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Bariatric Surgery Reduced Long-Term Mortality in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Cirrhosis. 减肥手术降低了代谢功能障碍相关性脂肪肝和肝硬化患者的长期死亡率。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-14 DOI: 10.3350/cmh.2024.0564
Nicholas A Rouillard, Scott D Barnett, Xinrong Zhang, Leslie Kam, Richie Manikat, Ramsey Cheung, Mindie H Nguyen

Objective: With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the U.S.A. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.

Design: Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related, and non-liver-related mortality were analyzed.

Results: Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; P < 0.0001), liver-related (3.3% vs. 14%; P < 0.0001), and non-liver-related mortality (22.3% vs. 26.9%; P = 0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR] = 0.63; P < 0.0001), liver-related (aHR = 0.24; P < 0.0001), and non-liver-related (aHR = 0.81; P = 0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR = 0.39; P < 0.0001) whereas open surgeries were associated with higher overall mortality (aHR = 1.24; P = 0.022).

Conclusion: Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.

研究目的随着肥胖症的流行,代谢功能障碍相关性脂肪性肝病(MASLD)是美国最常见的肝病,也是终末期肝病和肝相关死亡的主要原因。因此,我们旨在比较接受和未接受减肥手术的代谢功能障碍相关性脂肪性肝病和肝硬化患者的长期预后:设计:我们从加利福尼亚州医疗保健访问和信息部的数据库中回顾性地识别了 2005 年至 2019 年的患者,进行了一项基于人群的队列研究。采用倾向评分匹配法(PSM)平衡接受减肥手术和未接受减肥手术的肝硬化患者的背景风险。研究分析了总死亡率、肝脏相关死亡率和非肝脏相关死亡率:在91708名符合条件的MASLD和肝硬化患者中,PSM得出了2107名接受减肥手术的患者和8428名未接受减肥手术的对照组患者。与匹配的对照组相比,接受减肥手术的患者5年总死亡率(24.9% vs. 37.1%;P < 0.0001)、肝脏相关死亡率(3.3% vs. 14%;P < 0.0001)和非肝脏相关死亡率(22.3% vs. 26.9%;P = 0.046)均较低。在多变量分析中,减肥手术与总死亡率(调整后危险比 [aHR] = 0.63;P < 0.0001)、肝脏相关死亡率(aHR = 0.24;P < 0.0001)和非肝脏相关死亡率(aHR = 0.81;P = 0.0026)的降低有关。然而,只有腹腔镜手术与较低的总死亡率相关(aHR = 0.39;P < 0.0001),而开腹手术与较高的总死亡率相关(aHR = 1.24;P = 0.022):结论:接受减肥手术(尤其是腹腔镜手术)的MASLD和肝硬化患者的死亡率明显低于未接受手术的患者。
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引用次数: 0
Prospect of emerging treatments for HBV functional cure. HBV 功能性治愈新疗法的前景。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-14 DOI: 10.3350/cmh.2024.0855
Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha (Peg-IFNα). Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides (ASOs) and small-interfering RNA (siRNAs) are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

