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Therapeutic Potential of Human Microbiome-Based Short-Chain Fatty Acids and Bile Acids in Liver Disease 基于微生物群的短链脂肪酸和胆汁酸在肝病中的治疗潜力
Pub Date : 2022-08-03 DOI: 10.3390/livers2030012
Raja Ganesan, K. Suk
Microbiome-derived short chain fatty acids (SCFAs: acetate, propionate, and butyrate) and bile acids (BAs: primary BAs and secondary BAs) widely influence liver metabolic inflammation, immune responses, and carcinogenesis. In recent literature, the role of SCFAs and BAs in various liver diseases has been discussed. SCFAs and BAs are two types of microbiome-derived metabolites and they have been shown to have immunoregulatory ability in autoimmunity, inflammation, and liver-cancer microcellular environments. SCFAs and BAs are dependent on dietary components. The numerous regulatory processes in lymphocytes and non-immune cells that underpin both the positive and harmful effects of microbial metabolites include variations in metabolic signaling and epigenetic states. As a result, histone deacetylase (HDAC) inhibitors, SCFAs, and BAs, which are powerful immunometabolism modulators, have been explored. BAs have also been shown to alter the microbiome as well as adaptive and innate immune systems. We therefore emphasize the important metabolites in liver disease for clinical therapeutic applications. A deep understanding of SCFAs and Bas, as well as their molecular risk, could reveal more about certain liver-disease conditions.
微生物组衍生的短链脂肪酸(SCFAs:乙酸盐、丙酸盐和丁酸盐)和胆汁酸(BAs:原发性BAs和继发性BAs)广泛影响肝脏代谢炎症、免疫反应和致癌作用。在最近的文献中,SCFAs和BAs在各种肝脏疾病中的作用已经得到了讨论。SCFA和BA是两种微生物衍生的代谢产物,它们已被证明在自身免疫、炎症和肝癌微细胞环境中具有免疫调节能力。SCFA和BA依赖于膳食成分。淋巴细胞和非免疫细胞中的许多调节过程支持微生物代谢产物的积极和有害影响,包括代谢信号和表观遗传状态的变化。因此,组蛋白去乙酰化酶(HDAC)抑制剂、SCFAs和BA,作为强大的免疫代谢调节剂,已经得到了探索。BA也被证明可以改变微生物组以及适应性和先天免疫系统。因此,我们强调肝病中重要的代谢产物在临床治疗中的应用。对SCFA和Bas及其分子风险的深入了解可以揭示更多关于某些肝病的信息。
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引用次数: 6
A Comprehensive Review on the Use of Herbal Dietary Supplements in the USA, Reasons for Their Use, and Review of Potential Hepatotoxicity 在美国使用草药膳食补充剂的综合综述,其使用的原因,并审查潜在的肝毒性
Pub Date : 2022-08-02 DOI: 10.3390/livers2030011
Adnan Khan, Kashyap Chauhan, Heather Ross, N. Parra, John Magagna, Makala Wang, Patrick Zhu, Ryan Erwin, D. Halegoua-DeMarzio
Herbal and dietary supplement (HDS) use has grown exponentially in the United States. Unfortunately, the incidence of HDS-related liver injury has proportionally increased. Despite the potential for certain HDSs to cause clinically significant liver injury, they are not regulated by the Food and Drug Administration. Recent efforts have been made to regulate HDSs but are far removed from the scrutiny of prescription medications. Scant literature exists on HDSs and their risks of causing liver injury. In this comprehensive review, we examine trends of HDS use in the United States and the pathophysiologic mechanisms of drug-induced liver injury (DILI) of certain HDSs. Finally, we review usage rates; benefits, if any; purported pathophysiology of DILI; and propensity for progression to fulminant hepatic failure of nine HDSs linked to clinically significant DILI.
草药和膳食补充剂(HDS)的使用在美国呈指数增长。不幸的是,hds相关肝损伤的发生率呈比例增加。尽管某些hds可能导致临床上显著的肝损伤,但它们不受食品和药物管理局的监管。最近已经做出了一些努力来规范hds,但与处方药的审查相去甚远。关于hds及其引起肝损伤的风险的文献很少。在这篇全面的综述中,我们研究了HDS在美国的使用趋势以及某些HDS的药物性肝损伤(DILI)的病理生理机制。最后,我们回顾使用率;福利(如有);DILI的病理生理机制;与临床显著DILI相关的9例hds进展为暴发性肝衰竭的倾向。
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引用次数: 3
Inflammaging, a Common Factor in the Development of Sarcopenia and Metabolic-Associated Liver Disease (MAFLD) 炎症,一种发展为肌肉萎缩和代谢相关肝病(MAFLD)的常见因素
Pub Date : 2022-08-01 DOI: 10.3390/livers2030010
Gonzalo Jorquera, F. Cubero
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, with its prevalence increasing annually [...]
