Annals of hepatology最新文献_第2页

A comprehensive meta-analysis of stem cell therapy for liver failure: Assessing treatment efficacy and modality 干细胞治疗肝衰竭的综合荟萃分析：评估治疗效果和方式。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-16 DOI: 10.1016/j.aohep.2024.101586

Shenglong Lin , Haibing Gao , Huaxi Ma , Ziyuan Liao , Dongqing Zhang , Jinshui Pan , Yueyong Zhu

Introduction and Objectives

This meta-analysis aims to evaluate the efficacy of stem cell therapy (SCT) for liver failure.

Materials and Methods

The study adhered to the recommended guidelines of the PRISMA statement. Eligible studies published prior to May 13, 2023, were comprehensively searched in databases including PubMed, Web of Science, and Embase. Quality assessment was conducted using the Cochrane risk-of-bias tool, and the standard mean differences were calculated for the clinical parameters. The hazard ratios were determined by extracting individual patient data from the Kaplan-Meier curve.

Results

A total of 2,937 articles were retrieved, and eight studies were included in the final analysis. Most of the studies focused on HBV-related liver failure and were randomized controlled trials. All studies utilized mesenchymal stem cells (MSCs), with the majority (62.5%) being allogeneic. The analysis revealed that combining stem cell therapy with standard medical treatment or plasma exchange significantly enhanced patient survival and reduced MELD scores. Specifically, allogeneic stem cells showed superior efficacy in improving survival outcomes compared to autologous stem cells. Furthermore, deep vessel injection plus a single injection demonstrated better effectiveness than peripheral vessel injection plus multiple injections in reducing MELD scores.

Conclusions

This comprehensive analysis underscores the potential of MSC therapy in significantly improving survival and clinical outcomes in patients with liver failure, highlighting the superior benefits of allogeneic MSCs and deep vessel plus single injection administration.

引言与目的本荟萃分析旨在评估干细胞疗法（SCT）治疗肝衰竭的疗效。在PubMed、Web of Science和Embase等数据库中全面检索了2023年5月13日之前发表的符合条件的研究。使用 Cochrane 偏倚风险工具进行了质量评估，并计算了临床参数的标准平均差。结果共检索到 2,937 篇文章，最终分析纳入了 8 项研究。大部分研究侧重于 HBV 相关肝衰竭，并且是随机对照试验。所有研究都使用了间充质干细胞，其中大部分（62.5%）为异体干细胞。分析显示，干细胞疗法与标准药物治疗或血浆置换相结合，可显著提高患者存活率，降低MELD评分。具体而言，与自体干细胞相比，异体干细胞在改善生存结果方面表现出更优越的疗效。此外，在降低MELD评分方面，深部血管注射加单次注射比外周血管注射加多次注射显示出更好的疗效。

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引用次数: 0

A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response 墨西哥的肝硬化和移植情况：主要病因的变化和作为应对措施的移植。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-13 DOI: 10.1016/j.aohep.2024.101562

Icela Palma-Lara , María Guadalupe Ortiz-López , José Bonilla-Delgado , Juanita Pérez-Escobar , Ricardo Godínez-Aguilar , Claudia Luévano-Contreras , Ana María Espinosa-García , Javier Pérez-Durán , Patricia García Alonso-Themann , Manuel Nolasco-Quiroga , Javier Flores-Estrada , Paulina Carpinteyro-Espin , Daniel Juárez-Ascencio , Nayeli Goreti Nieto-Velazquez , Carmen Palacios-Reyes

Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 daily deaths due to these causes, and corresponds to the 4th or 5th place of all causes. The global prevalence of MASLD is estimated to affect 25% of the world's population, while in the pediatric population it could be higher. In Mexican population it is more prevalent since estimations were around 41.3% in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9%, with a mortality rate of 23.9%, primarily due to liver-related causes. In Mexico, ALD is present in 23% of all cirrhosis cases, already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due to programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as a response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.

