chronic liver disease

慢性肝病
  • 文章类型: Journal Article
    肠-肝轴包括肠和肝脏之间的双向通信,因此涵盖了从肝脏到肠道以及从肠道到肝脏的信号。肠-肝轴的破坏与慢性肝病的进展有关。包括酒精相关和代谢功能障碍相关的脂肪变性肝病和胆管疾病。免疫细胞及其模式识别受体的表达,激活标记或免疫检查点可能在肠道和肝脏之间的交流中起着积极的作用。这里,我们提出了一个26色全光谱流式细胞术小组,用于人类细胞破译循环免疫细胞在慢性肝病进展过程中肠-肝通讯中的作用,已被优化用于患者来源的全血样本,最丰富的临床材料。我们的小组专注于模式识别受体的变化,包括toll样受体(TLR)或Dectin-1,还包括其他免疫调节分子,如胆汁酸受体和检查点分子。此外,该小组可用于跟踪慢性肝病的进展,并可用作评估针对微生物介质或调节免疫细胞活化的治疗靶标的效率的工具。
    The gut-liver axis includes the bidirectional communication between the gut and the liver, and thus covers signals from liver-to-gut and from gut-to-liver. Disruptions of the gut-liver axis have been associated with the progression of chronic liver diseases, including alcohol-related and metabolic dysfunction-associated steatotic liver disease and cholangiopathies. Immune cells and their expression of pattern recognition receptors, activation markers or immune checkpoints might play an active role in the communication between gut and liver. Here, we present a 26-color full spectrum flow cytometry panel for human cells to decipher the role of circulating immune cells in gut-liver communication during the progression of chronic liver diseases in a non-invasive manner, which has been optimized to be used on patient-derived whole blood samples, the most abundantly available clinical material. Our panel focuses on changes in pattern recognition receptors, including toll-like receptors (TLRs) or Dectin-1, and also includes other immunomodulatory molecules such as bile acid receptors and checkpoint molecules. Moreover, this panel can be utilized to follow the progression of chronic liver diseases and could be used as a tool to evaluate the efficiency of therapeutic targets directed against microbial mediators or modulating immune cell activation.
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  • 文章类型: Journal Article
    一名患有慢性肝病和难治性腹水的65岁男性正在接受肝移植评估,怀疑缩窄性心包炎(CP)。由于利尿过多,初始诊断尚无定论。利尿剂停药后,心脏磁共振证实CP,导致成功的心包切除术和肝功能正常化,强调容量状态和多模态成像在CP诊断中的作用。
    A 65-year-old male with chronic liver disease and refractory ascites was being evaluated for liver transplant, when constrictive pericarditis (CP) was suspected. Initial diagnostics were inconclusive due to overdiuresis. After suspension of diuretics, cardiac magnetic resonance confirmed CP, leading to successful pericardiectomy and normalization of liver function, emphasizing volume status and multimodality imaging role in CP diagnosis.
