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Outcome of bariatric surgery in patients with unexpected liver cirrhosis: A multicenter study from China 意外肝硬化患者的减肥手术效果:中国多中心研究
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.08.001
Xia Sun , Libin Yao , Xing Kang , Weihua Yu , Fidele Kakule Kitaghenda , Mohammad Sajjad Ibn Rashid , Angeline Nogue Taguemkam , Jian Hong , Zhiyong Dong , Xitai Sun , Xiaocheng Zhu

Background and aims

Liver cirrhosis is a complex disease that may result in increased morbidity and mortality following bariatric surgery (BS). This study aimed to explore the outcome of BS in patients with unexpected cirrhosis, focusing on postoperative complications and the progression of liver disease.

Methods

A retrospective study of bariatric patients with cirrhosis from four centers in China between 2016 and 2023 was conducted, with follow-up for one year after BS. The primary outcome was the safety of BS in patients with unexpected cirrhosis, while the secondary outcome was the metabolic efficacy of BS in this group postoperatively.

Results

A total of 47 patients met the study criteria, including 46 cases of Child-Pugh class A cirrhosis and 1 case of Child-Pugh B. Pathological examination confirmed nodular cirrhosis in 21 patients (44.68%), pseudolobule formation in 1 patient (2.13%), lipedema degeneration with inflammatory cell infiltration in 3 patients (6.38%), and chronic hepatitis in 1 patient (2.13%). The average percentage of total weight loss was 29.73 ± 6.53% at one year postoperatively. During the 30-day postoperative period, the complication rate was 6.38%, which included portal vein thrombosis, gastrointestinal bleeding, and intra-abdominal infection. Moreover, no cases of liver decompensation or mortality were reported during the follow-up period. The remission rates of comorbidities among 41 patients one year after surgery were as follows: dyslipidemia 100%, type 2 diabetes 82.61%, hypertension 84.62%, and obstructive sleep apnea syndrome 85.71%.

Conclusions

BS can be safely performed in patients with unexpected cirrhosis in the compensated stage of liver disease, with low postoperative morbidity and no mortality observed during one-year follow-up.
背景和目的肝硬化是一种复杂的疾病,可能导致减肥手术(BS)后发病率和死亡率增加。本研究旨在探讨意外肝硬化患者接受减重手术的结果,重点关注术后并发症和肝病进展。方法对中国四个中心在 2016 年至 2023 年期间接受减重手术的肝硬化患者进行回顾性研究,并在减重手术后随访一年。主要结果是意外肝硬化患者接受 BS 的安全性,次要结果是该组患者术后接受 BS 的代谢疗效。结果共有 47 例患者符合研究标准,包括 46 例 Child-Pugh A 级肝硬化和 1 例 Child-Pugh B 级肝硬化。病理检查证实结节性肝硬化 21 例(44.68%),假小叶形成 1 例(2.13%),脂肪水肿变性伴炎症细胞浸润 3 例(6.38%),慢性肝炎 1 例(2.13%)。术后一年,总重量的平均百分比为(29.73 ± 6.53)%。术后 30 天内,并发症发生率为 6.38%,包括门静脉血栓、消化道出血和腹腔内感染。此外,随访期间没有出现肝功能失代偿或死亡病例。41例患者术后一年的合并症缓解率如下:血脂异常100%、2型糖尿病82.61%、高血压84.62%、阻塞性睡眠呼吸暂停综合征85.71%。
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引用次数: 0
Inhaled nitric oxide as a salvage therapy for refractory hypoxemia in the post-transplantation period of hepatopulmonary syndrome: An explorative report of three cases 吸入一氧化氮作为肝肺综合征移植后难治性低氧血症的挽救疗法:三例病例的探索性报告
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.09.005
Haijin Lyu , Xiaomeng Yi , Yunshan Zou , Pinglan Lu , Lijuan Li , Jianrong Liu , Senbiao Chen , Xuxia Wei , Yang Yang , Huimin Yi
Liver transplantation (LT) is the only effective treatment for hepatopulmonary syndrome (HPS). Moreover, perioperative refractory hypoxemia (pRH) is a prevalent life-threatening condition and has extremely limited treatment options. Here, we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies, ephedrine inhalation, intravenous use of methylene blue with nitric oxide (NO) inhalation, and NO inhalation alone. The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury. Early initiation of NO inhalation, rather than ephedrine, can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications. Therefore, based on the response to these exploratory salvage treatments, we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS. We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.
肝移植(LT)是治疗肝肺综合征(HPS)的唯一有效方法。此外,围手术期难治性低氧血症(pRH)是一种普遍存在的危及生命的病症,其治疗方案极其有限。在此,我们报告了三名在 LT 术后出现 pRH 的 HPS 患者,他们分别接受了麻黄碱吸入、亚甲蓝静脉注射与一氧化氮(NO)吸入以及单用一氧化氮吸入等不同的挽救疗法。结果表明,未解决的严重缺氧可能会诱发致命的病症,如早期胆漏和急性肾损伤。早期开始吸入 NO 而不是麻黄素,可显著改善 pRH 患者的氧合状况,并有助于预防缺氧相关并发症。因此,根据对这些探索性抢救治疗的反应,我们进一步证明了 HPS 在 pRH 期间特定肺部区域独特的通气-灌注不匹配病理生理学。我们建议,在LT围手术期,早期吸入NO是挽救HPS患者严重缺氧的重要治疗选择。
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引用次数: 0
Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury 白细胞细胞衍生趋化因子 2 (LECT2) 调节肝脏缺血再灌注损伤
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.09.004
Meng-Qi Dong , Yuan Xie , Zhi-Liang Tang , Xue-Wen Zhao , Fu-Zhen Lin , Guang-Yu Zhang , Zhi-Hao Huang , Zhi-Min Liu , Yuan Lin , Feng-Yong Liu , Wei-Jie Zhou

