血清Ⅲ型前胶原和透明质酸联合检测对慢性肝病的诊断价值

目的:研究血清Ⅲ型前胶原(PCⅢ)和透明质酸(HA)联合检测的临床诊断价值。方法:采用放射免疫分析法测定166例慢性肝病患者血清PCⅢ和HA。结果:PCⅢ值在慢活肝组(242.9±57.6μg/L)和肝硬化组(242.4±86.4μg/L)显著升高(P<0.01),但该两组间几无差异。HA在正常人(78.5±40.5μg/L)、慢迁肝(126.6±51.3μg/L)、慢活肝(274.2±120.3μg/L)、肝硬化(451.7±132.3μg/L)4组间依次呈递增趋势(P<0.05)。按Child-Pugh分级法,PCⅢ和HA在肝硬化A、B和C3级间依次呈递增趋势(P<0.05)。PCⅢ值与血清白蛋白水平呈负相关,与球蛋白水平呈正相关,HA与血清ALT、总胆红素呈正相关。结论:本研究结果说明PCⅢ与HA联合检测能同时反映肝纤维化的严重性、活动性和肝细胞的变性坏死。     

丁二磺酸腺苷蛋氨酸联合复方甘草酸苷治疗酒精性肝硬化患者疗效及其对血清BGP水平的影响

目的探讨应用丁二磺酸腺苷蛋氨酸肠溶片联合复方甘草酸苷治疗酒精性肝硬化患者的疗效及其对血清骨钙素(BGP)水平的影响。方法 2016年3月～2018年2月我院诊治的酒精性肝硬化患者276例,采用随机数字表法分为观察组(n=138)和对照组(n=138)。给予对照组患者丁二磺酸腺苷蛋氨酸肠溶片口服,观察组患者在对照组治疗的基础上给予复方甘草酸苷注射液静脉滴注,治疗3 w。采用放射免疫法检测血清BGP水平,采用ELISA法检测血清胰岛素样生长因子1(IGF-1)水平,采用化学发光免疫法检测血清透明质酸(HA)、黏连蛋白(LN)、Ⅳ型胶原(IV-C)和Ⅲ型前胶原(PC-Ⅲ)水平。结果在治疗结束时,观察组血清ALB为(36.8±10.3) g/L,显著高于对照组[(29.4±9.2) g/L,P0.05],血清TBIL为(26.4±5.1)μmol/L,显著低于对照组[(47.3±9.4)μmol/L,P0.05],血清GGT水平为(158.6±72.8) U/L,显著低于对照组[(254.6±100.4) U/L,P0.05];观察组血清HA为(72.6±18.4)μg/L,显著低于对照组[(158.4±30.5)μg/L,P0.05],LN为(87.4±8.3)μg/L,显著低于对照组[(165.3±19.8)μg/L,P0.05],PC-Ⅲ为(94.5±31.3)μg/L,显著低于对照组[(147.4±42.5)μg/L,P0.05],IV-C为(64.3±9.5)μg/L,显著低于对照组[(98.4±26.4)μg/L,P0.05];观察组血清IGF-1水平为(198.2±34.6)ng/ml,显著高于对照组[(162.5±30.5) ng/ml,P0.05],BGP为(8.8±3.9) ng/ml,显著高于对照组[(6.7±3.0) ng/ml,P0.05]。结论应用丁二磺酸腺苷蛋氨酸肠溶片联合复方甘草酸苷治疗酒精性肝硬化患者近期疗效显著,可显著改善患者肝功能指标,可能与升高了血清IGF-1和BGP水平有关。     

血清转化生长因子β1水平在慢性乙型肝炎与乙型肝炎肝硬化患者中差异的意义

目的:观察血清转化生长因子β1(TGFβ1)水平是否与肝脏炎症、纤维化程度相关及其在慢性乙型肝炎与乙肝肝硬化患者中的差异.方法:慢性乙肝(慢性肝炎组)65例,乙肝肝硬化(肝硬化组)56例,体检健康、乙肝标志物阴性者(正常对照组)50例,均空腹采血,肝纤维化指标(HA、CⅣ、PCⅢ、LN)采用放免法测定,血清TGFβ1检测采用ELISA.结果:慢性肝炎组血清TGFβ1水平明显高于肝硬化组和正常对照组(22±13μg/L vs 10±9μg/L,11±9μg/L,P<0.01),肝硬化组血清TGFβ1水平与正常对照组相比无显著性差异(P>0.05).肝硬化组PCⅢ与血清TGFβ1水平相关(r=0.269,P=0.045),慢性肝炎和肝硬化组血清TGFβ1水平与肝功能、肝纤维化指标无明显相关性(P>0.05).结论:血清TGFβ1水平可协助诊断肝脏炎症程度与纤维化程度,但不能作为他们的判断标准.     