肝硬化的病因包括酗酒、病毒感染（乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV））、酒精相关性肝病（ALD）和脂肪肝相关代谢功能障碍（MASLD）等。近年来，肝硬化的发病率有所上升，2017 年的发病率为每 10 万人 1395 例，死亡率为每 10 万人 18 例，相当于 147.2 万人死亡。在墨西哥，肝病是一个公共卫生问题，因为 2022 年有 41890 人死于肝病，其中包括肝硬化（>25000 人）和急性肝病（14927 人）。这意味着每天有 114 人死于这些病因，在所有病因中排名第 4 至第 5 位。据估计，MASLD 的全球发病率占世界总人口的 25%，而在儿童中的发病率可能更高。据估计，2023 年墨西哥人口的发病率将高达 41.3%。饮酒因其高发率和相关发病率而成为一个全球性健康问题，有 32.9% 的人与 ALD 有关，死亡率为 23.9%，主要是由于肝脏相关原因。在墨西哥，所有肝硬化病例中的 23% 都患有 ALD。在过去几年中，由于实施了筛查检测、疫苗和直接作用抗病毒药物计划，HCV 和 HBV 的发病率发生了变化。病因发生了转变，MASLD 增加，病毒性病因减少。为应对肝硬化病例的增加，有效的肝脏移植手术越来越多，包括最近授权的中心。这些努力是必要的，而预防策略则应根据主要病因来实施。

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引用次数: 0

Study on the prediction model of liver cancer based on chronic liver disease and the related molecular mechanism. 基于慢性肝病的肝癌预测模型及相关分子机制研究。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-13 DOI: 10.1016/j.aohep.2024.101572

Xiaojing Zhang, Xinye Chen

Introduction and objective: Due to the high heterogeneity of HCC, which leads to poor prognostic outcomes for patients, there is a need to develop a novel predictive model for accurate classification of HCC in order to improve patient survival rates.

Materials and methods: The data of the HCV, cirrhosis, and HCC were obtained from TCGA and GEO databases. Multivariable Cox regression analysis and survival analysis was conducted to assess the prognostic relevance of these differentially expressed genes. Single-cell sequencing was used to explore the intercellular interaction patterns and identify relevant signaling pathways. Drug sensitivity analysis was conducted to determine personalized treatment strategies for patients.

Results: In this study, we conducted integrated analysis of hepatitis, cirrhosis, and hepatocellular carcinoma datasets and identified 10 liver disease progression genes associated with prognosis. These genes exhibited significant downregulation in expression as the disease advanced, suggesting their crucial involvement in HCC development. By performing multivariable Cox analysis, we established a prognostic model for liver disease progression to predict the prognosis of HCC patients. The model was validated using ROC analysis, demonstrating good accuracy and stability in prognostic evaluation. Single-cell sequencing analysis revealed that these genes primarily exert their effects through the MIF signaling pathway during HCC progression. Furthermore, we observed that patients in the low-risk group exhibited higher sensitivity to TACE treatment, while patients in the high-risk group showed better response to sorafenib treatment.

Conclusions: In summary, we have elucidated the key genes involved in the progression of liver diseases and established a precise prognostic model for assessing the prognosis of HCC patients. Our study provides novel insights and strategies for the treatment of HCC.

导言和目的：由于 HCC 的高度异质性导致患者预后不良，因此需要开发一种新型预测模型对 HCC 进行准确分类，以提高患者的生存率：HCV、肝硬化和HCC的数据来自TCGA和GEO数据库。为评估这些差异表达基因的预后相关性，进行了多变量 Cox 回归分析和生存分析。单细胞测序被用于探索细胞间相互作用模式和识别相关信号通路。我们还进行了药物敏感性分析，以确定患者的个性化治疗策略：在这项研究中，我们对肝炎、肝硬化和肝细胞癌数据集进行了整合分析，发现了10个与预后相关的肝病进展基因。随着病情的发展，这些基因的表达出现了明显的下调，这表明它们在 HCC 的发展过程中起着至关重要的作用。通过多变量 Cox 分析，我们建立了一个肝病进展预后模型来预测 HCC 患者的预后。该模型经ROC分析验证，在预后评估中表现出良好的准确性和稳定性。单细胞测序分析表明，这些基因在 HCC 进展过程中主要通过 MIF 信号通路发挥作用。此外，我们还观察到低危组患者对TACE治疗的敏感性更高，而高危组患者对索拉非尼治疗的反应更好：总之，我们阐明了参与肝病进展的关键基因，并建立了评估 HCC 患者预后的精确预后模型。我们的研究为治疗 HCC 提供了新的见解和策略。