Background and aim

Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors.

Materials and methods

This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.

Results

Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential.

Conclusions

Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.
背景和目的肝脏缺血再灌注损伤(IRI)是肝移植、创伤、低血容量休克和肝切除术中的一个重大挑战,目前有效的干预措施有限。本研究旨在探讨白细胞细胞衍生趋化因子2(LECT2)在肝脏IRI中的作用,并评估通过腺相关病毒(AAV)载体递送的Lect2-短发夹RNA(shRNA)的治疗潜力。研究使用了 Lect2- 基因剔除小鼠和 C57BL/6J 小鼠。通过夹闭肝梗诱导肝脏IRI。治疗包括重组人LECT2(rLECT2)和AAV-Lect2-shRNA。测量了LECT2的表达水平和血清生物标志物,包括丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肌酐和血尿素氮(BUN)。结果肝脏IRI期间血清和肝脏LECT2水平升高。再灌注后血清 LECT2 蛋白和 mRNA 水平升高。Lect2 基因敲除小鼠的体重减轻、肝坏死和血清 ALT、AST、肌酐和 BUN 水平降低。AAV-LECT2-shRNA治疗显著减轻了体重下降、肝坏死和血清生物标志物(谷丙转氨酶、谷草转氨酶、肌酐和尿素氮),显示出治疗潜力。基因敲除或 shRNA 介导的 Lect2 基因敲除可减轻肝损伤,显示了其治疗潜力。AAV介导的Lect2-shRNA递送减轻了肝脏IRI,为提高肝脏相关手术或外伤患者的临床疗效提供了一种潜在的新治疗策略。
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引用次数: 0
Meldonium-induced steatosis is associated with increased delta 6 desaturation and reduced elongation of n-6 polyunsaturated fatty acids 美敦力诱发的脂肪变性与δ6脱饱和度增加和n-6多不饱和脂肪酸伸长减少有关
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.09.001
Bodil Bjørndal , Siri Lunde Tungland , Pavol Bohov , Magne O. Sydnes , Simon N. Dankel , Lise Madsen , Rolf K Berge

Background and objective

Metabolic associated fatty liver disease (MAFLD) is associated with abnormal lipid metabolism. Mitochondrial dysfunction is considered an important factor in the onset of MAFLD, whereas altered fatty acid composition has been linked to the severity of the disease. Tetradecylthioacetic acid (TTA), shown to induce mitochondrial proliferation and alter the fatty acid composition, was used to delay the accumulation of hepatic triacylglycerol. This study aimed to evaluate how impaired mitochondrial fatty acid beta-oxidation affects fatty acid composition by incorporating meldonium into a high-carbohydrate diet.