非酒精性脂肪肝(NAFLD)是西方国家最常见的肝病,其患病率每年都在增加〔…〕
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引用次数: 1
Seroprevalence of Hepatitis E Virus Antibodies (IgG) in the Community of Rawalpindi 拉瓦尔品第社区戊型肝炎病毒抗体(IgG)的血清流行率
Pub Date : 2022-07-27 DOI: 10.3390/livers2030009
Muhammad-Awais Farooqi, A. Ahsan, S. Yousuf, Noman Shakoor, H. Farooqi
Knowledge regarding the prevalence of the hepatitis E virus (HEV) in the general population can indicate public health and personal hygiene practices in a community. HEV spreads through the fecal-oral route and contaminates drinking water through sewage. Moreover, poverty also contributes to its prevalence in developing countries, including Pakistan. A cross-sectional study was conducted on 650 blood samples taken from suspected patients of HEV in the Rawalpindi cantonment area (Pakistan) from April to November 2019 at the Department of Virology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. Out of them, 444 (68.15%) were male and 206 (31.85%) were female; the detection of anti-HEV IgG antibodies was carried out using a commercial Anti-Hepatitis E virus antibody (IgG) ELISA Kit. The overall anti-HEV IgG prevalence percentages were 19.23% and 4.77% in males and females, respectively. Patients were categorized into eight groups with ages ranging between 1 and 90 years. HEV IgG seroprevalence was the highest in ages 31–40 (6.46%). The study concluded that males aged 40 or above were susceptible and infected with hepatitis E.
了解戊型肝炎病毒(HEV)在普通人群中的流行情况可以表明社区的公共卫生和个人卫生习惯。戊肝病毒通过粪口途径传播,并通过污水污染饮用水。此外,贫穷也助长了其在包括巴基斯坦在内的发展中国家的流行。对2019年4月至11月在巴基斯坦拉瓦尔品第武装部队病理研究所(AFIP)病毒学部从拉瓦尔品第营地地区(巴基斯坦)采集的650份HEV疑似患者血液样本进行了横断面研究。其中,男性444例(68.15%),女性206例(31.85%);采用市售戊型肝炎病毒抗体(IgG) ELISA试剂盒检测戊型肝炎病毒IgG抗体。男性和女性抗hev IgG总患病率分别为19.23%和4.77%。患者分为8组,年龄从1岁到90岁不等。31 ~ 40岁人群HEV IgG血清阳性率最高(6.46%)。研究得出结论,40岁或以上的男性易感染戊型肝炎。
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引用次数: 5
A Call for Implementation of an Evidence-Based, Quality Improvement, Decompensated Cirrhosis Discharge Care Bundle in Australia 呼吁在澳大利亚实施循证、质量改进、失代偿性肝硬化出院护理包
Pub Date : 2022-06-20 DOI: 10.3390/livers2020007
E. Kalo, N. Sheriff, Marina Isaac, A. Baig, S. Read, G. Ahlenstiel
A growing body of research suggests that evidence-based interventions can tackle high rates of hospital readmissions among patients with decompensated cirrhosis. Care bundles are a prime example of an evidence-based intervention to reduce hospital readmissions through documentation and communication. In this pilot study, a comprehensive baseline audit of electronic medical records of 497 discharges for 175 patients was conducted to assess the current standards of care on discharge from Blacktown Hospital, Australia, and the scope for introducing a care bundle. Our results demonstrated suboptimal discharge communication in a number of areas: Only 54% of decompensated cirrhosis patients had a follow-up appointment pre-scheduled at discharge. Despite alcohol being identified as a key cause of cirrhosis in 60% of patients, a review by alcohol services was conducted on only 24.9% of patients. Moreover, a general lack of focus on patient education and health literacy was identified. In conclusion, our pilot study has highlighted areas for improvement in the standard of care provided to this cohort of patients. Implementation of a standardized care bundle could address the current shortfalls, improve the standard of care and refocus discharge planning to address health literacy and education in patients admitted with a decompensated liver.