血清透明质酸、Ⅲ型前胶原氨基端肽及层黏蛋白与老年慢性心力衰竭心肌纤维化相关性研究

目的 分析老年慢性心力衰竭(CHF)患者血清透明质酸(HA)Ⅲ型前胶原肽(PCⅢP)及层黏连蛋白(LN)与CHF及其心肌纤维化的关系.方法 采用放射免疫平衡法检测老年CHF组患者39例(心功能Ⅱ级14例,Ⅲ级21例,Ⅳ级4例,纽约心脏病学会分级法NYHA)及老年心功能Ⅰ级组(NYHA)46例血清HA,PCⅢP及LN浓度.结果 血清HA,PCⅢP及LN浓度分别为CHF组(359.75±84.59),(77.88±24.67),(86.73±23.90)μg/L;心功能Ⅰ级组(211.60±54.80),(64.82±23.99),(82.26±23.98)μg/L.与心功能Ⅰ级组比较,CHF组HA浓度显著增加(P＜0.05);两组间PCⅢP及LN浓度差异不显著(P＞0.05).结论 血清HA浓度升高可提示老年CHF及其心肌纤维化.     

Budd-Chiari综合征患者血清糖类抗原125水平与肝纤维化程度的相关性

目的:研究Budd-Chiari综合征(BCS)患者血清糖类抗原125(CA125)水平与肝纤维化程度的相关性。方法:选取2010年1月至2015年6月初次确诊的122例BCS患者作为研究组,依据Child-Pugh分级分A级组、B级组、C级组3个亚组,随机选取30例健康志愿者作为对照组,采用化学发光法测定血清CA125、层粘连蛋白(LN)、血清透明质酸(HA)、IV型胶原(IV-C)和Ⅲ型前胶原(PCⅢ)的水平。结果:(1)4组受试者血清CA125、LN、HA、IV-C、PCⅢ的水平比较差异均有统计学意义(P 0. 01),除了LN,其余指标水平均有随着肝硬化程度加重而升高的趋势;(2)BCS患者CA125阳性率在Child-Pugh A级组、B级组、C级组三组间比较差异具有统计学意义(P 0. 01),且与Child-Pugh分级呈正相关(P 0. 01);(3)BCS患者血清CA125水平与血清HA、IV-C、PCⅢ水平呈正相关(r=0. 232,0. 461,0. 345,P 0. 05),与LN水平没有相关性(P 0. 05)。结论:BCS患者血清CA125水平随着肝纤维化程度的加重而升高,有助于判断BCS患者的肝纤维化程度及预后。     

慢性乙型肝炎和肝硬化患者血清骨桥蛋白和TGF-β1水平变化

目的分析慢性乙型肝炎和肝硬化患者血清骨桥蛋白(OPN)和转化生长因子β1(TGF-β1)水平变化。方法选择慢性乙型肝炎患者268例,其中轻度54例、中度89例、重度73例和乙型肝炎肝硬化52例,采用ELISA法检测血清OPN和TGF-β1,采用化学发光免疫法检测血清III型前胶原(PC III)、IV型胶原(C IV)、层连蛋白(LN)和透明质酸(HA)。结果慢性乙型肝炎中度患者血清OPN和TGF-β1水平分别为(67.45±8.33)ng/ml和(164.30±34.61)pg/ml,显著高于慢性乙型肝炎轻度患者【分别为(31.28±7.45)ng/ml和(89.21±18.54)pg/ml,P0.05】;重度患者血清OPN和TGF-β1水平分别为(83.21±12.45)ng/ml和(248.95±52.33)pg/ml,显著高于轻度【分别为(31.28±7.45)ng/ml和(89.21±18.54)pg/ml,P0.05】或中度【分别为(67.45±8.33)ng/ml和(164.30±34.61)pg/ml,P0.05】;重度患者血清PC III和LN水平分别为(22.04±6.12)ng/ml和(181.06±37.89)ng/ml,显著高于轻度【分别为(13.84±3.11)ng/ml和(121.32±20.84)ng/ml,P0.05】;乙型肝炎肝硬化患者血清OPN和TGF-β1水平分别为(138.42±29.11)ng/ml和(456.39±97.60)pg/ml,显著高于慢性乙型肝炎患者(P0.05);无论是在肝炎还是肝硬化患者,血清OPN水平与血清PC III、C IV、LN、HA水平呈显著正相关(r=0.397、r=0.416、r=0.402、r=0.435,P0.05);血清TGF-β1水平与PC III、C IV、LN、HA水平呈显著正相关(r=0.426、r=0.493、r=0.415、r=0.481,P0.05)。结论慢性乙型肝炎和肝硬化患者血清OPN和TGF-β1水平升高,可能与肝纤维化发生有关。     

