肝源性糖尿病45例临床分析

目的探讨肝源性糖尿病的临床特点及治疗。方法观察45例肝硬化合并肝源性糖尿病患者的临床表现,检测治疗前、治疗后的血糖情况并进行比较分析。结果肝源性糖尿病患者以肝病表现为主,血糖波动较大,以餐后2h血糖升高为主;而Child-pugh分级C级患者的血糖明显高于A、B级患者,有并发症的患者血糖明显高于无并发症的患者。结论肝硬化患者易发生糖代谢紊乱,血糖水平与肝功能情况密切相关,经早期积极治疗,血糖基本可降至理想范围并稳定。     

不同病因肝硬化患者临床特征及其预后影响因素分析

摘要 目的：探讨不同病因肝硬化患者临床特征及其预后影响因素。方法：回顾性选择2017年1月至2020年12月来我院诊治的具有完整资料，同时明确诊断为肝硬化，病因为乙肝后肝硬化（78例）、酒精性肝硬化（42例）。分析两组患者的一般资料、并发症发生情况、合并疾病情况，分析乙肝后肝硬化、酒精性肝硬化患者的预后影响因素。结果：两组患者在性别、职业、临床表现（黄疸、黑便、呕血、蜘蛛痣、脾脏增大）、肝脏体积缩小、并发症（上消化道出血、肝性脑病）、合并疾病（脂肪肝、糖尿病、胰腺炎、胆结石）方面有统计学意义（P<0.05）。乙肝后肝硬化组的疾病进展发生率明显较酒精性肝硬化组高（P<0.05）。单因素分析结果表明，临床表现（乏力、食欲减退、皮肤瘙痒、腹痛、腹胀、呕血、黑便、腹水）、Child-Pugh分级、并发症（上消化道出血、肝性脑病）是影响乙肝后肝硬化患者预后的因素（P<0.05）；Logistic回归分析结果表明，Child-Pugh分级在B、C级、存在上消化道出血与肝性脑病是影响乙肝后肝硬化患者预后的危险因素（P<0.05）。单因素分析结果表明，临床表现（黄疸）、Child-Pugh分级、并发症（上消化道出血、肝性脑病、感染）是影响酒精性肝硬化患者预后的因素（P<0.05）；Logistic回归分析结果表明，Child-Pugh分级为C级、存在上消化道出血肝性脑病、感染是影响酒精性肝硬化患者预后的危险因素（P<0.05）。结论：乙肝后肝硬化与酒精性肝硬化的差异主要体现在性别、职业、临床表现、并发症与合并疾病中，影响乙肝后肝硬化预后的危险因素为Child-Pugh分级在B、C级、存在上消化道出血与肝性脑病，影响酒精性肝硬化预后的危险因素为Child-Pugh分级为C级、存在上消化道出血、肝性脑病、感染，需防治并发症，以改善患者预后。     

Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system

The administration of branched-chain amino acids (BCAAs) to cirrhosis patients increases serum albumin levels and improves the blood Fischer's ratio. Although it has been reported that albumin synthesis in rat primary hepatocytes is diminished under lower Fisher's ratio conditions compared to normal Fischer's ratio conditions, the mode of action at the molecular level for these effects is still uncertain. It has been reported recently that the triggering signal for protein synthesis is transmitted through mTOR (mammalian target of rapamycin). We have had an interest in the mTOR signal transduction system. In the present study, we analyzed the mode of action of BCAA-induced albumin synthesis using rat primary hepatocytes. The BCAA mixture dose-dependently promoted the production of albumin, with leucine being the major effector half of which was inhibited by the mTOR inhibitor rapamycin. We also showed that only leucine induces P70 S6 kinase activation and 4E-BP1 phosphorylation which are mTOR's downstream translational effectors. These activations were completely inhibited by rapamycin. Our results suggest that BCAAs, especially leucine, promote the production of albumin in rat primary hepatocytes through an mTOR signal transduction system.     