Methods

C57BL/6 mice (n = 40) were fed high-carbohydrate diets supplemented with meldonium, TTA, or a combination of meldonium and TTA for 21 days. Lipid levels were determined in liver samples, and fatty acid composition was measured in both liver and plasma samples. Additionally, desaturase and elongase activities were estimated. The hepatic activities and gene expression levels of enzymes involved in fatty acid metabolism were measured in liver samples, whereas carnitines, their precursors, and acylcarnitines were measured in plasma samples.

Results

The meldonium-induced depletion of L-carnitine and mitochondrial fatty acid oxidation was confirmed by reduced plasma levels of L-carnitine and acylcarnitines. Principal component analyses of the hepatic fatty acid composition revealed clustering dependent on meldonium and TTA. The meldonium-induced increase in hepatic triacylglycerol levels correlated negatively with estimated activities of elongases and was associated with higher estimated activities of delta-6 desaturase (D6D; C18:4n-3/C18:3n-3 and C18:3n-6/C18:2n-6), and increased circulating levels of C18:4n-3 and C18:3n-6 (gamma-linolenic acid). TTA mitigated meldonium-induced triacylglycerol levels by 80% and attenuated the estimated D6D activities, and elongation of n-6 polyunsaturated fatty acids (PUFAs). TTA also attenuated the meldonium-mediated reduction of C24:1n-9 (nervonic acid), possibly by stimulating Elovl5 and increased elongation of erucic acid (C22:1n-9) to nervonic acid. The hepatic levels of nervonic acid and the estimated activity of n-6 PUFA elongation correlated negatively with the hepatic triacylglycerol levels, while the estimated activities of D6D correlated positively.

Conclusion

Circulating levels of gamma-linolenic acid, along with reduced estimated elongation of n-6 PUFAs and D6D desaturation activities, were associated with hepatic triacylglycerol levels.
背景和目的代谢相关性脂肪肝(MAFLD)与脂代谢异常有关。线粒体功能障碍被认为是导致代谢相关性脂肪肝发病的重要因素,而脂肪酸组成的改变则与疾病的严重程度有关。十四烷基硫代乙酸(TTA)可诱导线粒体增殖并改变脂肪酸组成,被用于延缓肝脏三酰甘油的积累。本研究旨在通过在高碳水化合物膳食中添加美多萘,评估线粒体脂肪酸β-氧化作用受损如何影响脂肪酸组成。测定肝脏样本中的脂质水平,并测定肝脏和血浆样本中的脂肪酸组成。此外,还估算了去饱和酶和伸长酶的活性。在肝脏样本中测量了参与脂肪酸代谢的酶的肝活性和基因表达水平,而在血浆样本中测量了肉碱、其前体和酰基肉碱。肝脏脂肪酸组成的主成分分析显示了依赖于美多鎓和 TTA 的聚类。麦角铵诱导的肝脏三酰甘油水平的增加与拉长酶的估计活性呈负相关,并与δ-6去饱和酶(D6D;C18:4n-3/C18:3n-3 和 C18:3n-6/C18:2n-6)的估计活性升高以及 C18:4n-3 和 C18:3n-6 (γ-亚麻酸)的循环水平升高有关。TTA 可使麦芽酮诱导的三酰甘油水平降低 80%,并降低估计的 D6D 活性和 n-6 多不饱和脂肪酸(PUFA)的伸长。TTA 还可能通过刺激 Elovl5 和增加芥酸(C22:1n-9)向神经酸的延伸,减弱了美多农介导的 C24:1n-9(神经酸)的减少。结论γ-亚麻酸的循环水平、n-6 PUFAs 的估计伸长率和 D6D 的估计脱饱和活性的降低与肝脏三酰甘油水平呈负相关。
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引用次数: 0
Genetic engineering drives the breakthrough of pig models in liver disease research 基因工程推动猪模型在肝病研究中实现突破
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.09.003
Chenhao Xu , Xixi Fang , Xiao Xu , Xuyong Wei
Compared with the widely used rodents, pigs are anatomically, physiologically, and genetically more similar to humans, making them high-quality models for the study of liver diseases. Here, we review the latest research progress on pigs as a model of human liver disease, including methods for establishing them and their advantages in studying cystic fibrosis liver disease, acute liver failure, liver regeneration, non-alcoholic fatty liver disease, liver tumors, and xenotransplantation. We also emphasize the importance of genetic engineering techniques, mainly the CRISPR/Cas9 system, which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease research. Genetic engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.
与广泛使用的啮齿类动物相比,猪在解剖学、生理学和遗传学上与人类更为相似,是研究肝脏疾病的优质模型。在此,我们回顾了猪作为人类肝病模型的最新研究进展,包括建立猪模型的方法及其在研究囊性纤维化肝病、急性肝衰竭、肝脏再生、非酒精性脂肪肝、肝脏肿瘤和异种移植方面的优势。我们还强调了基因工程技术的重要性,主要是CRISPR/Cas9系统,该系统大大提高了猪模型的实用性,成为大幅推动肝病研究的工具。基因工程有望推动猪成为未来生物医学研究中不可替代的动物模型之一。
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引用次数: 0
Resmetirom: Breakthrough therapeutic approach for metabolic dysfunction-associated steatohepatitis Resmetirom:代谢功能障碍相关性脂肪性肝炎的突破性治疗方法
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.07.002
Anzel Saeed, Kuldeep Dalpat Rai, Muzammil Saeed
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引用次数: 0
Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B 非肝硬化慢性乙型肝炎患者停用核苷酸类似物后的长期乙型肝炎表面抗原动力学研究
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.07.001
Lina Wu , Jiadi Lai , Qiumin Luo , Yeqiong Zhang , Chaoshuang Lin , Dongying Xie , Youming Chen , Hong Deng , Zhiliang Gao , Liang Peng , Wenxiong Xu

