慢性肝病与成体肝干细胞

慢性肝病中,肝细胞作为单能干细胞参与肝脏修复,还存在类似于动物致癌、损伤模型中卵圆细胞的肝干细胞或肝前体细胞,这些细胞均能活化并分化成肝细胞和胆管上皮,与临床慢性肝病的发生发展密切相关,主要包括胆管反应中的卵圆细胞和小肝细胞,定位于Hering管、汇管区、纤维间隔、汇管区旁肝实质、假小叶及炎症边界,根据超微结构特点分为三型,可以表达一系列标记物,还可能是骨髓、胰腺来源。     

HBV所致终末期肝病患者肝组织胆管增生的研究

目的在乙型肝炎病毒（HBV）所致的终末期肝病患者肝组织内，常可见大量的胆管增生，但其发生机制及临床意义尚不清楚。为阐明该类患者胆管增生的发生机制及其与卵圆细胞增生及肝细胞再生的关系，我们对8例HBV相关的终末期肝病患者及2例正常人肝组织进行了免疫组化染色及图像分析。方法肝组织连续切片后进行免疫组化染色，观察指标为细胞角蛋白CK7、CK8、CK18、CK19、OV6、增殖细胞核抗原（PCNA）、谷胱甘肽S转移酶（GSTπ）、白蛋白（ALB）及甲胎蛋白（AFP）。结果在所有8例患者肝组织汇管区内均可见典型增生的胆管及非典型增生的胆管，且对CK7、CK8、CK9、CK19、OV6及PCNA染色呈阳性反应，但两种类型的胆管在染色强度上存在明显差异。一些非典型增生的胆管细胞表现出肝卵圆细胞的形态学及免疫组化特征。某些小型肝细胞样细胞在形态及免疫组化特征方面介于肝卵圆细胞及成熟肝细胞之间。结论在HBV相关的终末期肝病患者肝组织内，胆管增生可能存在不同起源。某些非典型增生的胆管细胞实际上就是活化的肝卵圆细胞。非典型增生的胆管细胞与肝细胞再生密切相关。小型肝细胞样细胞可能是肝卵圆细胞与成熟肝细胞之问的中间过渡细胞。     

肝脏自然杀伤细胞在慢性肝病中的作用

肝脏自然杀伤细胞（NK）是一种与外周血NK细胞不同的肝脏免疫细胞。近年来研究表明肝脏NK细胞在各种慢性肝脏疾病中起重要作用。包括对抑制病毒感染和肿瘤细胞生长,对抗肝纤维化均有益处,但同时其又刺激肝损伤和抑制肝再生（肝细胞增殖）。本文就肝脏NK细胞的特征、功能以及在各种常见慢性肝病中作用进展作一综述。     

内皮型一氧化氮合酶在慢性乙型肝炎肝组织中的表达

目的研究内皮型一氧化氮合酶(endothelium-type nitric oxide synthase,eNOS)在慢性乙型肝炎肝组织中的表达及其与病理改变的关系。方法应用免疫组化法观察了41例慢性乙型肝炎患者肝组织中eNOS的变化。结果 eNOS见于肝细胞,窦内皮细胞,枯否细胞,血管内皮细胞,单个核细胞,及增生的卵圆细胞,呈胞浆型,细颗粒型,粗颗粒型及胞膜型分布,以肝细胞为主,在炎症病变活动区相对集中。并发现其表达随肝组织病变活动程度增加而增强,与炎症程度的相关系数为0.5327(P<0.05),与纤维化程度无明显相关性。结论 eNOS与慢性乙肝肝组织病理改变密切相关。     

慢性肝病患者血清中的游离脯氨酸与游离羟脯氨酸

胶原的特征之一是脯氨酸和羟脯氨酸的含量较高。羟脯氨酸几为哺乳动物的胶原所特有,它在血清及尿中的水平可反映在胶原代谢转换较高的组织中胶原的代谢程度。在某些胶原合成活跃的病理情况下,游离脯氨酸池也有所改变。如在肝硬化患者的肝脏,游离脯氨酸池的增加与肝纤维化的程度是成比例的。本文的目的在于确定酒精性肝硬化患者血清中游离脯氨酸及羟脯氮酸的水平能否反映肝内纤维组织的代谢状态。对71例肝病患者及62例对照者的血清游离脯氨酸及游离羟脯氨酸进行了测定。肝病组包括60例肝硬化和11例慢性活动性肝病患者。肝硬化患者中有     