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引用次数: 0

Soft drink consumption and increased risk of nonalcoholic fatty liver disease: Results from the health workers cohort study 饮用软饮料与非酒精性脂肪肝风险的增加：卫生工作者队列研究的结果。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101566

Edgar Denova-Gutiérrez , Berenice Rivera-Paredez , Amado D. Quezada-Sánchez , Brianda I. Armenta-Guirado , Paloma Muñoz-Aguirre , Yvonne N. Flores , Rafael Velázquez-Cruz , Jorge Salmerón

Introduction and Objectives

Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition and an important public health problem. Some epidemiological studies have suggested that soft drinks (SD) intake is associated with NAFLD. However, the evidence is inconsistent. Our objective was to assess the association between SD consumption and the risk of NAFLD in a Mexican adult population.

Materials and Methods

A total of 1,759 participants from the Health Workers Cohort Study (HWCS) were included in the analyses. SD intake was measured using a validated food frequency questionnaire. We classified SD consumption as follows: a) less than 1 serving per week, b) 1 to less than 3.5 servings per week, and c) 3.5 or more servings per week. Hepatic steatosis index (HSI) was calculated based on sex, BMI, and blood transaminase levels, and was categorized as NAFLD ≥ 36. To assess the relation between SD and NAFLD, we followed two approaches: fixed effects logistic regression and generalized estimating equations.

Results

After adjusting for demographic characteristics, lifestyle factors, and dietary intake, the odds ratio (OR) and 95 % confidence interval (95 % CI) for NAFLD were 1.26 (95 % CI: 1.08, 1.48) for 1 to less than 3.5 servings per week and 1.42 (95 % CI: 1.19, 1.69) for ≥3.5 servings/week category in both sexes. When stratifying the analysis by sex, we observed that the association tended to be greater in men than in women.

Conclusions

The results from our prospective study indicate that SD consumption is associated with an increased risk of NAFLD.

导言和目标：非酒精性脂肪肝（NAFLD）是一种常见的临床疾病，也是一个重要的公共卫生问题。一些流行病学研究表明，软饮料（SD）摄入量与非酒精性脂肪肝有关。然而，相关证据并不一致。我们的目的是评估墨西哥成人非酒精性脂肪肝与软饮料摄入量之间的关系：共有 1,759 名来自卫生工作者队列研究（HWCS）的参与者参与了分析。SD摄入量通过有效的食物频率问卷进行测量。我们将 SD 摄入量分为以下几类：a) 每周少于 1 份；b) 每周 1 至少于 3.5 份；c) 每周 3.5 份或更多。根据性别、体重指数和血液转氨酶水平计算肝脏脂肪变性指数（HSI），并将其归类为非酒精性脂肪肝≥36。为了评估SD与非酒精性脂肪肝之间的关系，我们采用了两种方法：固定效应逻辑回归和广义估计方程：在对人口统计学特征、生活方式因素和饮食摄入量进行调整后，非酒精性脂肪肝的几率比（OR）和 95 % 置信区间（95 % CI）分别为：每周 1 至少于 3.5 份的男女为 1.26（95 % CI：1.03，1.55），每周≥3.5 份的男女为 1.42（95 % CI：1.15，1.74）。在按性别进行分层分析时，我们发现男性的相关性大于女性：我们的前瞻性研究结果表明，食用 SD 与非脂性脂肪肝风险的增加有关。

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引用次数: 0

EIF3B affects the invasion and metastasis of hepatocellular carcinoma cells via the TGFBI/MAPK/ERK pathway EIF3B 通过 TGFBI/MAPK/ERK 通路影响肝癌细胞的侵袭和转移。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101564

Ling Wang , Chuanzhong Huang , Wansong Lin , Zhifeng Zhou , Jieyu Li , Mingshui Chen , Lingyu Zhang , Yunbin Ye

Introduction and Objectives

To study the effect of eukaryotic initiation factor 3B (EIF3B) on the invasion and migration of hepatocellular carcinoma (HCC) and its potential mechanism.