丽珠肠乐（回春生）对肝硬化的疗效观察

丽珠肠乐（回春生）为双歧杆菌活菌制剂,给７３例肝硬化失代期病人口服２２～６７天。治疗前后分别检测血内毒素含量及肝功能,观察其疗效。结果表明本制剂对肝硬化的疗效明显,总有效率为７９．４５％,其中内毒素水平治疗后明显下降,与治疗前比较,Ｐ＜０．０１,有效率为８７．６７％。肝功能各指标有不同程度的改善,有效率７８．０８％。说明回春生是当代最新的微生态调节剂。     

Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional difference gel electrophoresis and mass spectrometry

Proteome analysis of human hepatocellular carcinoma tissues was conducted using two-dimensional difference gel electrophoresis coupled with mass spectrometry. Paired samples from the normal and tumor region of resected human liver were labeled with Cy3 and Cy5, respectively while the pooled standard sample was labeled with Cy2. After analysis by the DeCyder software, protein spots that exhibited at least a two-fold difference in intensity were excised for in-gel tryptic digestion and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A total of 6 and 42 proteins were successfully identified from the well- and poorly-differentiated samples, respectively. The majority of these proteins are related to detoxification/oxidative stress and metabolism. Three down-regulated metabolic enzymes, methionine adenosyltransferase, glycine N-methyltransferase, and betaine-homocysteine S-methyltransferase that are involved in the methylation cycle in the liver are of special interest. Their expression levels, especially, methionine adenosyltransferase, seemed to have a major influence on the level of S-adenosylmethionine (AdoMet), a vital intermediate metabolite required for the proper functioning of the liver. Recent work has shown that chronic deficiency in AdoMet in the liver results in spontaneous development of steatohepatitis and hepatocellular carcinoma, and hence the down-regulation of hepatic methionine adenosyltransferase in our hepatocellular carcinoma samples is in line with this observation. Moreover, when a comparison is made between the differentially expressed proteins from our human hepatocellular carcinoma samples and from the liver tissues of knockout mice deficient in methionine adenosyltransferase, there is a fairly good correlation between them.     

Specific gene expression patterns in liver cirrhosis

Liver cirrhosis (LC) is a complex disease that can develop into hepatocellular carcinoma (HCC). In an effort to investigate genetic differences between LC and HCC, we used cDNA microarray analysis to characterize the gene expression profiles in LC and HCC tissues. Consistent differences were observed among the expression patterns in LC, HCC, and normal liver tissues. Interestingly, the expression patterns of LC without tumor association (LCT) were also readily distinguished from those of LC tissues near hepatic tumor tissues (near-tumor tissue, NTT). Moreover, 25 cirrhosis-specific genes could be used to divide the NTT samples into two groups: inflammatory active cirrhosis (NTTa) and inflammatory inactive cirrhosis (NTTi). We found that NTTa samples showed gene expression patterns similar to those of the LCT and HCC groups, whereas the expression patterns of the NTTi group were significantly different from those of the LCT, NTTa, and HCC groups. Finally, we selected two of the 25 LC-specific genes and showed that these markers could be used to successfully discriminate among the different LC subtypes. Collectively, these novel results allow the identification of new genetic subgroups of LC and provide new candidate genes for use as early markers for active cirrhosis and HCC.     

Protective effects of Rosmarinus tomentosus ethanol extract on thioacetamide-induced liver cirrhosis in rats

The capability of an ethanol extract of Rosmarinus tomentosus to protect rat liver in an experimental model of cirrhosis induced by thioacetamide (TAA) has been evaluated. Four groups of rats were used: Two of them received 300 mg TAA/l in the drinking water for 3 months while the other two, which served as controls, were given water ad libitum. During the same period and for each one of the treatments, one group received a semi-purified (SP) diet and the other one was fed the same diet supplemented with 1% of the dry residue obtained from R. tomentosus ethanol extract (SP+E). There was a significant reduction of TAA toxicity in rats fed the SP+E diet, as assessed by plasma and liver biochemical markers, and by liver histopathology. Plasma total protein concentration was restored, urea concentration and plasma alkaline phosphatase and gamma-glutamyl-transferase activities were reduced. A significant correction of plasma fatty acids concentrations was also evident. Hepatic alkaline phosphatase and gamma-glutamyl-transferase activities were significantly reduced in animals fed SP+E diet and glucose-6-phosphatase activity was significantly enhanced. The results suggest that R. tomentosus ethanol extract administered in the diet affords protection against TAA-induced cirrhosis, preventing most of the histological changes and functionality alterations own to this experimental pathology.     

