Livers最新文献_第2页

Autoimmune Hepatitis Management: Recent Advances and Future Prospects 自身免疫性肝炎管理：最新进展与未来展望

Livers

Pub Date : 2024-05-15 DOI: 10.3390/livers4020017

Rebeca Sierra, Ana Marenco-Flores, Marwan Alsaqa, R. Barba, Marcela Cuellar-Lobo, Carla Barberan, Leandro Sierra

Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments.

自身免疫性肝炎（AIH）是一种多种多样的炎症性慢性肝病。自身免疫性肝炎的发病率各不相同，近来有所上升。诊断需要通过肝活检和血清学检测发现组织学特征。临床特征各不相同，多达 40% 的患者可能没有症状。治疗前评估硫嘌呤甲基转移酶（TMPM）的活性对获得最佳反应至关重要。主要治疗目标是生化缓解、血清 IgG 和肝酶正常化。诱导治疗通常包括硫唑嘌呤和皮质类固醇。密切监测肝功能检查和血清免疫球蛋白水平至关重要。在达到生化缓解后，可逐渐减少用药。难治性疾病或肝硬化可能需要肝移植。需要进一步的治疗方法，尤其是对一线治疗无效者。

引用次数: 0

Validation and Comparison of Non-Invasive Tests for the Exclusion of High-Risk Varices in Compensated Advanced Chronic Liver Disease 用于排除慢性肝病晚期患者高风险静脉曲张的非侵入性检验的验证与比较

Livers

Pub Date : 2024-04-12 DOI: 10.3390/livers4020014

Rajiv Kurup, E. Kalo, S. Read, Wai-See Ma, Jacob George, G. Ahlenstiel

(Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD.

(无创检查（NIT）是食管胃十二指肠镜检查（OGD）的潜在替代方法，可用于排除代偿性晚期慢性肝病（cACLD）患者的高危静脉曲张（HRV）。这项回顾性研究旨在对澳大利亚多中心队列中的各种 NIT 进行外部验证和比较。cACLD 患者于 2013 年 1 月至 2022 年 12 月间入组。研究收集了肝脏硬度测量值（LSM）、临床病理数据和OGD结果。共纳入 210 名患者。中位年龄为57岁，65.7%为男性。cACLD 的主要病因是丙型肝炎（41.9%），91.9% 的患者为 Child-Pugh A 型。在所有病因的 cACLD 患者中，只有巴韦诺 VI 标准（B6C）可以安全地减少对 OGD 的需求，其阴性预测值为 98.6，33.8% 的患者无需进行 OGD。FIB-4可避免最多的OGD（71%）；但HRV漏检率为6%。结果表明，在我们的队列中，B6C 是性能最好的 NIT，无论病因如何，它都能可靠地排除 cACLD 患者的心率变异。这项研究证实，Baveno VI 标准可用于澳大利亚的混合病因队列，以避免不必要的 OGD 筛查。

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引用次数: 0

Serendipity in Medicine-Elevated Immunoglobulin E Levels Associated with Excess Alcohol Consumption 医学中的偶然性--免疫球蛋白 E 水平升高与过量饮酒有关

Livers

Pub Date : 2024-03-25 DOI: 10.3390/livers4020012

Stephen D. H. Malnick, Ali Abdullah, Fadi Ghanem, Sheral Ohayon Michael, Manuela G. Neuman

Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The first-year resident who admitted the patient mistakenly ordered a blood test for serum IgE. The result was a markedly elevated −6440 IU/mL. There was no evidence of parasitic infections, atopy or autoimmune disease nor was there any eosinophilia. A literature search showed that elevated IgE levels are associated with alcohol abuse. This association has been forgotten and does not appear in standard reference sources such as UptoDate or Harrison’s Principles of Internal Medicine. This judicious use of examining serum IgE levels may aid in the diagnosis of alcoholic hepatitis.