婴儿肝炎综合征患儿血清肝纤维化指标及与肝功能相关性研究

目的分析婴儿肝炎综合征患儿血清肝纤维化指标及其与肝功能相关性,为疾病评估提供参考。方法选取我院在2010年2月—201 5年5月收治婴儿肝炎综合征患儿62例为研究对象,根据超声诊断结果分为观察组33例和对照组29例,分析肝纤维化指标水平,并分析与肝功能相关性。结果观察组ALT(278±213)U/L、DBil(163±82)μmol/L、IBil(81±35)μmol/L以及TBil(241±106)μmol/L等显著高于对照组ALT(1 57±106)U/L、DBil(106±57)μmol/L、IBil(50±26)μmol/L以及TBil(1 56±94)μmol/L,P).05,观察组CHE指标(4475±1237)U/L显著低于对照组(5627±1 526)U/L,P0.05,观察组HA、IV-C显著高于对照组HA235±206)ng/mL、IV-C(267±126)ng/mL,P0.05,HA与ALT、GGT呈现正相关,PC-Ⅲ与TBA、GGT呈现正相关,IV-C与ALT、TBil等呈现正相关,LN未发现相关性指标,HA和IV-C指标与肝功能相关性最高。结论婴儿肝炎综合征血清肝纤维化指标与肝功能存在明显相关性,联合检测对评估患者病情有重要价值。     

肝脏瞬时弹性成像技术及血清肝纤维化指标在肝硬化中的评估作用

目的探讨肝脏瞬时弹性成像技术及血清肝纤维化指标在肝硬化中的评估价值。方法研究对象为青海省人民医院2017年9月～2018年3月收治的125例病毒性肝炎肝硬化患者,根据肝硬化Child-Pugh分级分为A级67例,B级32例,C级26例,另选取30例健康体检者作为对照组。检测所有研究对象的血清肝纤维化4项指标[透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)],并对所有肝硬化患者进行肝脏瞬时弹性成像检查。比较不同肝硬化Child-Pugh分级患者的肝纤维化4项指标及肝脏硬度值(LSM)。结果肝硬化Child-Pugh分级A、B、C级组患者血清HA、LN、PCⅢ、Ⅳ-C水平均显著高于对照组(P0.05),且肝纤维化4项指标血清水平随着肝硬化Child-Pugh分级的增加而明显升高,各组间比较差异均有统计学意义(P0.05)。肝硬化Child-Pugh分级A级患者LSM显著低于肝硬化Child-Pugh分级B级与C级,肝硬化Child-Pugh分级B级患者LSM又显著低于肝硬化Child-Pugh分级C级,三组比较有显著差异(P0.05)。通过对血清肝纤维化指标、LSM与Child-Pugh分级总分的Pearson相关分析得出,血清HA、LN、PCⅢ、Ⅳ-C、LSM水平与Child-Pugh分级总分呈正相关(P0.05)。结论肝硬化患者的肝硬化Child-Pugh分级越高,肝纤维化4项指标血清水平越高,LSM越大,肝脏瞬时弹性成像技术及血清肝纤维化指标可作为肝硬化严重程度评估的有效手段。     

聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者临床疗效研究

目的探讨应用聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者的临床疗效。方法 2003年1月～2016年12月我院就诊的代偿期丙型肝炎肝硬化患者122例,采用随机数字表法分成两组,每组61例。给予对照组常规护肝治疗,给予观察组聚乙二醇化干扰素α-2a联合利巴韦林治疗24～48 w。随访两组24 w。采用实时荧光定量RT-PCR法检测血清HCV RNA,采用全自动生化分析仪检测血生化指标,采用化学发光法检测血清层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA),常规使用Fibroscan行肝脏硬度检测(LSM)。结果在治疗结束时,观察组血清HCV RNA水平为(2.0±0.4) lg IU/ml,显著低于对照组【(3.8±1.3)lg IU/ml,P0.05】;血清AST和ALT水平分别(46.03±24.05) U/L和(36.32±20.1) U/L,显著低于对照组【(78.7±21.1)U/L和(51.2±20.9) U/L,P0.05);观察组血清LN、PCⅢ和HA水平分别为(126.3±29.0)μg/L、(212.3±43.8)μg/L和(211.4±42.0)μg/L,均显著低于对照组【(140.3±32.1)μg/L、(267.5±39.8)μg/L和(329.6±68.4)μg/L,P0.05】;观察组LSM为(13.6±2.4) kPa,显著低于对照组【(17.6±5.2)kPa,P0.05】;在随访时发现,观察组血清ALT复常率和持续病毒学应答率(SVR)均显著高于对照组(分别为93.4%对45.9%和72.1%对9.8%,P0.05),而疾病进展发生率为3.3%,显著低于对照组的13.1%(P0.05)。结论应用聚乙二醇化干扰素α-2a联合利巴韦林抗病毒治疗代偿期丙型肝炎肝硬化患者可显著提高SVR,延缓肝纤维化进展,稳定肝功能指标。     

