in the cases compared to the controls. Total and indirect bilirubin; De-Ritis ratio, Aspartate transaminase to platelet ratio index (APRI) and RDW-to-platelet ratio (RPR) were elevated in cases compared with controls (p-value < 0.05). In a multivariate adjusted model to test the significance of markers, Hemoglobin Index (beta coefficient = - 0.876, p-value < 0.001), NLR (beta coefficient = - 0.839, p-value < 0.001), MPV_10000 (beta coefficient = - 0.333, p-value < 0.001) and Albumin (beta coefficient = - 0.059, p-value = 0.014), were associated with HBV infection status. Receiver operative characteristics curve analysis showed Hemoglobin Index (AUC = 0.744) and MPV_10000 (AUC = 0.730) as better prognostic markers for HBV-infection.
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