慢性肝病患者血清IL-6变化的意义

早期发现、阻断和逆转肝纤维化是治疗慢性肝病的关键.目前肝纤维化的发病机制仍不十分明确.细胞因子在肝纤维化形成中的作用已受到重视[1].为此,我们对88例慢性乙型病毒性肝炎和肝炎肝硬变患者同时检测了血清IL-6活性、血清Ⅲ型前胶原蛋白(PCⅢ)、层粘连蛋白(LN)、透明质酸酶(HA)含量,并与其中27例肝组织学结果进行对照研究,以探讨IL-6在慢性肝病肝纤维化形成中的意义.     

非肝病及慢性乙型肝炎患者肝组织中巨细胞病毒的检测

目的：探讨巨细胞病毒（CMV）在非肝病患者及慢性乙型肝炎患者肝组织中的表达、分布特点及相关关系。方法：采用免疫组化方法以抗－CMV单克隆抗体对31例非肝病及76例慢性乙型肝炎肝组织进行检测，用抗－HBcAg多克隆抗体和抗－CMV单克隆抗体双标记技术在部分慢性乙型肝炎患者同一张肝组织切片上显示两种病毒分布特点。结果：31例非肝病肝组织中检出CMV Ag7例（22．6％），明显低于慢性乙型肝炎患者（43／76，56．6％），P＜0．01。在两组标本中CMV Ag均在肝细胞胞浆内表达。非肝病患者肝组织中阳性细胞数量较慢性乙型肝炎患者少，后者阳性细胞多近汇管区分布，数量多时，也可在肝小叶内弥漫分布。轻度和重度慢性乙型肝炎患者中CMV的检出率比较，差异无显著性，但慢性乙肝炎患者中CMV表达阳性细胞明显多于轻度慢性乙型肝炎（P＜0．05）。双标记染色显蒜CMV Ag和HBcAg多数可表达于肝小叶内同一区域肝细胞甚至同一肝细胞内，也可见于肝小叶中不同部位。结论：非肝病患者中CMV感染并不少见，慢性乙肝炎患者更易重叠CMV感染，并且其感染程度与肝组织的活动性病变密切相关。     

肝脏弹性与慢性肝病患者的营养状况的关系研究

目的明确肝脏弹性值与慢性肝病患者营养状况的相关性。方法采用瞬时弹性成像(Fibro Scan)评价205例慢性肝病患者的肝纤维化情况,根据Fibro Scan值将患者分为4个不同肝纤维化组别,应用营养风险筛查表(NRS 2002)对各组患者进行营养风险筛查,主观综合性营养评估(SGA)评价其营养不良状况,使用Spearman秩相关方法分析其相关性。结果应用NRS 2002筛查4组处于不同肝纤维阶段患者的营养风险,结果提示伴随肝纤维化程度逐渐加重,营养风险发生率增加,营养不良状况恶化,患者的握力下降,肱三头肌皮褶厚度及上臂围减少,化验白蛋白及前白蛋白、淋巴细胞计数均逐渐降低,差异均有统计学意义(P0.05)。存在营养风险的慢性肝病患者较无营养风险组的肝脏弹性值增高,肝硬化组符合这一特点,而肝炎组的不同营养风险患者的肝脏弹性值差异无统计学意义(P=0.4762)。结论不同肝脏弹性的慢性肝病患者其营养状况存在差异,营养风险以及营养不良与肝脏弹性值有关。     