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  • 文章类型: Journal Article
    使用基于对比增强CT的影像组学特征和临床特征开发了组合模型,以预测慢性肝病(CLD)患者的肝纤维化分期。我们回顾性分析了多期CT扫描和活检证实的肝纤维化。160例CLD患者随机分为7:3训练/验证比例。使用Spearman相关性和多变量logistic回归相关性确定与肝纤维化相关的临床实验室指标。从多相CT图像分割整个肝脏后,提取放射学特征。使用RF-RFE进行特征降维,拉索,和mRMR方法。在112名患者的训练队列中开发了6个基于影像组学的模型。对48例随机分配的患者进行内部验证。构建受体工作特征(ROC)曲线和混淆矩阵以评估模型性能。影像组学模型表现出强大的性能,显著纤维化的AUC值为0.810至1.000,晚期纤维化,和肝硬化。整合的临床-影像组学模型在验证队列中具有优越的诊断效能,AUC值为0.836至0.997。此外,这些模型优于已建立的生物标志物,如天冬氨酸转氨酶与血小板比率指数(APRI)和纤维化4评分(FIB-4),以及γ谷氨酰转肽酶与血小板的比率(GPR),预测纤维化阶段。临床影像组学模型作为CLD患者肝纤维化评估和分期的非侵入性诊断工具,具有相当大的前景。可能导致更好的患者管理和结果。
    A combined model was developed using contrast-enhanced CT-based radiomics features and clinical characteristics to predict liver fibrosis stages in patients with chronic liver disease (CLD). We retrospectively analyzed multiphase CT scans and biopsy-confirmed liver fibrosis. 160 CLD patients were randomly divided into 7:3 training/validation ratio. Clinical laboratory indicators associated with liver fibrosis were identified using Spearman\'s correlation and multivariate logistic regression correlation. Radiomic features were extracted after segmenting the entire liver from multiphase CT images. Feature dimensionality reduction was performed using RF-RFE, LASSO, and mRMR methods. Six radiomics-based models were developed in the training cohort of 112 patients. Internal validation was conducted on 48 randomly assigned patients. Receptor Operating Characteristic (ROC) curves and confusion matrices were constructed to evaluate model performance. The radiomics model exhibited robust performance, with AUC values of 0.810 to 1.000 for significant fibrosis, advanced fibrosis, and cirrhosis. The integrated clinical-radiomics model had superior diagnostic efficacy in the validation cohort, with AUC values of 0.836 to 0.997. Moreover, these models outperformed established biomarkers such as the aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis 4 score (FIB-4), as well as the gamma glutamyl transpeptidase to platelet ratio (GPR), in predicting the fibrotic stages. The clinical-radiomics model holds considerable promise as a non-invasive diagnostic tool for the assessment and staging of liver fibrosis in the patients with CLD, potentially leading to better patient management and outcomes.
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  • 文章类型: Journal Article
    持续的COVID-19大流行严重影响了特殊人群,包括免疫受损的个体,艾滋病毒感染者(PLWHIV),儿科患者,和那些患有慢性肝病(CLD)。本范围审查旨在绘制这些弱势群体感染各种SARS-CoV-2变体时的临床结果。审查确定了趋势和模式,注意到早期的变体,比如Alpha和Delta,与更严重的结果相关,包括更高的住院率和死亡率。相比之下,Omicron变体,尽管它的传播性增加了,往往会引起较温和的临床表现。由于患者人群的异质性和病毒的演变性质,该综述强调了持续监测和量身定制的医疗保健干预措施的必要性。持续监测和适应性医疗策略对于减轻COVID-19对这些高危人群的影响至关重要。
    The ongoing COVID-19 pandemic has significantly impacted special populations, including immunocompromised individuals, people living with HIV (PLWHIV), pediatric patients, and those with chronic liver disease (CLD). This scoping review aims to map the clinical outcomes of these vulnerable groups when infected with various SARS-CoV-2 variants. The review identifies trends and patterns, noting that early variants, such as Alpha and Delta, are associated with more severe outcomes, including higher hospitalization and mortality rates. In contrast, the Omicron variant, despite its increased transmissibility, tends to cause milder clinical manifestations. The review highlights the necessity for ongoing surveillance and tailored healthcare interventions due to the heterogeneity of patient populations and the evolving nature of the virus. Continuous monitoring and adaptive healthcare strategies are essential to mitigate the impact of COVID-19 on these high-risk groups.