Background and aim

Few studies have reported hepatitis B surface antigen (HBsAg) kinetics after nucleos(t)ide analog (NA) discontinuation in patients with noncirrhotic chronic hepatitis B (CHB). The study specifically investigated long-term HBsAg kinetics after NA discontinuation.

Methods

Between January 2014 to January 2024, this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment. Demographic, clinical, and laboratory data were collected and analyzed after NA discontinuation.

Results

Ninety-six patients who finished 5 years of follow-up were included. HBsAg remained undetectable in 29 patients with end of treatment (EOT) HBsAg negativity. Among 67 patients with EOT HBsAg positivity, HBsAg seroclearance occurred in 12 (17.9%) patients with an estimated annual incidence of HBsAg seroclearance of 3.6%. Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of >1000 IU/mL (33.3% vs. 5.4%). The proportion of patients with HBsAg ≤1000 IU/mL increased during follow-up. Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL. The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL.

Conclusions

Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation. A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation. Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Clinical trial number

Clinicaltrials.gov number NCT02883647.
背景和目的很少有研究报道非肝硬化慢性乙型肝炎(CHB)患者停用核苷类似物(NA)后的乙肝表面抗原(HBsAg)动力学。该研究特别调查了停用 NA 后的长期 HBsAg 动力学。方法在 2014 年 1 月至 2024 年 1 月期间,该研究前瞻性地招募了 106 名门诊非肝硬化慢性乙型肝炎患者,这些患者在接受 NA 巩固治疗后符合停药标准。结果纳入了96名完成5年随访的患者。在治疗结束(EOT)HBsAg阴性的29名患者中,HBsAg仍然检测不到。在 67 名 EOT HBsAg 阳性患者中,有 12 人(17.9%)的 HBsAg 血清清除,估计每年 HBsAg 血清清除的发生率为 3.6%。EOT HBsAg 水平≤1000 IU/mL 的患者的 HBsAg 血清清除率高于 EOT HBsAg 水平>1000 IU/mL 的患者(33.3% 对 5.4%)。随访期间,HBsAg≤1000 IU/mL的患者比例有所增加。逻辑回归分析表明,EOT HBsAg水平是HBsAg血清清除和HBsAg水平下降超过1 log10 IU/mL的独立因素。结论EOT HBsAg阴性患者在NA停药后的5年随访期间没有复发,并保持HBsAg血清清除。在停用 NA 后的 5 年随访期间,EOT HBsAg 水平≤1000 IU/mL 的患者可获得更高的 HBsAg 血清清除率。临床试验编号Clinicaltrials.gov number NCT02883647。
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引用次数: 0
Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end? 肝细胞癌患者的门静脉肿瘤血栓形成:是终点吗?
Q2 Medicine Pub Date : 2024-09-01 DOI: 10.1016/j.livres.2024.09.002
Walaa Abdelhamed , Hend Shousha , Mohamed El-Kassas
Hepatocellular carcinoma (HCC) is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality. The incidence of portal vein tumor thrombosis (PVTT) in HCC patients is 21% at one year and 46% at three years. The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades. Notably, HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT. Currently, there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT. The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C, indicating an advanced stage, and limiting treatment recommendations for these patients to systemic therapy. In recent years, there has been an increase in the availability of therapeutic options for HCC patients with PVTT. Treatment modalities include systemic therapy, transarterial chemoembolization, surgical resection, stereotactic body radiotherapy, transarterial radioembolization, and liver transplantation. An ideal therapy for each patient necessitates a multidisciplinary approach. This review article presents the latest updates in managing HCC patients with PVTT.