诊断酒精性肝病并非易事。在获得准确可靠的饮酒史方面存在问题。实验室检查结果和肝脏成像检查既不敏感也不特异，目前正在考虑采用更新的检查方法。最近，一名患者因可能患有酒精性肝炎而入院。收治该患者的一年级住院医师错误地要求进行血清 IgE 血液检测。结果显示血清 IgE 明显升高至 -6440 IU/mL。没有寄生虫感染、过敏或自身免疫性疾病的证据，也没有嗜酸性粒细胞增多。文献检索显示，IgE 水平升高与酗酒有关。这种关联已被遗忘，也未出现在标准参考资料中，如《UptoDate》或《Harrison's Principles of Internal Medicine》。明智地使用血清 IgE 水平检查有助于酒精性肝炎的诊断。

引用次数: 0

Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma 热休克蛋白在肝细胞癌中的功能和治疗用途

Livers

Pub Date : 2024-03-04 DOI: 10.3390/livers4010011

Ramakrushna Paul, Smriti Shreya, Shweta Pandey, Srishti Shriya, Aya Abou Hammoud, Christophe F Grosset, Buddhi Prakash Jain

Heat shock proteins are intracellular proteins expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role in regulating cell cycle and cell death, work as molecular chaperons during the folding of newly synthesized proteins, and also in the degradation of misfolded proteins. They are not only produced under stress conditions like acidosis, energy depletion, and oxidative stress but are also continuously synthesized as a result of their housekeeping functions. There are different heat shock protein families based on their molecular weight, like HSP70, HSP90, HSP60, HSP27, HSP40, etc. Heat shock proteins are involved in many cancers, particularly hepatocellular carcinoma, the main primary tumor of the liver in adults. Their deregulations in hepatocellular carcinoma are associated with metastasis, angiogenesis, cell invasion, and cell proliferation and upregulated heat shock proteins can be used as either diagnostic or prognostic markers. Targeting heat shock proteins is a relevant strategy for the treatment of patients with liver cancer. In this review, we provide insights into heat shock proteins and heat shock protein-like proteins (clusterin) in the progression of hepatocellular carcinoma and their use as therapeutic targets.

热休克蛋白是原核细胞和真核细胞中表达的细胞内蛋白质，有助于保护细胞免受压力。它们在调节细胞周期和细胞死亡方面发挥着重要作用，在新合成蛋白质的折叠过程中充当分子伴侣，还能降解折叠错误的蛋白质。热休克蛋白不仅在酸中毒、能量耗竭和氧化应激等应激条件下产生，而且由于其内务功能而不断合成。根据分子量的不同，热休克蛋白有不同的家族，如 HSP70、HSP90、HSP60、HSP27、HSP40 等。热休克蛋白与许多癌症有关，尤其是肝细胞癌，它是成人肝脏的主要原发性肿瘤。肝细胞癌中热休克蛋白的失调与转移、血管生成、细胞侵袭和细胞增殖有关，上调的热休克蛋白可用作诊断或预后标志物。靶向热休克蛋白是治疗肝癌患者的一种相关策略。在这篇综述中，我们将深入探讨热休克蛋白和热休克蛋白样蛋白（集群蛋白）在肝细胞癌进展过程中的作用，以及它们作为治疗靶点的用途。

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引用次数: 0

Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose. 对乙酰氨基酚过量后，腺苷 A2B 受体向线粒体的转移会影响细胞色素 P450 2E1 的活性。

Livers

Pub Date : 2024-03-01 Epub Date: 2023-12-26 DOI: 10.3390/livers4010002

Giselle Sanchez-Guerrero, David S Umbaugh, Abhay A Ramachandran, Antonio Artigues, Hartmut Jaeschke, Anup Ramachandran

The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.

腺苷 A2B 受体（A2BAR）是 G 蛋白偶联受体（GPCR）家族中的一员，它对腺苷的亲和力较低，目前与多种病理生理状况有关。我们已经证明了激活 A2BAR 对促进对乙酰氨基酚（APAP）过量引起的急性肝损伤后的恢复有好处。虽然细胞内的受体转运被认为在 GPCR 信号转导中发挥作用，但其在 APAP 诱导的肝损伤中调解 A2BAR 效应的作用却不甚明了。本文对这一问题进行了研究，对 C57BL/6J 小鼠施以过量的 APAP（300 毫克/千克），并对 A2BAR 细胞内定位的时间过程进行了研究。通过使用 A2BAR 激动剂 BAY 60-6583 或拮抗剂 PSB 603，研究了 A2BAR 激活或抑制对贩运的影响。通过使用 4-甲基吡唑（4-methylpyrazole，一种 Cyp2E1 和 JNK 激活抑制剂）探讨了 APAP 诱导的细胞信号传导对 A2BAR 运输的调节作用。我们的结果表明，APAP 过量会诱导 A2BAR 转位至线粒体，而 4MP 可阻止这种转运。此外，我们还证明了 A2BAR 定位于线粒体外膜，并与孕酮受体膜成分 1（PGRMC1）相互作用。激活 A2BAR 会增强线粒体的定位，而抑制 A2BAR 则会降低 PGRMC1 的线粒体水平并减弱线粒体 Cyp2E1 的活性。因此，我们的数据揭示了迄今为止尚未认识到的 A2BAR 向线粒体迁移及其与 PGRMC1 相互作用的结果，PGRMC1 可调节线粒体 Cyp2E1 的活性并调节 APAP 诱导的肝损伤。