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  • 文章类型: Journal Article
    人类慢性肝病患者的肠道微生物组的改变是众所周知的病理生理机制。因此,它代表了诊断和治疗的目标。在患有慢性肝病的狗中也发现了肠道菌群失调,但是缺乏评估合生元给药有效性的临床试验。将32只患有慢性肝胆疾病的狗平均随机分为两组:一组用合生元复合物治疗4-6周(TG),一组未治疗的对照组(CG)。所有的狗都接受了临床评估,完整的回忆,血液检查,腹部超声,粪便胆汁酸,和T0-T1(4-6周后)的肠道微生物组评估。与对照狗相比,处理的狗显示ALT活性(p=0.007)和胃肠道体征的临床消退(p=0.026)的显著降低。与对照组相比,合生元处理导致肠杆菌科和落叶草科的增加较低,但不影响细菌种类的总体丰富度和数量。合生元给药未检测到粪便胆汁酸谱的显着变化。需要进一步的研究来更好地评估这些患者中合生元给药的有效性以及确定临床和生化改善所涉及的代谢途径。
    Alteration in the gut microbiome in human patients with chronic liver disease is a well-known pathophysiological mechanism. Therefore, it represents both a diagnostic and therapeutical target. Intestinal dysbiosis has also been identified in dogs with chronic liver disease, but clinical trials evaluating the effectiveness of synbiotic administration are lacking. Thirty-two dogs with chronic hepatobiliary disease were equally randomized into two groups: one treated with a synbiotic complex for 4-6 weeks (TG) and one untreated control group (CG). All dogs underwent clinical evaluation, complete anamnesis, bloodwork, abdominal ultrasound, fecal bile acids, and gut microbiome evaluation at T0-T1 (after 4-6 weeks). Treated dogs showed a significant reduction in ALT activity (p = 0.007) and clinical resolution of gastrointestinal signs (p = 0.026) compared to control dogs. The synbiotic treatment resulted in a lower increase in Enterobacteriaceae and Lachnospiraceae compared to the control group but did not affect the overall richness and number of bacterial species. No significant changes in fecal bile acids profile were detected with synbiotic administration. Further studies are needed to better evaluate the effectiveness of synbiotic administration in these patients and the metabolic pathways involved in determining the clinical and biochemical improvement.
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    文章类型: Journal Article
    识别肝纤维化在管理慢性肝病患者中至关重要。肝病的病因可归因于多种因素,包括慢性病毒性肝炎,脂肪性肝病,如酒精相关肝病或代谢功能障碍相关的脂肪性肝病,自身免疫性肝炎,和胆汁淤积性肝病。目前,具有组织病理学评估的侵入性肝活检是金标准;然而,非侵入性测试变得越来越普遍,特别是因为它们没有侵入性手术如活检的风险。本文回顾了纤维化的非侵入性测试,将它们分为基于血液和基于成像的测试。
    Identifying hepatic fibrosis is paramount in managing patients with chronic liver disease. The etiology of liver disease can be owing to many factors, including chronic viral hepatitis, steatotic liver diseases such as alcohol-associated liver disease or metabolic dysfunction-associated steatotic liver disease, autoimmune hepatitis, and cholestatic liver diseases. Currently, invasive liver biopsy with histopathologic evaluation is the gold standard; however, noninvasive tests are becoming more prevalent, especially because they do not carry the risks of invasive procedures such as biopsy. This article reviews noninvasive tests for fibrosis, separating them into blood-based and imaging-based tests.
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  • 文章类型: Journal Article
    背景:早期发现慢性肝病(CLD)患者的进行性肝损害对于更好的治疗反应至关重要。多项研究表明microRNA(miRNA)在CLD进程中的作用与调节细胞增殖有关,纤维化,和细胞凋亡以及致癌作用。目标:该研究旨在确定由于乙型肝炎病毒(HBV)和非酒精性脂肪性肝病(NAFLD)引起的CLD患者不同阶段纤维化中miRNA-221的表达,从而评估其作为CLD早期生物标志物的作用。方法:本横断面研究共招募100名参与者(75例CLD患者和25例健康对照),分为四组,其中25人作为健康对照,25在无纤维化的CLD中,25例CLD伴纤维化,25例为肝硬化CLD。从血浆中提取总RNA,然后进行cDNA合成,最后,使用qRT-PCR方法分析miRNA-221的表达作为单一生物标志物的诊断潜力.结果:血浆miRNA-221水平在CLD不同纤维化阶段显著上调(p<0.05),这种上调与纤维化进展呈正相关(p<0.05)。显著增加的miRNA-221的表达被发现在NAFLD患者相比HBV患者在CLD无纤维化患者组(P<0.05),而miRNA-221的表达在CLD与纤维化组的HBV患者中显著上调。miRNA-221在区分不同阶段的纤维化与健康对照方面显示出高诊断准确性(p<0.05)。结论:miRNA-221可作为潜在的血浆生物标志物用于CLD患者纤维化进展的早期预测。