Materials and Methods

The clinical significance of EIF3B expression was studied with The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interaction Analysis datasets. Immunohistochemical staining and western blotting were used to examine EIF3B expression in cell lines and tissues from HCC patients. The scratch assay and transwell assay were used to measure the invasion and metastasis of different HCC cell lines in vitro. The molecular mechanism of EIF3B was determined using RNA-seq and identification of dysregulated signaling pathways. Western blotting was used to verify the alterations of EIF3B signaling functioned in the promotion of HCC progression.

Results

Elevated expression of EIF3B in HCC correlated significantly with aggressive clinicopathologic characteristics, including advanced tumor grade and poor prognosis. Studies with cultured cells indicated that EIF3B knockdown inhibited HCC cell invasion and metastasis by depressing the epithelial-mesenchymal transition (EMT). EIF3B also activated the TGFBI/MAPK/ERK signaling pathway by increasing the levels of pMEK and pERK.

Conclusions

Our results indicate that EIF3B functions as an oncogene in HCC that accelerates cell invasion, metastasis, and the EMT by stimulation of the TGFBI/MAPK/ERK signaling pathway. EIF3B is a potential target for the treatment of HCC.

引言和目的：研究真核细胞启动因子 3B（EIF3B）对肝细胞癌（HCC）侵袭和迁移的影响及其潜在机制：研究真核细胞启动因子3B（EIF3B）对肝细胞癌（HCC）侵袭和迁移的影响及其潜在机制：通过癌症基因组图谱（TCGA）和基因表达谱分析数据集研究EIF3B表达的临床意义。免疫组化染色和免疫印迹技术用于检测 EIF3B 在细胞系和 HCC 患者组织中的表达。划痕试验和透孔试验用于测量不同 HCC 细胞株在体外的侵袭和转移。利用 RNA-seq 和识别失调信号通路确定 EIF3B 的分子机制。用 Western 印迹法验证了 EIF3B 信号改变在促进 HCC 进展中的作用：结果：EIF3B在HCC中的高表达与侵袭性临床病理特征显著相关，包括肿瘤分级晚和预后差。对培养细胞的研究表明，敲除 EIF3B 可抑制上皮-间质转化（EMT），从而抑制 HCC 细胞的侵袭和转移。EIF3B还通过提高pMEK和pERK的水平激活了TGFBI/MAPK/ERK信号通路：我们的研究结果表明，EIF3B 在 HCC 中发挥着癌基因的功能，它通过刺激 TGFBI/MAPK/ERK 信号通路加速细胞的侵袭、转移和 EMT。EIF3B 是治疗 HCC 的潜在靶点。