病毒性肝病抗病毒治疗期间新发肝癌7例临床分析

目的:探讨病毒性肝炎肝硬化患者经抗病毒治疗仍发生原发性肝癌的原因。方法:回顾性分析兰州大学第一医院东岗院区肝病中心在2012年10月-2013年6月收治的7例病毒性肝炎肝硬化患者在规范抗病毒治疗期间新发原发性肝癌的临床资料、抗病毒治疗情况。结果:7例患者中有HBV感染6例,HCV感染1例;慢性肝炎2例,肝硬化5例;HBeAg阴性5例;3例合并糖尿病;经抗病毒治疗后病毒载量均处于低度复制或不可测状态。结论:病毒性肝炎肝硬化患者经抗病毒治疗不能完全消除原发性肝癌发生的风险,病毒载量、HBeAg阴性、糖尿病、肝硬化等可能是肝癌发生的危险因素。     

ALK1-Smad1/5 signaling pathway in fibrosis development: Friend or foe?

Fibrosis is a common phenomenon associated with several pathologies, characterized by an excessive extracellular matrix deposition that leads to a progressive organ dysfunction. Thus fibrosis has a relevant role in chronic diseases affecting the kidney, the liver, lung, skin (scleroderma) and joints (arthritis), among others. The pathogenesis of fibrosis in different organs share numerous similarities, being one of them the presence of activated fibroblasts, denominated myofibroblast, which act as the main source of extracellular matrix proteins. Transforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine that plays a pivotal role in fibrosis. The TGF-β1/ALK5/Smad3 signaling pathway has been studied in fibrosis extensively. However, an increasing number of studies involving the ALK1/Smad1 pathway in the fibrotic process exist. In this review we offer a perspective of the function of ALK1/Smad1 pathway in renal fibrosis, liver fibrosis, scleroderma and osteoarthritis, suggesting this pathway as a powerful therapeutical target. We also propose several strategies to modulate the activity of this pathway and its consequences in the fibrotic process.     

肠道菌群失调与肝硬化伴SBP患者疾病发展的关系及三联活菌胶囊干预性研究

目的分析肠道菌群失调与肝硬化伴自发性细菌性腹膜炎(SBP)患者疾病发展的关系及三联活菌胶囊的应用价值。方法将我院2017年1月至2019年12月间收治的94例肝硬化伴SBP患者作为观察组研究对象,50例健康者作为本研究对照组,将观察组患者依照随机信封法分为B组及A组,B组采用三联活菌胶囊治疗,A组采用常规方案治疗。采用16S rDNA测序技术检测患者肠道菌群种类和多样性。结果观察组患者诺卡氏菌科、盐单胞菌科、肠杆菌科、链球菌科、韦荣球菌科丰度均高于对照组,拟杆菌科、普雷沃菌科、毛螺菌科均低于对照组,OTUs、Chao、Shannon指数明显低于对照组。肠道菌群种类、OTUs、Chao、Shannon指数是影响肝硬化伴SBP患者疾病发展的影响因素,以上差异均就有统计学意义(P0.05)。治疗后B组患者肠道菌群OTUs、Chao和Shannon明显高于对照组,差异均具有统计学意义(P0.05)。结论肠道菌群失调是影响肝硬化伴SBP患者疾病发展的独立影响因素,采用三联活菌胶囊干预可有效纠正患者体内肠道菌群失调。