肝病伴糖代谢异常患者的临床分析

目的探讨肝病伴糖代谢异常的临床特点及其可能机制.方法分别对29例慢性乙型肝炎伴糖代谢异常患者及62例乙型肝炎后肝硬化伴糖代谢异常患者进行相关分析.结果 （1）乙型肝炎后肝硬化患者中肝源性糖耐量减低（IGT）及肝源性糖尿病（DM）发生率高于慢性乙型肝炎患者（20.53%对3.82%,P＜0.05;24.11%对1.64%,P＜0.01）.（2）慢性乙型肝炎及乙型肝炎后肝硬化伴肝源性IGT或DM患者均无糖尿病症状,而19例慢性乙型肝炎伴原发性DM者中12例有症状,12例乙型肝炎后肝硬化伴原发性DM者中6例有症状.（3）慢性乙型肝炎伴肝源性IGT或DM者,空腹血糖（FPG）、餐后血糖（PPG）水平均低于伴原发性DM者（P＜0.05）;但前者葡萄糖负荷后胰岛素（PINS）及C肽（PCP）分泌水平高于后者（P＜0.05）.（4）乙型肝炎后肝硬化伴肝源性DM与伴原发性DM患者的FPG、PPG水平差异均无统计学意义,伴肝源性DM患者空腹胰岛素（FINS）、PINS、空腹C肽（FCP）及PCP水平高于伴原发性DM患者（P＜0.05）,但两者的PINS/FINS、PCP/FCP值差异无统计学意义,且小于5;伴肝源性DM患者其FPG、PPG水平均显著高于伴肝源性IGT者（P＜0.05）,FINS、PINS及FCP、PCP水平均低于肝源性IGT患者（P＜0.05,P＜0.01）.结论肝病继发糖代谢异常者多发生于肝硬化患者,且以肝功能损害较重者为主,多无症状;慢性乙型肝炎伴肝源性DM患者胰岛β细胞分泌胰岛素的功能增强,而乙型肝炎后肝硬化伴肝源性DM患者则减弱.     

Biological diagnosis of the type of liver disease in alcoholic patients with abnormal liver function tests

OBJECTIVES: The histological diagnosis of the different stages of alcoholic liver disease is not systematic. The aim of this study was to assess whether common biological features were useful in identifying the different stages. METHODS: One thousand twenty six alcoholic patients with liver histology and without any associated diseases or infections likely to alter serum liver tests were studied. Diagnostic analyses were performed using stepwise discriminant analysis in the entire population and in asymptomatic patients. RESULTS: a) Serum ASAT activity levels were only normal in 39% of the patients with normal histological liver and in 14% of the patients with steatosis; b) liver failure was already present in patients with fibrosis without cirrhosis; c) betagamma block was the only biochemical parameter which confirmed the diagnosis of cirrhosis without biopsy; d) the diagnostic accuracy of common tests was weak for the diagnosis of alcoholic liver disease without cirrhosis but prothrombin time could be useful in excluding the diagnosis of cirrhosis with and without acute alcoholic hepatitis when liver biopsy is not available. CONCLUSION: Only a prothrombin time of 80% with a negative predictive value of 94% and the presence of beta-gamma [corrected] block with a positive predictive value of 98% were useful for assessing the diagnosis of cirrhosis in all patients with alcoholic liver disease.     

Isolation of an inhibitor responsible for abnormal glucose utilization in liver disease

Summary An inhibitor of glucose utilization in rat diaphragm was isolated from the serum of patients suffering from liver cirrhosis. This inhibitor is suggested to contribute to abnormal carbohydrate metabolism in liver diseases. It is a low molecular weight substance, probably of pepticle nature. It is identical with the inhibitor of glucose utilization isolated from the serum and urine of patients with renal failure and from the urine of healthy subjects.     

Severe hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver

We describe a series of cases of extreme hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver after an allogeneic bone marrow transplant. All of the patients presented with a total cholesterol in excess of 1000 mg/dl (25.9 mmol/l). At the time they were also noted to have pseudohyponatremia. Cholesterol appeared to be predominantly carried by lipoprotein X. Intrahepatic cholestasis leading to reflux of bile lipoproteins into the bloodstream and subsequent formation of protein X appears to be the mechanism underlying this phenomenon. Complications, including retinal cholesterol thromboembolism and cholesteroloma of the lung have been seen in the patient with the highest cholesterol levels. Severe hypercholesterolemia is an important, and likely more common than previously reported, long-term complication of allogeneic hematopoietic stem cell transplantation. It is important for clinicians to familiarize themselves with the diagnostic and therapeutic challenges this condition presents.     