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引用次数: 0

Resmetirom: Finally, the Light at the End of the NASH Tunnel? Resmetirom：NASH隧道尽头的曙光终于出现了吗？

Livers

Pub Date : 2024-02-26 DOI: 10.3390/livers4010010

A. Lonardo

Nonalcoholic steatohepatitis (NASH) is a double composite word that was first coined in 1980 by Ludwig and Colleagues [...]

非酒精性脂肪性肝炎（NASH）是一个双重复合词，由路德维希及其同事于 1980 年首次创造 [...] 。

引用次数: 0

Minimally Invasive Surgery in Liver Transplantation: From Living Liver Donation to Graft Implantation 肝移植中的微创手术：从活体肝脏捐献到移植物植入

Livers

Pub Date : 2024-02-17 DOI: 10.3390/livers4010009

E. Avramidou, Konstantinos Terlemes, Afroditi Lymperopoulou, Georgios Katsanos, Nikolaos Antoniadis, Athanasios Kofinas, S. Vasileiadou, Konstantina-Eleni Karakasi, Georgios Tsoulfas

Since the end of the 20th century and the establishment of minimally invasive techniques, they have become the preferred operative method by many surgeons. These techniques were applied to liver surgery for the first time in 1991, while as far as transplantation is concerned their application was limited to the living donor procedure. We performed a review of the literature by searching in Pubmed and Scopus using the following keywords: Liver transplantation, Minimally invasive surgery(MIS) living liver donor surgery. Applications of MIS are recorded in surgeries involving the donor and the recipient. Regarding the recipient surgeries, the reports are limited to 25 patients, including combinations of laparoscopic, robotic and open techniques, while in the living donor surgery, the reports are much more numerous and with larger series of patients. Shorter hospitalization times and less blood loss are recorded, especially in centers with experience in a large number of cases. Regarding the living donor surgery, MIS follows the same principles as a conventional hepatectomy and is already the method of choice in many specialized centers. Regarding the recipient surgery, significant questions arise mainly concerning the safe handling of the liver graft.

自 20 世纪末微创技术问世以来，微创技术已成为许多外科医生的首选手术方法。1991年，这些技术首次应用于肝脏手术，但就移植而言，其应用仅限于活体捐献手术。我们使用以下关键词在 Pubmed 和 Scopus 上进行了文献检索：肝移植、微创手术（MIS）、活体肝脏捐献手术。微创手术在涉及供体和受体的手术中均有应用记录。关于受体手术的报道仅限于25名患者，包括腹腔镜、机器人和开腹技术的组合，而关于活体肝脏捐献手术的报道则更多，患者人数也更多。有记录显示，住院时间更短，失血量更少，尤其是在有大量病例经验的中心。关于活体供体手术，MIS 遵循的原则与传统肝切除术相同，已成为许多专业中心的首选方法。关于受体手术，出现的重要问题主要涉及肝脏移植物的安全处理。

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引用次数: 0

Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature 草药和膳食补充剂诱发的肝损伤：最新文献综述

Livers

Pub Date : 2024-02-13 DOI: 10.3390/livers4010008

Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.