    Background: Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in regulating cell proliferation, fibrosis, and apoptosis as well as in carcinogenesis. Objectives: The study was aimed at determining the expression of miRNA-221 among different stages of fibrosis in CLD patients due to hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD) and thus evaluate its role as an early biomarker in CLD. Methods: A total of 100 participants (75 CLD patients and 25 healthy control) were recruited in this cross-sectional study and divided into four groups, of which 25 as healthy control, 25 in CLD without fibrosis, 25 were CLD with fibrosis, and 25 were CLD with cirrhosis. Total RNA was extracted from plasma followed by cDNA synthesis, and finally, the expression of miRNA-221 was analyzed for its diagnostic potential as a single biomarker using the qRT-PCR method. Results: The plasma level of miRNA-221 was significantly upregulated in different fibrosis stages of CLD (p < 0.05), and this upregulation was positively correlated with the progression of fibrosis (p < 0.05). Significantly increased expression of miRNA-221 was found in NAFLD patients compared to HBV patients in the CLD without fibrosis patient group (p < 0.05), while expression of miRNA-221 was significantly upregulated among HBV patients in the CLD with the fibrosis group. miRNA-221 showed high diagnostic accuracy in discriminating different stages of fibrosis from healthy control (p < 0.05). Conclusion: miRNA-221 may be used as a potential plasma biomarker for early prediction of fibrosis progression in CLD patients.
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  • 文章类型: Journal Article
    背景:由于疫苗接种和抗病毒治疗的改善,SARS-CoV-2感染的毒力和严重程度在普通人群中随着时间的推移而降低。肝硬化患者是否发生了类似的趋势尚不清楚。我们使用了国家COVID队列协作(N3C)来描述随着时间的推移的结果。
    方法:我们利用N3C3级数据集和未经审查的日期来识别截至2023年11月所有患有和不患有肝硬化的SARS-CoV-2感染的慢性肝病(CLD)患者。我们描述了按感染月观察到的30天病死率(CFR)。我们使用调整后的生存分析来计算与COVID-19大流行开始时的感染相比,按感染月份的相对死亡风险。
    结果:我们确定了在3/2020-11/2023之间感染SARS-CoV-2的总共117,811名CLD患者:27,428(23%)肝硬化和90,383(77%)无肝硬化。在整个研究期间观察到的30天CFRs为无肝硬化的CLD患者的1.1%(1,016)和肝硬化的6.3%(1,732)。在整个大流行期间,按感染月份观察到的30天CFR各不相同,自2022年以来呈持续下降趋势。与2020年第二季度(大流行开始时)的感染相比,2023年第3季度,无肝硬化的CLD患者在感染30日时的校正死亡风险为0.20(95CI0.08~0.50),有肝硬化的CLD患者为0.35(95CI0.18~0.69).
    结论:在这项N3C研究中,我们发现,观察到的30天CFR逐渐降低为CLD患者和无肝硬化,与普通人群中看到的更广泛的趋势一致。
    BACKGROUND: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time.
    METHODS: We utilized the N3C level 3 data set with uncensored dates to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared to infection at the onset of the COVID-19 pandemic.
    RESULTS: We identified 117,811 total CLD patients infected with SARS-CoV-2 between 3/2020-11/2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1,016) for CLD patients without cirrhosis and 6.3% (1,732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared to infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95%CI 0.08-0.50) for CLD patients without cirrhosis and 0.35 (95%CI 0.18-0.69) for CLD patients with cirrhosis.
    CONCLUSIONS: In this N3C study, we found that the observed 30-day CFR decreased progressively for both CLD patients with and without cirrhosis, consistent with broader trends seen in the general population.