功能性治愈是慢性乙型肝炎(CHB)的一个有利治疗终点,其定义是在停止治疗 24 周后,乙型肝炎表面抗原(HBsAg)血清清除持续且乙型肝炎病毒(HBV)DNA 无法量化。然而,目前的核苷酸类似物(NUC)和聚乙二醇干扰素α(Peg-IFNα)治疗方法很少能达到功能性治愈。目前正在开发多种新型病毒靶向药物和免疫调节剂来治疗 HBV,并将功能性治愈作为治疗目标。在病毒靶向药物中,反义寡核苷酸(ASOs)和小干扰 RNA(siRNAs)是目前最先进的研发方向,可诱导强效、持续的 HBsAg 抑制。其他病毒靶向药物因药物机制不同,对 HBsAg 和 HBV DNA 的作用也各不相同。相比之下,免疫调节剂对 HBsAg 的作用不大,在单一疗法中的作用有限。许多正在进行的临床试验研究了多种结合 RNA 干扰药和免疫调节剂的联合疗法。这些联合疗法在诱导功能性治愈方面显示出协同效应,很可能成为未来的发展方向。尽管取得了令人鼓舞的成果,但仍有必要开展研究,以优化治疗方案,并制定新型疗法后停用 NUC 的标准。功能性治愈现已成为慢性阻塞性肺病可实现的目标,新出现的新型疗法将彻底改变慢性阻塞性肺病的治疗。
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引用次数: 0
Correspondence to editorials on "Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial". 关于 "HK-660S 对原发性硬化性胆管炎患者的安全性和有效性:随机双盲2a期试验 "的社论。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0989
Woo Hyun Paik, Do Hyun Park
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引用次数: 0
Universal self-testing as a cost-effective weapon to eliminate hepatitis C virus in the Republic of Korea. 在大韩民国,普及自我检测是消除丙型肝炎病毒的一种具有成本效益的武器。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0992
Eun Sun Jang
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引用次数: 0
Correspondence to editorial on "Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma". 为 "用于预测肝内胆管癌预后的基质免疫特征的开发与验证 "的社论撰写通讯。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0998
Yu-Hang Ye, Shao-Lai Zhou
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引用次数: 0
Hepatitis E as a trigger for Acute-on-Chronic Liver Failure. 戊型肝炎是急性慢性肝衰竭的诱发因素。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0758
Maria Buti, Juan Carlos Ruiz-Cobo, Rafael Esteban, Mar Riveiro-Barciela

Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.

急性戊型肝炎病毒(HEV)感染通常具有自限性,预后良好。但是,某些人群,如已有慢性肝病的患者,可能会出现严重的表现,包括发展为急性-慢性肝功能衰竭(ACLF)。在各类病毒性肝炎中,甲型、戊型和乙型肝炎是导致急性慢性肝功能衰竭的主要原因。积极筛查和早期诊断肝硬化患者的 HEV 感染,尤其是出现 ACLF 的患者,可以改善管理并及时进行抗病毒治疗。预防措施,包括为高危人群接种戊型肝炎病毒疫苗,可以降低与戊型肝炎相关的发病率和死亡率。
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引用次数: 0
Reply to "Insights on Risk Score Development: Considerations for Early-Stage Hepatocellular Carcinoma Models". 对 "关于风险评分开发的见解:早期肝细胞癌模型的考虑因素"。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0999
Chun-Ting Ho, Elise Chia-Hui Tan, Chien-Wei Su
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引用次数: 0
Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment. 难以治疗的自身免疫性肝炎和原发性胆汁性胆管炎:药物治疗新时代的曙光。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0821
Atsumasa Komori, Yuki Kugiyama

Patients with hard-to-treat autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) are defined a posteriori as those who do not show a sufficient response or are intolerant to pharmacological treatments, thus not achieving biochemical surrogate endpoints that are associated with long-term liver-related-event-free survival. The absence of a recently harmonized definition of 'complete biochemical response within 6 months (CBR≤6M)', which is defined as the normalization of serum transaminase and IgG levels below the upper limit of normal (ULN) at ≤6 months after treatment initiation is regarded as hard-to-treat AIH. The implementation of CBR≤6M, in turn, has been facilitating clinical trials, e.g., between azathioprine and mycophenolate mofetil, to reconsider appropriate first-line steroid sparing agents, leading to a reduction in the number of hard-to-treat AIH cases. Regarding PBC, one of the disseminated definitions of hard-to-treat patients is the absence of POISE criteria, which are evaluated at 12 months with serum alkaline phosphatase and bilirubin levels, after the introduction of ursodeoxycholic acid. Hard-to-treat PBC not meeting the POISE criteria has very recently been the target population for the U.S. FDA-approved second-line drugs, elafibranor and seladelpar. In future pharmacological treatment of AIH and PBC, the primary objective for AIH is likely to focus on lowering the number of hard-to-treat patients with personalized steroid sparing treatment regimens. A challenging goal in PBC treatment is the further optimization of treatment surrogate endpoints, even to the stricter ALP normalization, with which an indication of second- or later-line drugs might be expanded, but could ultimately lengthen patients' long-term survival.