{"title":"EIF3B affects the invasion and metastasis of hepatocellular carcinoma cells via the TGFBI/MAPK/ERK pathway","authors":"Ling Wang , Chuanzhong Huang , Wansong Lin , Zhifeng Zhou , Jieyu Li , Mingshui Chen , Lingyu Zhang , Yunbin Ye","doi":"10.1016/j.aohep.2024.101564","DOIUrl":"10.1016/j.aohep.2024.101564","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>To study the effect of eukaryotic initiation factor 3B (EIF3B) on the invasion and migration of hepatocellular carcinoma (HCC) and its potential mechanism.</div></div><div><h3>Materials and Methods</h3><div>The clinical significance of EIF3B expression was studied with The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interaction Analysis datasets. Immunohistochemical staining and western blotting were used to examine EIF3B expression in cell lines and tissues from HCC patients. The scratch assay and transwell assay were used to measure the invasion and metastasis of different HCC cell lines <em>in vitro</em>. The molecular mechanism of EIF3B was determined using RNA-seq and identification of dysregulated signaling pathways. Western blotting was used to verify the alterations of EIF3B signaling functioned in the promotion of HCC progression.</div></div><div><h3>Results</h3><div>Elevated expression of EIF3B in HCC correlated significantly with aggressive clinicopathologic characteristics, including advanced tumor grade and poor prognosis. Studies with cultured cells indicated that <em>EIF3B</em> knockdown inhibited HCC cell invasion and metastasis by depressing the epithelial-mesenchymal transition (EMT). EIF3B also activated the TGFBI/MAPK/ERK signaling pathway by increasing the levels of pMEK and pERK.</div></div><div><h3>Conclusions</h3><div>Our results indicate that <em>EIF3B</em> functions as an oncogene in HCC that accelerates cell invasion, metastasis, and the EMT by stimulation of the TGFBI/MAPK/ERK signaling pathway. EIF3B is a potential target for the treatment of HCC.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101564"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of sleep patterns and disorders with metabolic dysfunction-associated steatotic liver disease and liver fibrosis in contemporary American adults 当代美国成年人的睡眠模式和失调与代谢功能障碍相关的脂肪肝和肝纤维化的关系

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101583

Guannan Zong , Wangjia Mao , Ming Wen , Xiaoyun Cheng , Guanghui Liu

Introduction and Objectives

The impact of sleep on metabolic dysfunction-associated steatotic liver disease (MASLD) in American adults remains unclear. This study aimed to address the relationship of sleep patterns and disorders with MASLD and liver fibrosis comprehensively.

Materials and Methods

This cross-sectional study included adult participants from the National Health and Nutrition Examination Survey 2017-2020. Multivariate adjusted regression analysis were used to examine the association of sleep with MASLD and liver fibrosis. We further addressed these associations using restricted cubic splines, mediation analysis, stratified analysis and multiple sensitivity analysis.

Results

We enrolled 5368 participants. Certain sleep disorders, sleep duration, high sleep debt and specific sleep-wake time were associated with MASLD. Late workday sleep was a shared risk factor for MASLD and liver fibrosis. Short sleep on workdays and free days favored MASLD, whereas average weekly long sleep protected against MASLD. Workday, free day and average weekly optimal sleep duration was 7.5 h, 8 h and 7.78 h, respectively. Mediation analysis suggested that fasting glucose and high-density lipoprotein cholesterol indirectly mediated the relationship between sleep duration and MASLD, whereas stratified analysis showed that sex influenced the relationship, and that the correlation was only observed in women and specific age groups.

Conclusions

Sleep duration independently affected MASLD but only in women and specific age groups. Moreover, late sleep on workdays was a shared risk factor for MASLD and liver fibrosis. These results suggest targeting sleep behaviors for MASLD prevention and developing age- and sex-specific strategies.

睡眠对美国成年人代谢功能障碍相关性脂肪肝（MASLD）的影响仍不清楚。本研究旨在全面探讨睡眠模式和失调与 MASLD 和肝纤维化的关系。这项横断面研究纳入了2017-2020年全国健康与营养调查的成年参与者。我们采用多变量调整回归分析来研究睡眠与MASLD和肝纤维化的关系。我们还使用限制性三次样条、中介分析、分层分析和多重敏感性分析进一步探讨了这些关联。我们共招募了 5368 名参与者。某些睡眠障碍、睡眠持续时间、高睡眠负债和特定睡眠-觉醒时间与 MASLD 相关。工作日晚睡是MASLD和肝纤维化的共同风险因素。工作日和空闲日的睡眠时间短有利于MASLD，而每周平均睡眠时间长则可预防MASLD。工作日、空闲日和每周平均最佳睡眠时间分别为7.5小时、8小时和7.78小时。中介分析表明，空腹血糖和高密度脂蛋白胆固醇间接中介了睡眠时间与MASLD之间的关系，而分层分析表明，性别影响了两者之间的关系，而且只有女性和特定年龄组的人群才观察到这种相关性。睡眠时间的长短会独立地影响 MASLD，但只有女性和特定年龄组的人才会受到影响。此外，工作日晚睡是MASLD和肝纤维化的共同风险因素。这些结果表明，应针对睡眠行为预防MASLD，并制定针对不同年龄和性别的策略。