越来越多的研究表明,循证干预可以解决失代偿期肝硬化患者的高住院率问题。捆绑护理是循证干预的一个主要例子,通过文件和沟通减少医院再次入院。在这项试点研究中,对175名患者497次出院的电子医疗记录进行了全面的基线审计,以评估澳大利亚布莱克敦医院出院时的现行护理标准,以及引入一揽子护理的范围。我们的研究结果表明,在许多领域,出院沟通并不理想:只有54%的失代偿期肝硬化患者在出院时提前安排了随访预约。尽管酒精被确定为60%患者肝硬化的主要原因,但酒精服务机构仅对24.9%的患者进行了审查。此外,还发现普遍缺乏对患者教育和健康知识的重视。总之,我们的试点研究强调了为这群患者提供的护理标准需要改进的领域。实施标准化的一揽子护理可以解决目前的不足,提高护理标准,并重新关注出院计划,以解决肝脏失代偿患者的健康知识和教育问题。
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引用次数: 1
A Comprehensive Review on the Risk of Metabolic Syndrome and Cardiovascular Disease after Liver Transplantation 肝移植术后代谢综合征和心血管疾病风险的综述
Pub Date : 2022-04-29 DOI: 10.3390/livers2020006
Kashyap Chauhan, Adnan Khan, Salil Chowdhury, H. M. Ross, N. Parra, D. Halegoua-DeMarzio
Survival rates after liver transplantation have increased dramatically over the past 20 years. Cardiovascular disease is the most common extra-hepatic cause of mortality in the long-term post liver transplant. This is intimately linked with both the higher pre-existing rates of metabolic syndrome in these patients as well as increased propensity to develop de novo metabolic syndrome post-transplant. This unfavorable metabolic profile that contributes to cardiovascular disease is multifactorial and largely preventable. This review explores metabolic syndrome and cardiovascular disease and their contributory factors post liver transplantation to highlight areas for potential intervention and thus reduce the significant morbidity and mortality of patients due to metabolic syndrome and cardiovascular disease.
在过去的20年里,肝移植术后的存活率显著提高。心血管疾病是肝移植术后长期死亡最常见的肝外原因。这与这些患者较高的代谢综合征发生率以及移植后发生新发代谢综合征的倾向密切相关。这种导致心血管疾病的不利代谢特征是多因素的,在很大程度上是可以预防的。本文综述了肝移植后代谢综合征和心血管疾病及其影响因素,以突出潜在干预领域,从而降低代谢综合征和心血管疾病患者的显著发病率和死亡率。
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引用次数: 4
Anti-Inflammatory Dietary Approach to Prevent the Development and Progression of Non-Alcoholic Fatty Liver Diseases 抗炎饮食预防非酒精性脂肪肝的发展和进展
Pub Date : 2022-03-02 DOI: 10.3390/livers2010005
Dorothea Portius
Non-alcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide and is associated with insulin resistance, increased visceral fat mass, and cardiovascular problems. Lifestyle factors such as sedentary lifestyle, chronic stress, obesogenic environment as well as a Western pattern diet are main contributors to the development and progression of this disease. In particular, the diet plays a pivotal role. An unhealthy diet including high consumption of red and processed meats, refined carbohydrates, simple sugars, highly processed foods with food additives and conservatives are lighting the fire for a low-grade inflammation. If other risk factors come into play, metabolic and hormonal derangement may occur, leading to the increase in visceral fat, gut dysbiosis and leaky gut, which stoke the inflammatory fire. Thus, lifestyle interventions are the most effective approach to quell the inflammatory processes. An anti-inflammatory and low-glycemic diet named the GLykLich diet, which includes whole and unprocessed foods, may reduce the risk of increased morbidity and mortality. The GLykLich diet suggests a meal consisting of complex carbohydrates (fiber), good quality of protein and healthy fats (DHA/EPA), and is rich in secondary plant products. There is no single nutrient to prevent the progression of NAFLD, rather, it is the complexity of substances in whole unprocessed foods that reduce the inflammatory process, improve metabolic state, and thus reverse NAFLD.
非酒精性脂肪肝(NAFLD)是世界范围内日益严重的健康问题,与胰岛素抵抗、内脏脂肪量增加和心血管问题有关。久坐的生活方式、慢性压力、肥胖环境以及西方饮食等生活方式因素是导致这种疾病发展和进展的主要因素。特别是,饮食起着关键作用。一种不健康的饮食,包括大量食用红肉和加工肉、精制碳水化合物、单糖、含有食品添加剂的高度加工食品和保守派,正在为轻度炎症点燃火种。如果其他风险因素起作用,可能会发生代谢和激素紊乱,导致内脏脂肪增加、肠道生态失调和肠道渗漏,从而引发炎症。因此,生活方式干预是平息炎症过程的最有效方法。一种名为GLykLich饮食的抗炎低血糖饮食,包括完整和未加工的食物,可以降低发病率和死亡率增加的风险。GLykLich饮食建议膳食由复合碳水化合物(纤维)、优质蛋白质和健康脂肪(DHA/EPA)组成,并富含次生植物产品。没有单一的营养素可以阻止NAFLD的发展,相反,是整个未加工食品中物质的复杂性减少了炎症过程,改善了代谢状态,从而逆转了NAFLD。
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引用次数: 1
Acknowledgment to Reviewers of Livers in 2021 向2021年的肝脏评论家致谢
Pub Date : 2022-02-07 DOI: 10.3390/livers2010004
Rigorous peer-reviews are the basis of high-quality academic publishing [...]