难以治疗的自身免疫性肝炎(AIH)或原发性胆汁性胆管炎(PBC)患者被事后定义为对药物治疗反应不充分或不耐受的患者,因此无法达到与长期无肝脏相关事件生存相关的生化替代终点。最近没有统一的 "6 个月内完全生化应答(CBR≤6M)"定义,即在开始治疗后≤6 个月内血清转氨酶和 IgG 水平正常化,低于正常上限(ULN),这被视为难以治疗的 AIH。CBR≤6M 的实施反过来又促进了临床试验,例如硫唑嘌呤和霉酚酸酯之间的试验,以重新考虑适当的一线类固醇疏导药物,从而减少了难以治疗的 AIH 病例数量。关于 PBC,对难治患者的一个广泛定义是不符合 POISE 标准,即在使用熊去氧胆酸后的 12 个月内通过血清碱性磷酸酶和胆红素水平进行评估。不符合 POISE 标准的难治性 PBC 患者最近已成为美国 FDA 批准的二线药物依来氟和塞拉得巴的目标人群。在未来的 AIH 和 PBC 药物治疗中,AIH 的主要目标可能是通过个性化的类固醇减量治疗方案减少难以治疗的患者人数。PBC 治疗的一个挑战性目标是进一步优化治疗代用终点,甚至是更严格的 ALP 正常化,这样可能会扩大二线或三线药物的适应症,但最终可能会延长患者的长期生存期。
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引用次数: 0
Letter to the Editor Clinical and Molecular Hepatology Correspondence on the Editorial regarding "The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients". 致编辑的信 临床与分子肝病学》杂志就 "使用瞬态弹性成像技术预测慢性乙型肝炎患者的肝细胞癌 "发表的社论进行通信。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.3350/cmh.2024.0994
Mirko Zoncapè, Emmanuel A Tsochatzis
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引用次数: 0
Stem cell exosomes: new hope and future potential for relieving liver fibrosis. 干细胞外泌体:缓解肝纤维化的新希望和未来潜力。
IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-07 DOI: 10.3350/cmh.2024.0854
Lihua Li, Yongjie Liu, Kunpeng Wang, Jinggang Mo, Zhiyong Weng, Hao Jiang, Chong Jin

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

肝纤维化是由病毒性肝炎、自身免疫性肝炎、非酒精性脂肪性肝炎、脂肪肝和胆汁淤积性肝病等因素引起的慢性肝损伤。肝移植是目前治疗严重肝病的金标准。然而,由于供体器官短缺以及必须终身接受免疫抑制治疗,肝移植受到了限制。间充质干细胞(MSCs)具有分化和增殖能力,移植到患者体内可分化成各种肝细胞,增强肝功能。因此,间充质干细胞可作为治疗肝病的替代疗法,特别是肝硬化、肝功能衰竭和肝移植并发症。然而,由于间充质干细胞具有潜在的致瘤作用,研究人员正在探索一种利用干细胞分泌的细胞外囊泡(外泌体)治疗肝纤维化的新方法。许多研究表明,干细胞释放的外泌体可通过各种途径促进肝损伤修复,有助于治疗肝纤维化。在这篇综述中,我们重点探讨干细胞外泌体通过不同途径影响肝纤维化的分子机制及其潜在治疗靶点。此外,我们还讨论了外泌体疗法相对于干细胞疗法的优势,以及外泌体研究的未来可能方向,包括临床应用前景和需要克服的挑战。
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引用次数: 0
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Clinical and Molecular Hepatology
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