劳拉西泮与奥沙西泮治疗酒精性肝病并发酒精戒断综合征患者临床疗效对比研究

目的 对比观察劳拉西泮与奥沙西泮治疗酒精性肝病(ALD)并发酒精戒断综合征(AWS)患者的临床疗效。方法 2017年11月～2020年11月我院诊治的127例ALD并发AWS患者,采用随机数字表法将患者分为对照组63例和观察组64例,分别给予劳拉西泮和奥沙西泮治疗7 d。应用酒精戒断综合征评定量表(AWSS)评估临床症状,应用焦虑自评量表(SAS)评估焦虑症状。采用ELISA法检测血清透明质酸(HA)、层粘连蛋白(LN)、三型前胶原N端肽(PC-Ⅲ)和四型胶原(IV-C)。结果 在治疗结束时,观察组有效率为96.9％,显著高于对照组的81.0％,差异有统计学意义(P<0.05);治疗前,两组AWSS和SAS评分和血清ALT、AST、GGT、TBIL、ALP、CHE、HA、LN、PC-Ⅲ和IV-C水平无统计学差异(P>0.05);治疗结束时,观察组AWSS和SAS评分分别为(9.5±2.4)分和(30.8±6.4)分,与对照组【分别为(14.2±3.5)分和(48.2±9.1)分,P<0.05】比,差异显著;血清ALT、AST、GGT、TBIL和ALP水平分别为(30.5±8.1)U/L、(71.6±15.3)U/L、(466.1±22.7)U/L、(23.5±6.5)μmol/L和(82.3±12.4)U/L,显著低于对照组【分别为(52.2±11.3)U/L、(105.6±18.4)U/L、(626.3±25.4)U/L、(35.2±8.6)μmol/L和(118.3±14.7)U/L,P<0.05】;血清HA、PC-Ⅲ和IV-C水平分别为(116.8±18.3)μg/L、(123.1±12.3)μg /L和(80.2±11.6)μg /L,显著低于对照组【分别为(146.2±22.3)μg/L、(155.5±16.8)μg/L和(98.8±15.4)μg/L,P<0.05】。结论 奥沙西泮治疗ALD并发AWS患者临床疗效显著,可改善症状,减轻焦虑情绪,促进肝功能恢复。     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

Recurrent nonviral liver disease following liver transplantation

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence. It is important to recognize that rates of recurrence vary according to indication and show little correlation with rates of graft loss from recurrent disease. Recurrance rates are greatest for primary sclerosing cholangitis and autoimmune hepatitis, and low reccurrance rates are reported for alcoholic liver disease and recurrent primary biliary cirrhosis. The impact of recurrent nonalcoholic fatty liver disease is not yet clear. Patients and clinicians need to be aware of the possibility of recurrent disease in the differential diagnosis of abnormal liver tests, and management stategies may require alteration to reduce the impact of disease recurrence on outcome. Finally, an understanding of which diseases do recur after transplantation and identification of the risk factors may lead to a better understanding of the pathogenetic mechanisms of these conditions.     

中国肝癌肝移植的现状与展望

肝癌行肝移植治疗的指征、效果和相关问题一直存在争论,国际上已经有数个通用的肝癌肝移植标准,如Milan标准、Pittsburgh标准、UCSF标准等等,中国的移植学家们也在纷纷探讨适合中国的肝癌肝移植标准.本文收集并分析近年来国内外的文献,结合本移植中心460例肝移植的病例,对肝癌的分期标准、晚期肝癌行肝移植的指征进行了探讨,笔者认为影响我国肝癌肝移植的主要因素有:供肝的来源、术后乙肝及肿瘤的复发及相关社会因素等.     

Chronic liver diseases as liver tumor precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.     

Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.     

Orthotopic liver transplantation for alcoholic liver disease

Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.     

Adult liver transplantation for metabolic liver disease

Liver replacement provides an effective method of replacing a failing liver, and corrects the underlying defect in many metabolic conditions. Results of liver transplantation for metabolic diseases have been encouraging, with the exception of hereditary hemochromatosis, in which infectious and for which cardiac complications appear to increase posttransplant mortality. An improved understanding of the underlying genetic and molecular defect will lead to advances in medical therapy and perhaps will decrease the need for liver replacement. The prospects of gene therapy are being pursued for many metabolic disorders, however until this research leads to direct clinical application, liver transplantation remains the only effective option for many patients with metabolic liver disease.