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引用次数: 0

The Toulouse algorithm identifies patients with increased risk of cardiac decompensation only in patients with TIPS for refractory ascites 图卢兹算法只识别因难治性腹水而接受 TIPS 治疗的患者中心脏失代偿风险增加的患者。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101568

Emma Vanderschueren , Youri Bekhuis , Jan Clerick , Jappe Decock , Philippe Meersseman , Alexander Wilmer , Eveline Claus , Lawrence Bonne , Guido Claessen , Chris Verslype , Geert Maleux , Wim Laleman

Introduction and Objectives

TIPS placement is an effective, possibly life-saving, treatment for complications of portal hypertension. The pressure shift induced by the stent can lead to cardiac decompensation (CD). We investigated the incidence of CD, possible variables associated with CD and the validity of the Toulouse algorithm for risk prediction of CD post-TIPS.

Patients and Methods

A total of 106 patients receiving TIPS for variceal bleeding (VB, 41.5%) or refractory ascites (RA, 58.5%) with available echocardiography and NT-proBNP results were included and retrospectively reviewed. Development of CD between time of TIPS placement and occurrence of liver transplantation, death or loss-to-follow-up was recorded. Competing risk regression analysis was performed to assess which baseline variables predicted occurrence of CD post-TIPS.

Results

A total of 12 patients (11.3%) developed CD after a median of 11.5 days (IQR 4 to 56.5) post-TIPS. Multivariate regression showed age (HR 1.06, p = 0.019), albumin (HR 1.10, p = 0.009) and NT-proBNP (HR 1.00, p = 0.023) at baseline predicted CD in the RA group. No clear predictors were found in those receiving TIPS for VB. Correspondingly, the Toulouse algorithm successfully identified patients at risk for CD, however only in the RA population (zero risk 0% vs. low risk 12.5% vs. high risk 35.3% with CD; p = 0.003).

Conclusions

CD is not an infrequent complication post-TIPS occurring in 1/10 patients. The Toulouse algorithm can identify patients at risk of CD, though only in patients receiving TIPS for RA. Allocation to the high-risk category warrants close monitoring but should not preclude TIPS placement.

导言和目的：TIPS 置入术是治疗门静脉高压并发症的有效方法，也可能是挽救生命的方法。支架引起的压力转移可导致心脏失代偿（CD）。我们调查了 CD 的发生率、与 CD 相关的可能变量以及 TIPS 术后 CD 风险预测图卢兹算法的有效性：共纳入 106 名因静脉曲张出血（VB，41.5%）或难治性腹水（RA，58.5%）而接受 TIPS 的患者，并对其超声心动图和 NT-proBNP 结果进行回顾性分析。记录了从放置 TIPS 到发生肝移植、死亡或失去随访期间 CD 的发展情况。进行了竞争风险回归分析，以评估哪些基线变量可预测TIPS术后CD的发生：共有12名患者（11.3%）在TIPS术后中位11.5天（IQR为4-56.5）后出现CD。多变量回归显示，年龄（HR 1.06，p = 0.019）、白蛋白（HR 1.10，p = 0.009）和基线时的 NT-proBNP（HR 1.00，p = 0.023）可预测 RA 组的 CD。在因 VB 而接受 TIPS 的患者中未发现明确的预测因素。相应地，图卢兹算法成功识别了CD风险患者，但仅限于RA人群（零风险0% vs. 低风险12.5% vs. 高风险35.3%有CD；p = 0.003）：结论：CD并非TIPS术后的罕见并发症，1/10的患者会出现CD。图卢兹算法可以识别有 CD 风险的患者，但仅限于接受 TIPS 治疗的 RA 患者。被归入高风险类别的患者需要密切监测，但不应排除 TIPS 置入。