肝细胞癌(HCC)是全球发病率第六高的癌症,也是导致癌症相关死亡的第三大原因。门静脉瘤栓形成(PVTT)在 HCC 患者中的发生率为一年 21%,三年 46%。过去几十年来,PVTT 的存在一直与 HCC 患者的不良预后相关。值得注意的是,HCC 的预后不仅受 PVTT 的存在影响,还受 PVTT 的程度或范围影响。目前,对于伴有 PVTT 的 HCC 的最佳治疗方法还缺乏全球共识或既定方案。巴塞罗那肝癌诊所将伴有 PVTT 的 HCC 患者分为 C 期,这表明患者已进入晚期,并建议这些患者仅限于接受全身治疗。近年来,针对伴有 PVTT 的 HCC 患者的治疗方案越来越多。治疗方式包括全身治疗、经动脉化疗栓塞、手术切除、立体定向体放射治疗、经动脉放射栓塞和肝移植。要为每位患者提供理想的治疗方案,必须采用多学科方法。这篇综述文章介绍了治疗患有 PVTT 的 HCC 患者的最新进展。
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引用次数: 0
Liver-specific glucocorticoid action in alcoholic liver disease: Study of glucocorticoid receptor knockout and knockin mice 肝脏特异性糖皮质激素在酒精性肝病中的作用:糖皮质激素受体基因敲除和基因敲入小鼠的研究
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.1016/j.livres.2024.06.001
Yazheng Wang, Conor Fahy, Hong Lu

Background and aim

Glucocorticoids are the only first-line drugs for severe alcoholic hepatitis (AH), with limited efficacy and various side effects on extrahepatic tissues. Liver-targeting glucocorticoid therapy may have multiple advantages over systemic glucocorticoid for AH. The aim of this study was to determine the role of hepatocellular glucocorticoid receptor (GR) in alcohol-associated steatosis (AS) and AH.

Materials and methods

AS was induced by a high-fat diet plus binge alcohol in adult male and female mice with liver-specific knockout (LKO) and heterozygote of GR. AH was induced by chronic-plus-binge in middle-aged male mice with liver-specific knockin of GR. Changes in hepatic mRNA and protein expression were determined by quantitative real-time polymerase chain reaction and Western blot.

Results

GR-LKO aggravated steatosis and decreased hepatic expression and circulating levels of albumin in both genders of AS mice but only increased markers of liver injury in male AS mice. Marked steatosis in GR-LKO mice was associated with induction of lipogenic genes and down-regulation of bile acid synthetic genes. Hepatic protein levels of GR, hepatocyte nuclear factor 4 alpha, and phosphorylated signal transducer and activator of transcription 3 were gene-dosage-dependently decreased, whereas that of lipogenic ATP citrate lyase was increased in male GR heterozygote and LKO mice. Interestingly, hepatic expression of estrogen receptor alpha (ERα) was induced, and the essential estrogen-inactivating enzyme sulfotransferase 1e1 was gene-dosage-dependently down-regulated in GR heterozygote and knockout AS mice, which was associated with induction of ERα-target genes. Liver-specific knockin of GR protected against liver injury and steatohepatitis in middle-aged AH mice.