Impaired blood rheology by remnant-like lipoprotein particles: studies in patients with fatty liver disease

Fatty liver disease (FLD) characterised by a high plasma levels of lipoproteins and remnant-like lipoproteins (RLP) is a risk factor for impaired microvascular blood flow, endothelial cell dysfunction and atherosclerosis. Using an immunoseparation technique with a gel mixture containing human monoclonal antibodies to apo A-I and apo B-100, we separated and measured RLP cholesterol (RLP-C) levels which reflect RLP in patients with FLD (n=20). Whole blood transit time (TT) was determined by a microchannel method (MC-FAN) which allows blood flow to be viewed via a microscope connected to an image display unit. RLP-C levels were higher (P<0.01) in FLD, 15.6 +/- 1.0 mg/dl compared with 4.8 +/- 0.5 mg/dl for controls (n=20). Similarly, TT was longer (P<0.01) in FLD, 284.5 +/- 26.1 sec/100 microl compared with 82.8 +/- 1.0 sec/100 microl for controls. Since the liver is a major site for RLP formation and degradation, it is affected to a greater extent in patients with FLD. It is likely that high levels of RLP can impair microvascular perfusion in the liver tissue and contribute to the development and progression of FLD.     

Ultrasonography in asymptomatic patients with abnormal biochemical liver tests

A substantial number of patients referred for ultrasound examination of the liver, biliary tract, and pancreas are asymptomatic but have abnormal biochemical liver test results. Retrospective evaluations were made of abdominal ultrasonographies in 286 such patients (159 men and 127 women). Normal studies were found in 104 of the men (65%) and 78 of the women (61%). Cholecystolithiasis with or without chronic cholecystitis was found in 24 of the men (15%) and 36 of the women (28%); diffuse liver parenchyma disease was found in 21 of the men (13%) and 7 of the women (6%). Other significant abnormalities were chronic pancreatitis (3), carcinoma of the gallbladder (2), liver metastasis (2), hepatocellular carcinoma (1), lymphoma (1), and ampullary carcinoma (1). Ultrasonography is a suitable technique for evaluation of asymptomatic patients with abnormal biochemical liver test results, and we have adopted it as the method of choice in this setting.     

Role of ERCP in asymptomatic orthotopic liver transplant patients with abnormal liver enzymes

OBJECTIVE: The safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in the evaluation and management of biliary tract complications after orthotopic liver transplantation (OLT) have been previously demonstrated. However, the role of ERCP in evaluating asymptomatic OLT patients with abnormal liver enzymes with a previously normal biliary tree remains poorly defined. We sought to assess the utility of ERCP in this subset of patients. METHODS: A retrospective analysis of-asymptomatic OLT patients with abnormal liver enzymes evaluated by ERCP was undertaken. In addition to ERCP, all these patients had a diagnostic abdominal Doppler ultrasound, and a percutaneous liver biopsy. All patients had choledochocholedochostomy at the time of transplant and normal T-tube cholangiograms 3 months postoperatively. A radiologist, blinded to clinical findings, interpreted the ultrasound as normal, biliary dilation, or vascular abnormalities. The same radiologist interpreted ERCP findings. A pathologist, blinded to clinical findings, graded liver biopsies as normal, diagnostic, or abnormal but nondiagnostic. RESULTS: Twenty-two patients underwent 23 ERCPs. Twenty-two of the 23 ERCPs were normal (96%), and one abnormal ERCP finding did not explain the liver enzyme abnormality. Liver biopsy was diagnostic in 13 of 22 (57%) and in each case the ERCP was normal. The remaining 10 liver biopsies were abnormal but nondiagnostic. Ultrasound was abnormal in five of 22 cases, but in the three cases suggesting biliary dilation, the ERCP was interpreted as normal. CONCLUSION: Routine use of ERCP in evaluation of asymptomatic OLT patients with liver function test abnormalities and normal cholangiograms at 3 months was not diagnostically useful. In this subset of patients, liver biopsy was usually abnormal and frequently diagnostic and should be the initial invasive diagnostic procedure.     

202例肝功能异常患者病因分析

目的 探讨肝功能异常的常见病因。方法 2011年6月~2018年6月收治的202例肝功能异常患者,常规进行病因筛查。结果 在202例住院的肝功能异常患者中,脂肪性肝病（NAFLD）62例（30.7%）、药物性肝损害（DILI）56例（27.7%）、自身免疫性肝病（AILD）18例（8.9%）、嗜肝病毒感染18例（8.9%）、肿瘤9例（4.5%）、肝硬化11例（5.5%）、胆道系统感染11例（5.5%）、非嗜肝病毒感染1例（0.5%）、中毒1例（0.5%）、营养不良2例（1.0%）和病因不明13例（6.4%）;青年组NAFLD、DILI和嗜肝病毒感染构成比分别为49.4%、16.9%和10.8%,中年组DILI、脂肪性肝病和AILD构成比分别为34.3%、25.4%和10.5%,老年组DILI、AILD和肿瘤构成比分别为36.5%、15.4%和13.5%;男性NAFLD、DILI和嗜肝病毒感染构成比分别为43.6%、20.0%和15.8%,女性DILI、脂肪性肝病和AILD构成比分别为35.6%、17.8%和14.9%。结论 导致肝功能异常的病因较多,不同年龄和不同性别人群常见病因有所不同。     

Association of abnormal fibrin polymerisation with severe liver disease.