瞬时弹性成像技术与APRI指数判定慢性肝病肝纤维化程度的临床研究

目的评估肝脏瞬时弹性成像技术(Fibro Scan,FS)的应用价值,为肝纤维化的准确诊断提供安全、可靠的检测方法。方法选择2014年3月至2015年5月就诊于漯河市中心医院和郑州大学第一附属医院并经肝组织活检确定为慢性肝病患者168例,运用FS检测肝脏硬度(LSM);测定丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL);检测血小板计数,并计算AST/PLT比值(APRI)。以肝活组织检查病理结果为依据,分析LSM、APRI与肝纤维化程度的相关性。应用SPSS 17.1统计软件进行统计分析。绘制受试者工作特征曲线分析二者诊断慢性肝病肝纤维化的准确性,Spearman相关分析影响肝硬度值的相关因素。结果 168例慢性肝病患者LSM值中位数为10.8 k Pa;APRI中位数为0.71;LSM值与肝纤维化成正相关(r=0.832,P=0.000),LSM诊断肝组织病理学纤维化分期S≥2,S≥3及S=4的ROC曲线下面积分别为0.894,0.923和0.951,明显高于APRI(0.691,0.715及0.736)诊断的ROC曲线下面积。Spearman相关分析显示,LSM与年龄、ALT≥2倍正常上限值、AST、TBIL及肝组织炎症呈正相关,相关系数r分别为0.486、0.570、0.617、0.481及0.549(P0.05),与PLT呈负相关(r=-0.527,P0.05)。结论FS是一种简便、可靠的慢性肝病肝纤维化诊断方法,其灵敏度及特异度均优于APRI。年龄、高水平的ALT、AST和TBIL≥2×ULN是其独立的影响因素。     

FibroTouch联合肝纤维化四项生化指标评估慢性血吸虫病肝病患者肝纤维化程度价值

目的 评价联合使用FibroTouch技术及肝纤维化四项生化指标检测对慢性血吸虫病肝病患者肝纤维化程度的效果.方法 以2021年1-3月昆山市第三人民医院收治的63例慢性血吸虫病肝病患者作为观察组,另选择同期在该院进行健康体检的50例健康志愿者作为对照组.用FibroTouch技术检测两组研究对象肝脏硬度值(LSM),...     

重视慢性肝病的病情评估

<正>肝病患者的病情评估对于制定及时、有效的临床治疗策略具有重要意义。慢性肝病的病情评估涉及肝纤维化及肝硬化、活动性的肝细胞坏死及炎症、肝硬化并发症及预后等多个方面。1肝纤维化及肝硬化的评估肝穿刺活检是判断肝纤维化程度最直接、最准确的方法,尤其对非酒精性脂肪性肝炎(NASH)的确诊、病毒性肝炎患者抗病毒药物治疗时机选择、     

Sarcopenia and chronic liver diseases

ABSTRACT

Introduction: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with various chronic diseases, including chronic liver diseases. Growing lines of evidence indicate that sarcopenia not only correlates with the clinical outcomes and survival of patients undergoing liver transplant, but also serves as a prognostic factor for candidates of liver transplantation and patients with hepatocellular carcinoma.

Areas covered: In this review, we conducted a narrative review and search of literature from PubMed, Ovid MEDLINE, and the Cochrane Library database up to August 2018. Studies relevant to the emerging data of sarcopenia and chronic liver diseases were examined and discussed.

Expert commentary: Although sarcopenia has been shown to play a vital role in the outcomes of cirrhotic patients with or without liver transplant, its impact on non-cirrhotic patients remains unclear and deserves future research efforts. To develop an effective and practical measurement of sarcopenia has become an urgent issue in the management of patients with chronic liver diseases.