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引用次数: 0

Gilberta Bensabath – Centenary of the discoverer of the high prevalence of hepatitis B and Delta in the Amazon – On the path to elimination as a public health problem! 吉尔伯塔-本萨巴斯（Gilberta Bensabath）--亚马逊地区乙型肝炎和三角洲肝炎高发病率发现者一百周年--在消除这一公共卫生问题的道路上！

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101575

João Renato Rebello Pinho, Michele Gomes-Gouvêa, Flair José Carrilho

引用次数: 0

Ethanol with thioacetamide murine model of alcoholic liver disease identifies hepatic pathways as targets for the human disease 乙醇与硫代乙酰胺的酒精性肝病小鼠模型确定了作为人类疾病靶点的肝脏通路。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101565

Ashi Mittal , Nishu Choudhary , Sudrishti Chaudhary , Anupama Kumari , Archana Rastogi , Guresh Kumar , Jaswinder Singh Maras , Shiv K Sarin , Shvetank Sharma

Introduction and Objectives

Hepatic proteome and gut microbiota alterations are known in alcohol-associated hepatitis (AAH). Current animal models sparsely mimic human AAH. We aimed to develop an murine model that closely resembled human AAH.

Materials and Methods

Male C57BL/6N mice were pair-fed control/incremental ethanol Lieber-DeCarli diets and thioacetamide (TAA) for 12-weeks to induce AAH. Hepatic proteome was analyzed using LC-MS/MS. Gut-bacteria was determined using 16s-rRNA sequencing.

Results

Mice exposed to EtOH+TAA displayed higher expression of liver triglycerides (1.5-fold, p = 0.001), pro-inflammatory (IL6, 1.5-fold, p = 0.002 and TNFα, 1.7-fold, p = 0.01), fibrotic (TGF-β, 2.7-fold, p = 0.01 and Col1α1, 2-fold, p = 0.01) and oxidative markers (GSH and SOD (-1.5 fold, p = 0.004 & 0.005 respectively)) as compared to EtOH alone. Histology of EtOH+TAA liver displayed pericellular liver fibrosis, increased steatosis, and neutrophil infiltration, which resembled human AAH. In the 12wk EtOH+TAA group, Desulfobacteria, Campylobacteria, and Patescibacteria increased by 2-fold (p = 0.02). Pathway combined score (CS, log10) in EtOH+TAA treatment showed upregulated hepatic ethanol oxidation (CS=1.93), fatty acid biosynthesis (CS=2.48), necrosis (CS=1.59), collagen formation (CS=1.28) and hypoxia (CS=0.68) and downregulated fatty acid beta-oxidation (CS=2.37), PPAR signaling (CS=1.35) fatty acid degradation (CS=2.35), bile acid metabolism (CS=1.87), and oxidative phosphorylation (CS=1.50), as observed in human disease.

Conclusions

Using an ethanol-thioacetamide combination in mice results in a faster establishment of AAH with fibrosis than previously known models. Differential protein expression strongly correlates with pathways found altered in human AAH, thus making the model mimic human disease better than other known models., respectively. Thioacetamide (TAA) was administered to enhance liver fibrosis and mimic human AAH.

