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1.
Background and aimsThe LISTEN trial (ClinicalTrial.gov accession: NCT01950884) is a phase IV 52 weeks double blind parallel randomized controlled trial that evaluated the effect of ezetimibe plus lifestyle and dietary intervention (eze) vs. lifestyle and dietary intervention alone (placebo) on progression and complications of non-alcoholic steatohepatitis (NASH) evaluated by liver histology.Methods and resultsForty patients with NASH ascertained by histology were randomly allocated on the two study groups and subjected to a follow-up of 52 weeks, when they underwent a second liver biopsy. Main composite end point (EP) was based on the histological improvement in the severity of NASH.Thirty patients completed the study, Eze treatment was not able to improve the primary EP in comparison with placebo, with and odds ratio of 1.029 (0.18–6.38), p = 0.974. Treatment emergent adverse events registered during the study were not more prevalent in the treatment arm.Conclusionsezetimibe administered on top of lifestyle and dietary modification failed to improve the histology of NASH in comparison with lifestyle and dietary modification alone.Trial accession numberClinicalTrial.gov: NCT01950884.  相似文献   
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IntroductionIdiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials.MethodsSpanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed.Results225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6 min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern.ConclusionsPatients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.  相似文献   
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目的 探讨慢性乙型肝炎(CHB)患者肝X受体α(LXRα)和细胞色素P450亚型7A1(CYP7A1)基因表达水平与肝组织病理学炎症和纤维化程度的关系。方法 2019年1月~2020年10月我院收治的CHB患者118例,均接受肝穿刺活检,将炎症活动度分级>G2和肝纤维化分期>S2定义为肝组织炎症或纤维化程度显著;采用免疫组织化学染色法检测肝组织LXRα和CYP7A1表达,采用RT-PCR法检测LXRα mRNA和CYP7A1 mRNA水平。结果 118例CHB患者肝组织LXRα和CYP7A1蛋白和/或其mRNA阳性分别为78.0%和73.7%;38例肝组织显著炎症组LXRα mRNA和其蛋白(AOD)水平分别为(0.6±0.2)和(0.3±0.1),显著高于80例非显著炎症患者[分别为(0.4±0.1)和(0.1±0.0),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.8±0.2)和(0.4±0.1),显著高于非显著炎症患者[分别为(0.3±0.1)和(0.1±0.0),P<0.05];48例显著肝纤维化组肝组织LXRα mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于70例非显著肝纤维化患者[分别为(0.3±0.1)和(0.1±0.1),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于非显著肝纤维化患者[分别为(0.4±0.2)和(0.2±0.1),P<0.05]。结论 LXRα和CYP7A1表达上调可能参与了CHB患者肝组织炎症和肝纤维化发生发展过程,其机制值得进一步研究。  相似文献   
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Background and study aimsPregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients.Patients and methodsWe prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8–12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed.ResultsOur cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01–6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32–7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827.ConclusionLS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.  相似文献   
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目的 分析节律分子Timeless(TIM)相互作用蛋白(TIM interacting protein,TIPIN)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其与患者预后的关系,并探究TIPIN对肝癌细胞增殖的影响及可能的生物学作用机制。方法 通过UALCAN数据库分析TIPIN在HCC组织中的表达情况及其与HCC患者预后的关系。将siTIPIN及其阴性对照序列分别转染至肝癌MHCC⁃97H细胞,采用qRT⁃PCR和Western blot检测TIPIN的表达情况,采用MTS实验和平板细胞克隆形成实验检测TIPIN表达对细胞增殖的影响。利用UALCAN数据库对TIPIN进行GO和KEGG富集分析,以及TIPIN与TIM、TP53的关联分析。 结果 UALCAN数据库分析结果显示,TIPIN在HCC组织中的表达明显高于正常肝组织(P<0.01);TIPIN高表达患者的总生存期和无病生存期均明显短于TIPIN低表达患者(P=0.037,0.021)。与正常肝细胞HL7702相比,肝癌细胞MHCC⁃97H、MHCC⁃97L、HepG2、BEL⁃7402中TIPIN的mRNA和蛋白表达水平均明显升高(均P<0.01)。MTS和克隆形成实验结果显示,沉默TIPIN表达后肝癌MHCC⁃97H细胞的增殖和平板细胞克隆形成能力明显受到抑制(均P<0.05)。GO和KEGG富集分析结果显示,TIPIN可能通过调控细胞分裂、DNA复制、细胞周期的相互作用通路促进肝癌的恶性进程。Pearson相关性分析结果显示,TIPIN分子与TIM表达呈明显正相关(r=0.67,P<0.01)。TIPIN在TP53突变HCC患者中的表达显著高于TP53野生型HCC患者(P<0.01)。 结论 TIPIN在肝癌中表达上调,且与患者不良预后密切相关,沉默TIPIN可抑制肝癌细胞增殖。TIPIN在肝癌中可能通过与TIM形成复合体或调控TP53信号通路发挥其生物学作用。  相似文献   
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目的 对中国人群肝癌发病危险因素的病例对照研究进行综合定量分析,为肝癌的防控和卫生决策提供理论依据。方法 系统地检索Pubmed、中国知网、万方数据库、中国医院知识仓库发表的中国人群肝癌影响因素的病例对照研究,检索自数据库建立到2021年5月1日的所有中英文文献。用纽卡斯尔-渥太华量表评价文献质量,用R 4.0.2软件进行meta分析。结果 共检索文献1799篇,根据纳入与排除标准筛选,最终有53篇病例-对照研究纳入系统评价。meta分析结果显示,肝癌的危险因素按照其关联性由强到弱依次为:HBV感染、肝病史、精神因素、HCV感染、癌症家族史、糖尿病、食用霉变食物、饮酒、吸烟、饮用不洁水源,合并 OR值最高为9.79(95%CI:7.93~11.65),最低为1.32(95%CI:1.08~1.56)。饮茶为保护因素,合并OR值为0.28(95%CI:0.17~0.39)。敏感性分析、发表偏倚检验与剪补法分析结果显示,本研究纳入的文献整体上敏感性低,发表偏倚控制较好。结论 病毒感染、肝病史、饮酒等不健康生活方式为我国人群肝癌发病的危险因素,饮茶为保护因素。建议积极接种乙肝疫苗,改变不良饮食习惯和生活方式,加强肝癌的早预防、早发现、早诊断、早治疗。  相似文献   
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Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.  相似文献   
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