Abbreviations: HCC: hepatocellular carcinoma; L3SMI: third lumbar vertebra skeletal muscle index; NAFLD: nonalcoholic fatty liver disease; VAT: visceral adipose tissue; PMA: psoas muscle area; LT: liver transplantation; AUC: area under the curve; LC: liver cirrhosis; SPPB: short physical performance battery; HU: Hounsfield units; ASM: appendicular skeletal muscle; SMI: skeletal muscle index; FLI: fatty liver index; PCLD: polycystic liver disease; DEXA: dual energy X-ray absorptiometry; BCAAs: branched-chain amino acids; BIA: bioelectrical impedance analysis; CT: computed tomography; OS: overall survival; CSA: cross-sectional area; NASH: nonalcoholic steatohepatitis; TPMT: transversal psoas muscle thickness; IMAC: intramuscular adipose tissue content; LDLT: living donor liver transplantation; PMI: psoas muscle mass index; PMTH: psoas muscle thickness by height; TPA: total psoas area; OLT: orthotopic liver transplantation; 6MWD: Six-minute walk distance; HRQOL: health-related quality of life; SMA: skeletal muscle area     

炎症小体与慢性肝脏疾病

多种慢性肝脏疾病都与组织的无菌性炎症有关。核苷酸结合寡聚化结构域样受体家族形成的多蛋白复合物——炎症小体,作为炎症反应的核心,能被多种外源或内源性刺激激活,引起下游炎症因子分泌,诱发炎症反应,其过度激活会造成组织损伤。现已证实炎症小体在酒精性和非酒精性脂肪性肝病、肝脏缺血再灌注损伤及药物性肝损伤等疾病中起关键作用,是肝脏发生纤维化和癌变的决定因素之一。本文就炎症小体的结构、活化信号及激活通路、调节机制及其与慢性肝脏疾病关系的研究进展作一综述,以期为慢性肝脏疾病的治疗提供新的方向和靶点。     

肝脏疾病细胞铁死亡研究进展

目的 铁死亡是一种新发现的细胞死亡方式,是由于细胞内铁离子水平异常升高,导致氧化还原失衡,细胞膜发生脂质过氧化,最终细胞膜破裂,导致细胞死亡。目前认为铁死亡的中心环节是铁代谢和活性氧代谢。铁死亡可以影响多种疾病的发生发展过程,例如神经退行性疾病、肿瘤、缺血再灌注损伤、免疫性疾病等。越来越多的研究表明,在多种肝脏疾病的发生发展过程中均出现不同程度的铁超载和脂质活性氧堆积等铁死亡特征。铁死亡可以通过调节细胞内铁离子水平和脂质过氧化程度影响肝脏疾病的进程。本文将针对肝脏疾病发病过程中细胞铁死亡研究进展进行综述。     

Kidneys in chronic liver diseases

Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support.     

Osteodystrophy in chronic liver diseases

Osteoporosis and osteomalacia are, to date, among the most common metabolic diseases in the world. Lately, an association between metabolic bone diseases and chronic liver disease has been increasingly reported, inducing many authors to create a new nosographic entity known as ‘hepatic osteodystrophy.’ The importance of such a condition is further increased by the morbidity of these two diseases, which greatly reduce the quality of life because of frequent fractures, especially vertebral and femoral neck ones. For this reason, early identification of high-risk patients should be routinely performed by measuring bone mass density. The explanation for the association between bone diseases and chronic liver disease is still uncertain, and involves many factors: from hypogonadism to use of corticosteroid drugs, from genetic factors to interferon therapy. To date, few studies have been conducted, and all with a small number of patients to establish definitive conclusions about the possible treatment, but some evidence is beginning to emerge about the safety and efficacy of bisphosphonates.     

Molecular genetics of chronic liver diseases

The molecular genetics of five common single gene and one polygenic chronic liver disease is discussed. In two of the single gene disorders, alpha 1-antitrypsin deficiency and cystic fibrosis, the gene responsible is now known and the repertoire of different mutations underlying the disease is being defined. In the other three single gene defects (haemochromatosis, polycystic liver disease and Wilson's disease) the chromosomal location of the disease allele is known. It is anticipated that recombinant DNA techniques will enable the genes responsible for these diseases to be cloned in the near future, thus allowing the biochemical abnormalities to be defined through reverse genetics. In many chronic liver diseases the relative contribution of genetic and environmental factors remains unclear. Evidence suggests there is a definite genetic component in predisposition to alcoholic cirrhosis; the role of putative candidate genes is discussed. It is hoped that the definition of a genetic locus linked to alcoholic cirrhosis will ultimately teach us more about the basic pathogenesis of this disease.