引言和目的：已知酒精相关性肝炎（AAH）会引起肝脏蛋白质组和肠道微生物群的改变。目前的动物模型很少模拟人类 AAH。我们的目标是建立一个与人类 AAH 非常相似的小鼠模型：雄性 C57BL/6N 小鼠被配对喂食对照组/增量乙醇 Lieber-DeCarli 日粮和硫代乙酰胺（TAA）12 周，以诱导 AAH。使用 LC-MS/MS 分析肝脏蛋白质组。利用 16s-rRNA 测序确定肠道细菌：结果：暴露于 EtOH+TAA 的小鼠肝脏甘油三酯（1.5 倍，p = 0.001）、促炎性（IL6，1.5 倍，p = 0.002 和 TNFα，1.7 倍，p = 0.01）、纤维化（TGF-β，2.7 倍，p = 0.01 和 Col1α1，2 倍，p = 0.01）和氧化标志物（GSH 和 SOD（-1.5 倍，p = 0.004 和 0.005））。EtOH+TAA肝脏的组织学表现为肝纤维化、脂肪变性和中性粒细胞浸润，与人类AAH相似。在 12 周的 EtOH+TAA 组中，脱硫杆菌、弯曲杆菌和棒状杆菌增加了 2 倍（p = 0.02）。EtOH+TAA处理的通路综合得分（CS，log10）显示，肝脏乙醇氧化（CS=1.93）、脂肪酸生物合成（CS=2.48）、坏死（CS=1.59）、胶原形成（CS=1.28）和缺氧（CS=0.68），并下调脂肪酸β-氧化（CS=2.37）、PPAR 信号转导（CS=1.35）、脂肪酸降解（CS=2.35）、胆汁酸代谢（CS=1.87）和氧化磷酸化（CS=1.50），正如在人类疾病中观察到的那样：结论：与之前已知的模型相比，在小鼠体内使用乙醇-硫代乙酰胺组合可更快地形成伴有纤维化的 AAH。差异蛋白表达与人类 AAH 中发现的改变途径密切相关，因此该模型比其他已知模型更能模拟人类疾病。硫代乙酰胺（TAA）可增强肝纤维化并模拟人类 AAH。

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引用次数: 0

Camrelizumab combined with transcatheter arterial chemoembolization and sorafenib or lenvatinib for unresectable hepatocellular carcinoma: A multicenter, retrospective study 康瑞珠单抗联合经导管动脉化疗栓塞术、索拉非尼或来伐替尼治疗不可切除肝细胞癌：一项多中心回顾性研究。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2024-09-12 DOI: 10.1016/j.aohep.2024.101578

Xiumei Jiang , Pan Wang , Ke Su , Han Li , Hao Chi , Fei Wang , Yu Liu , Ke Xu

Introduction and Objectives

We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC).

Materials and Methods

From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups.

Results

Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055).

Conclusions

Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

简介和目的：我们发起了这项研究，以探讨康瑞珠单抗联合经导管动脉化疗栓塞（TACE）加索拉非尼或来伐替尼与TACE加索拉非尼或来伐替尼治疗不可切除肝细胞癌（HCC）的疗效：本研究对2019年6月至2022年11月的127例晚期HCC患者进行了回顾性分析。其中包括44例接受康瑞珠单抗+TACE+索拉非尼或来伐替尼治疗的患者（三联治疗组）和83例接受TACE+索拉非尼或来伐替尼治疗的患者（双联治疗组）。比较了两组患者的总生存期（OS）、无进展生存期（PFS）、客观反应率（ORR）和疾病控制率（DCR）：结果：我们的研究结果表明，接受三联疗法的患者的中位OS（15.8个月 vs. 10.3个月，P=0.0011）和中位PFS（7.2个月 vs. 5.2个月，P=0.019）均优于双联疗法组。此外，三联疗法组的 6 个月生存率（93.5% 对 66.3%）、12 个月生存率（67.2% 对 36.3%）和 24 个月生存率（17.2% 对 7.6%）均优于双联疗法组。不过，两组的ORR（43.2% vs. 28.9%，P = 0.106）和DCR（93.2% vs. 81.9%，P = 0.084）相似。亚组分析显示，与双重治疗组相比，三联治疗组对伴有HBV的HCC（15.8个月 vs. 9.6个月，P = 0.0015）和肿瘤直径≥5cm的HCC（15.3个月 vs. 9.6个月，P = 0.00055）的mOS更好：结论：卡瑞珠单抗联合TACE、索拉非尼或来伐替尼可能是临床治疗不可切除的HCC患者的一种很有前景的治疗方法。

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