The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.     

Pulmonary dysfunction in advanced liver disease: Frequent occurrence of an abnormal diffusing capacity

PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance.     

High density lipoprotein subpopulations in chronic liver disease

Severe liver disease may be associated with a reduction in plasma concentration of high density lipoprotein and an impairment of plasma cholesterol esterification. These changes were confirmed in two patients with severe acute on chronic alcoholic liver disease. In five additional patients with biopsy-proven clinically compensated cirrhosis, there was minimal reduction in concentration of plasma cholesteryl esters; there was, however a reduction of the plasma high density lipoprotein concentration to only 48 to 66% of normal. The particle size distribution of high density lipoprotein in these five patients was determined by gradient gel electrophoresis. The high density lipoprotein2 subfraction was preserved. The high density lipoprotein3 subfraction, however, was markedly changed with a reduction in the normal particles of radius 4.3 m and an accentuation of smaller particles of radius 3.9 m; in two patients, these smaller particles were the major high density lipoprotein subpopulation. Further investigations of this finding of a distinctive distribution of high density lipoprotein subpopulations in patient with chronic liver disease may provide new insights into high density lipoprotein metabolism.     

83例肝病患者临床与肝组织病理学分析

目的通过对83例肝病患者的临床与肝组织病理学检查的对比研究,以提高临床诊断的准确性。方法用全自动生化分析仪进行血清生化指标检测,ELISA法检测HBV血清标志物,同时进行肝组织病理检查,检测肝组织HBsAg和HBcAg的表达。结果51例血清HBsAg阳性者肝细胞中均有HBsAg和/或HBcAg表达,32例血清HB-sAg阴性者有9例(28.1%)肝组织中有HBsAg和/或HBcAg表达。75例慢性肝病患者中ALT在各炎症分级组间差异无统计学意义(P>0.05),AST和TBIL在不同的肝脏炎症分级组间差异有统计学意义(P<0.05),且炎症分级越高,AST和TBIL升高越明显;ALT、AST、TBIL值在肝脏纤维化S2期最高。以病理诊断为标准,临床慢性肝炎轻度和中度的诊断准确率分别为61.9%(13/21)和62.5%(20/32),肝硬化的临床诊断准确率为40%。结论以肝组织病理检查为金标准,肝病临床诊断的准确率仍较低。为提高慢性肝病的临床确诊率,应尽可能行肝组织病理学检查。     

Metabolic bone disease in patients with liver disease

The coexistence of liver disease and osteopenic bone disease has been recognized for many years and is now the subject of increasing attention. Osteoporosis has been characterized well in patients with cholestatic liver disease, but new research suggests that osteopenia and osteoporosis may also be prevalent in patients with other chronic liver diseases. Although the precise mechanism of bone loss remains unclear, advances in treatment and prevention are bringing heightened awareness to this common problem.     

肾脏病患者脂蛋白（a）异常的初步研究

采用恒电位暂态和旋转盘环电极等方法研究了α、α＋β以及β黄铜在硫酸钠、硫酸以及氯化钠的稀溶液中的阳极溶解过程，结果表明，在黄铜阳极溶解的初始阶段测得的ｉ－ｔ曲线遵循抛物线定律，求得ｉ－ｔ＾－１／２为一通过坐标原点的直线，证明了黄铜中锌的选择性溶解受固相扩散控制，计算出在上述溶液中黄铜中锌的扩散系数值在１０＾１５～１０＾－１３ｃｍ＾２．Ｓ＾－１数量级，介质成分和微量合金元素砷对扩散系值有明显的影响。     

Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia.

Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low-density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation.     

High-density lipoprotein cholesterol in male alcoholics with and without severe liver disease

In a study of 26 male alcoholics, the subgroup without severe liver disease showed significant elevation in high-density lipoprotein cholesterol (HDL) in the immediate post-intoxication period; HDL levels decreased to control levels after one to two weeks of abstinence. Those patients with advanced liver disease failed to show this ethanol-induced rise in HDL. We were not able to correlate these observations with any variation in sex hormone levels, nutritional indices, age or quantity of alcohol intake. We concluded that ethanol consumption in alcoholics is associated with an increase in HDL levels, which is offset by the development of alcoholic liver disease.