Conclusions

Hepatic GR deficiency plays a crucial role in the pathogenesis of AS induced by high-fat diet plus binge, and liver-specific overexpression/activation of GR protects against chronic-plus-binge-induced AH in middle-aged mice. Hepatocellular GR is important for protection against AS and AH.

背景和目的糖皮质激素是治疗重症酒精性肝炎(AH)的唯一一线药物,但疗效有限,且对肝外组织有各种副作用。与全身使用糖皮质激素相比,肝脏靶向糖皮质激素治疗酒精性肝炎可能具有多种优势。本研究旨在确定肝细胞糖皮质激素受体(GR)在酒精相关性脂肪变性(AS)和AH中的作用。对肝脏特异性基因敲除(LKO)和杂合子的中年雄性小鼠,通过慢性加酗酒诱导AH。结果GR-LKO加重了AS小鼠的脂肪变性,降低了肝脏表达和白蛋白的循环水平,但只增加了雄性AS小鼠的肝损伤指标。GR-LKO小鼠明显的脂肪变性与脂肪生成基因的诱导和胆汁酸合成基因的下调有关。在雄性GR杂合子和LKO小鼠中,GR、肝细胞核因子4α和磷酸化信号转导和转录激活因子3的肝脏蛋白水平呈基因剂量依赖性下降,而致脂性ATP柠檬酸酶的水平则升高。有趣的是,雌激素受体α(ERα)的肝脏表达被诱导,而在GR杂合子小鼠和基因敲除AS小鼠中,必需的雌激素灭活酶磺基转移酶1e1的基因剂量依赖性下调,这与ERα靶基因的诱导有关。结论肝脏GR缺乏在高脂饮食加暴饮暴食诱导的AS发病机制中起关键作用,肝脏特异性过表达/激活GR可保护中年小鼠免受慢性加暴饮暴食诱导的AH。肝细胞GR对预防AS和AH具有重要作用。
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引用次数: 0
Hepatitis B virus as a risk factor for hepatocellular carcinoma: There is still much work to do 乙型肝炎病毒是肝细胞癌的危险因素:仍有许多工作要做
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.1016/j.livres.2024.05.004
Walaa Abdelhamed , Mohamed El-Kassas

Hepatitis B virus (HBV) infection is a significant health problem that can result in progression to liver cirrhosis, decompensation, and the development of hepatocellular carcinoma (HCC). On a country level, the prevalence of chronic HBV infection varies between 0.1% and 35.0%, depending on the locality and the population being investigated. One-third of all liver cancer fatalities worldwide are attributable to HBV. The adoption of standard birth-dose immunization exerted the most significant impact on the decline of HBV prevalence. HCC incidence ranges from 0.01% to 1.40% in noncirrhotic patients and from 0.9% to 5.4% annually, in the settings of liver cirrhosis. Although antiviral therapy significantly reduces the risk of developing HBV-related HCC, studies have demonstrated that the risk persists, and that HCC screening is still essential. This review discusses the complex relationship between HBV infection and HCC, recent epidemiological data, different aspects of clinical disease characteristics, and the impact of antiviral therapy in this context.

乙型肝炎病毒(HBV)感染是一个严重的健康问题,可导致肝硬化、肝功能失代偿和肝细胞癌(HCC)的发展。在全国范围内,慢性 HBV 感染率介于 0.1% 和 35.0% 之间,具体取决于所调查的地区和人群。全球三分之一的肝癌死亡病例可归因于 HBV。标准出生剂量免疫接种的采用对 HBV 感染率的下降产生了最显著的影响。非肝硬化患者的 HCC 发病率为 0.01% 至 1.40%,肝硬化患者的 HCC 年发病率为 0.9% 至 5.4%。尽管抗病毒治疗可大大降低罹患 HBV 相关 HCC 的风险,但研究表明这种风险依然存在,因此 HCC 筛查仍然至关重要。本综述讨论了 HBV 感染与 HCC 之间的复杂关系、最新流行病学数据、临床疾病特征的不同方面以及抗病毒治疗在这方面的影响。
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Liver Research
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