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  • 文章类型: Journal Article
    组学技术和人工智能(AI)方法的进步正在推动我们在个性化诊断方面的进展,肝病学的预后和治疗策略。这篇综述提供了用于肝脏疾病组学数据分析的AI方法的当前景观的全面概述。我们概述了各种肝病中不同组学水平的患病率,以及对研究中使用的人工智能方法进行分类。具体来说,我们强调了转录组学和基因组谱的优势,以及对蛋白质组和甲基化组等其他水平的相对稀疏的探索,这代表了新见解的未开发潜力。公开可用的数据库倡议,如癌症基因组图谱和国际癌症基因组联盟为肝细胞癌的诊断和治疗的进步铺平了道路。然而,大型组学数据集的可用性对于其他肝脏疾病仍然有限.此外,应用复杂的AI方法来处理多组学数据集的复杂性需要大量数据来训练和验证模型,并且在实现具有临床实用性的无偏差结果方面面临挑战.讨论了解决数据匮乏和利用机会的策略。鉴于慢性肝病的全球负担巨大,必须建立多中心合作,以产生用于早期疾病识别和干预的大规模组学数据.探索先进的人工智能方法也是必要的,以最大限度地发挥这些数据集的潜力,并改善早期检测和个性化治疗策略。
    Advancements in omics technologies and artificial intelligence (AI) methodologies are fuelling our progress towards personalised diagnosis, prognosis and treatment strategies in hepatology. This review provides a comprehensive overview of the current landscape of AI methods used for analysis of omics data in liver diseases. We present an overview of the prevalence of different omics levels across various liver diseases, as well as categorise the AI methodology used across the studies. Specifically, we highlight the predominance of transcriptomic and genomic profiling and the relatively sparse exploration of other levels such as the proteome and methylome, which represent untapped potential for novel insights. Publicly available database initiatives such as The Cancer Genome Atlas and The International Cancer Genome Consortium have paved the way for advancements in the diagnosis and treatment of hepatocellular carcinoma. However, the same availability of large omics datasets remains limited for other liver diseases. Furthermore, the application of sophisticated AI methods to handle the complexities of multiomics datasets requires substantial data to train and validate the models and faces challenges in achieving bias-free results with clinical utility. Strategies to address the paucity of data and capitalise on opportunities are discussed. Given the substantial global burden of chronic liver diseases, it is imperative that multicentre collaborations be established to generate large-scale omics data for early disease recognition and intervention. Exploring advanced AI methods is also necessary to maximise the potential of these datasets and improve early detection and personalised treatment strategies.
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  • 文章类型: Journal Article
    腹部穿刺术是慢性肝病和腹水患者的诊断和治疗目的的常见程序。这篇综述旨在概述与腹腔穿刺术相关的出血风险的当前证据。使用PubMed进行电子搜索,MEDLINE,和OvidEMBASE从成立到2023年10月29日。如果他们检查了腹腔穿刺后出血的风险或减少慢性肝病患者出血的干预措施的疗效,则纳入研究。随机效应模型用于计算腹腔穿刺后出血事件的合并比例。异质性由I2、τ2统计量确定,和P值。纳入了8项研究进行审查。6项研究报告了腹部穿刺后出血事件。腹腔穿刺后出血事件的合并比例为0.32%(95%CI:0.15-0.69%)。这些研究中患者的术前INR和血小板计数的平均值介于1.4和2.0之间,以及50和153×109/L之间。分别。记录的最高INR为8.7,最低血小板计数为19×109/L。腹腔穿刺术后的大出血发生率为0-0.97%。两项研究表明,在慢性肝病患者穿刺前使用血栓弹力图(TEG)可识别出与手术相关的出血风险和输血需求减少的患者。慢性肝病和凝血病患者腹腔穿刺术后大出血的总体风险较低。TEG可用于预测出血风险和指导输血需求。
    Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post-abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random-effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I 2, τ2 statistics, and P-value. Eight studies were included for review. Six studies reported incident events of post-abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15-0.69%). The mean values for pre-procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0-0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure-related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements.
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