由于草药补充剂以及补充和替代药物的不断普及，草药诱发肝损伤（HILI）的发病率逐年上升。我们对 2021 年 3 月至 2023 年 3 月期间发表的病例报告和临床研究进行了详细的文献综述。我们讨论了 HILI 的流行病学和诊断，以及现行和拟议的法律法规。我们讨论了 2021 年 ACG 指南和 2022 年 AASLD 实践指南中关于药物和草药引起的肝损伤的诊断和管理。我们介绍了以前报道过的 HILI 病因的最新情况，如阿育吠陀、灰树精、姜黄、桔梗、绿茶提取物和藤黄。此外，还介绍了导致 HILI 的新描述的保健品，如洋金花、七叶树、碱性水等。我们讨论了在动物模型和人类肝细胞研究中新发现和以前发现的保肝草药补充剂。本综述认为，有必要对肝损伤的原因和机制进行持续研究，以确保将来能对其进行正确的诊断、预防和治疗。本综述旨在为新手和专家读者提供有关 HILI 可能病因的知识和总体概述。

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引用次数: 0

Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature 草药和膳食补充剂诱发的肝损伤：最新文献综述

Livers

Pub Date : 2024-02-13 DOI: 10.3390/livers4010008

Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.

由于草药补充剂以及补充和替代药物的不断普及，草药诱发肝损伤（HILI）的发病率逐年上升。我们对 2021 年 3 月至 2023 年 3 月期间发表的病例报告和临床研究进行了详细的文献综述。我们讨论了 HILI 的流行病学和诊断，以及现行和拟议的法律法规。我们讨论了 2021 年 ACG 指南和 2022 年 AASLD 实践指南中关于药物和草药引起的肝损伤的诊断和管理。我们介绍了以前报道过的 HILI 病因的最新情况，如阿育吠陀、灰树精、姜黄、桔梗、绿茶提取物和藤黄。此外，还介绍了导致 HILI 的新描述的保健品，如洋金花、七叶树、碱性水等。我们讨论了在动物模型和人类肝细胞研究中新发现和以前发现的保肝草药补充剂。本综述认为，有必要对肝损伤的原因和机制进行持续研究，以确保将来能对其进行正确的诊断、预防和治疗。本综述旨在为新手和专家读者提供有关 HILI 可能病因的知识和总体概述。

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引用次数: 0

High-Dose Acetaminophen as a Treatment for Cancer 大剂量对乙酰氨基酚治疗癌症

Livers

Pub Date : 2024-01-31 DOI: 10.3390/livers4010007

Jeffrey Wu, Bradley Maller, Rujul Kaul, Andrea Galabow, A. Bryan, Alexander Neuwelt

The use of high-dose acetaminophen (AAP) with n-acetylcysteine (NAC) rescue was studied as an anti-cancer treatment in phase I trials with promising signals of anti-tumor efficacy. Correlative analysis suggested that AAP has a free-radical-independent mechanism of anti-tumor activity—in contrast to the well-established mechanism of AAP hepatotoxicity. Subsequent “reverse translational” studies in the pre-clinical setting have identified novel mechanisms of action of high-dose AAP, including modulation of JAK-STAT signaling in both the tumor cell and the tumor immune microenvironment. Importantly, these effects are free-radical-independent and not reversed by concurrent administration of the established AAP rescue agents fomepizole and NAC. By administering high-dose AAP concurrently with fomepizole and NAC, 100-fold higher AAP levels than those of standard dosing can be achieved in mice without detected toxicity and with substantial anti-tumor efficacy against commonly used mouse models of lung and breast cancer that are resistant to standard first-line anti-cancer therapies. With these recent advances, additional clinical trials of high-dose AAP with concurrent NAC and fomepizole-based rescue are warranted.

在 I 期试验中，研究人员将大剂量对乙酰氨基酚（AAP）与正乙酰半胱氨酸（NAC）一起作为抗癌治疗方法，结果显示抗肿瘤效果很好。相关分析表明，AAP 具有不依赖自由基的抗肿瘤活性机制，这与 AAP 肝毒性的既定机制形成鲜明对比。随后在临床前环境中进行的 "逆向转化 "研究发现了大剂量 AAP 的新作用机制，包括调节肿瘤细胞和肿瘤免疫微环境中的 JAK-STAT 信号。重要的是，这些作用与自由基无关，而且不会因同时服用已确立的AAP解救药福美吡唑和NAC而逆转。在给小鼠注射高剂量 AAP 的同时注射福美吡唑和 NAC，可使小鼠体内的 AAP 水平比标准剂量高出 100 倍，而不会检测到毒性，并且对常用的肺癌和乳腺癌小鼠模型具有显著的抗肿瘤疗效，这些模型对标准的一线抗癌疗法具有抗药性。有了这些最新进展，有必要对同时使用 NAC 和福美唑类救治药物的高剂量 AAP 进行更多临床试验。

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引用次数: 0