严格的同行评议是高质量学术出版的基础[…]
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引用次数: 0
Oxidative Stress in Non-Alcoholic Fatty Liver Disease 非酒精性脂肪肝的氧化应激
Pub Date : 2022-02-01 DOI: 10.3390/livers2010003
C. Smirne, E. Croce, D. Di Benedetto, V. Cantaluppi, C. Comi, P. Sainaghi, R. Minisini, E. Grossini, M. Pirisi
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.
非酒精性脂肪性肝病(NAFLD)是一种由多种因素引起的具有挑战性的疾病,这可能部分解释了为什么它仍然是一个缺乏适当治疗的孤儿。本文综述了氧化应激(OS)与脂质代谢紊乱之间的相互作用。几种活性氧发生器,包括胃肠道中产生的活性氧发生器,在“多重平行撞击模型”中导致脂肪酸及其多种生物活性代谢物对肝脏(和肝外)造成脂毒性损伤。这会导致炎症和纤维化,并促进NAFLD的进展。氧化/抗氧化平衡的改变也会影响代谢相关的细胞器,导致脂质过氧化、线粒体功能障碍和内质网应激。这种os引起的损伤至少部分被生理抗氧化反应所抵消。因此,调节这一防御系统成为预防NAFLD发展和进展的一个有趣的靶点。例如,益生菌、益生元、饮食和粪便微生物群移植是针对肠道微生物群失调的新治疗方法。OS及其反调控也受到个体遗传和表观遗传因素的影响。在不久的将来,考虑到遗传或环境表观遗传风险因素的精准医学,加上新的OS生物标志物,可能有助于非侵入性诊断和监测NAFLD的进展以及进一步的个性化治疗。
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引用次数: 59
Cellular and Molecular Mechanisms Underlying Scope and Limitation of Ongoing and Innovative Therapies for Treating Chronic Hepatitis B 慢性乙型肝炎持续治疗和创新治疗的范围和局限性的细胞和分子机制
Pub Date : 2022-01-06 DOI: 10.3390/livers2010001
S. M. Akbar, Mamun Al Mahtab, O. Yoshida, Y. Hiasa
Millions of people of the world suffer from chronic hepatitis B (CHB), a pathological entity in which the patients are chronically infected with hepatitis B virus (HBV) and express hepatitis B surface antigen (HBsAg) and HBV DNA, as well as evidence of liver damages. Considerable numbers of CHB patients develop cirrhosis of the liver and hepatocellular carcinoma if untreated. Two groups of drugs (interferons and nucleoside analogs) are used to treat CHB patients, but both are endowed with considerable adverse effects, increased costs, extended duration of therapy, and limited efficacy. Thus, there is a pressing need to develop new and innovative therapeutics for CHB patients, and many such drugs have been developed during the last four decades. Some of these drugs have inspired considerable optimism to be a game-changer for the treatment of CHB. Here, we first discuss why ongoing therapeutics such as interferon and nucleoside analogs could not stand the test of time. Next, we dissect the scope and limitation of evolving therapies for CHB by dissecting the cellular and molecular mechanisms of some of these innovative therapeutics.
世界上有数百万人患有慢性乙型肝炎(CHB),这是一种病理实体,患者慢性感染乙型肝炎病毒(HBV)并表达乙型肝炎表面抗原(HBsAg)和HBV DNA,以及肝脏损伤的证据。如果不治疗,相当数量的慢性乙型肝炎患者会发展为肝硬化和肝细胞癌。两组药物(干扰素和核苷类似物)用于治疗慢性乙型肝炎患者,但两者都具有相当大的不良反应,费用增加,治疗时间延长,疗效有限。因此,迫切需要为慢性乙型肝炎患者开发新的和创新的治疗方法,在过去的四十年中已经开发了许多这样的药物。其中一些药物已经激发了相当大的乐观情绪,有望成为慢性乙型肝炎治疗的游戏规则改变者。在这里,我们首先讨论为什么正在进行的治疗,如干扰素和核苷类似物不能经受时间的考验。接下来,我们通过剖析一些创新疗法的细胞和分子机制来剖析CHB治疗方法的范围和局限性。
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引用次数: 0
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