慢性肝病患者血清精氨[基]琥珀酸裂合酶的变化

目的建立自动生化分析仪检测血清精氨[基]琥珀酸裂合酶（ASL）的方法,探讨其对慢性肝病的诊断效能。方法测定149例慢性肝病患者、247例非肝病患者和32例健康对照血清ASL活性,同时测定ALT和AST活性。结果本组病例ASL、ALT和AsT水平与健康对照间均存在明显差异;对照组与非肝病患者ASL活性无明显差异（q=0．051,P=0．959）;慢性肝病组与非肝病组、健康对照组ASL活性无重叠。ROC曲线显示ASL对判断慢性肝病的敏感性为98．7％,特异性为97．5％（cutoff值=9．2U／L）;ALT、AST的敏感性为60．4％和57．7％,特异性仅分别为33．4％和36．6％（cutoff值：40．0U／L）。结论ASL诊断慢性肝病的敏感性和特异性均优于AsT和ALT,是慢性肝病诊断的有用指标。     

血清视黄醇结合蛋白检测对2型糖尿病患者早期肾功能损伤诊断的价值

目的应用受试者工作特征(ROC)曲线评价血清视黄醇结合蛋白(RBP)检测在2型糖尿病(T2DM)早期肾功能损伤中的应用价值。方法将155例临床确诊为T2DM的患者按照尿微量清蛋白(mAlb)/尿肌酐(UCr)比值分为单纯糖尿病组、早期糖尿病肾病组和临床糖尿病肾病组;另外选取同一时期进行健康体检且合格者作为对照组;比较各组间的差异,同时通过ROC曲线评价RBP在糖尿病早期肾功能损伤中的诊断价值。结果早期糖尿病肾病组与对照组、单纯糖尿病组比较,RBP水平差异均有统计学意义(P0.05);血清RBP的ROC曲线下面积为0.770,灵敏度和特异度分别为81.0%、95.2%。结论 RBP检测有助于发现糖尿病患者早期肾功能损伤。     

肝硬化判别评分诊断慢性乙型病毒性肝炎肝纤维化的临床价值

目的:探讨肝硬化判别评分诊断慢性乙型病毒性肝炎肝纤维化的临床价值。方法:172例慢性乙型病毒性肝炎患者均接受肝组织病理检查,并同时检测肝功能、血常规和凝血功能,用ROC曲线评价肝硬化判别评分诊断无或轻度肝纤维化(S0/S1)、显著肝纤维化(S2/S3/S4)、严重肝纤维化(S3/S4)和肝硬化(S4)的能力。结果:S4的肝硬化判别评分明显高于S0、S1、S2和S3(P<0.01);肝纤维化分期和肝硬化判别评分的相关系数rs=0.375(P<0.01);肝硬化判别评分诊断显著肝纤维化的ROC曲线下的面积0.726,阳性预测值95.3%,肝硬化的AUC 0.814,阴性预测值96.5%,严重肝纤维化的AUC仅有0.626,敏感度38.8%。结论:肝硬化判别评分和肝纤维化分期有一定的相关性,肝硬化判别评分可以用于评估慢性乙型病毒性肝炎患者有无显著肝纤维化或肝硬化,但对S2和S3的区分能力有限。     

酶抑制法测定m-AST试剂性能评价及其在肝病中的意义

目的评价酶抑制法测定天门冬氨酸氨基转移酶（AST）线粒体同工酶（m—AST）活性的性能,并探讨m—AST在肝脏疾病中的临床价值。方法采用酶抑制法检测m—AST活性[即采用蛋白酶完全抑制AST细胞质同工酶（c—AST）的活性,然后用速率法进行检测],并与免疫抑制法比较。采用酶抑制法检测259例肝病患者（包括急性肝炎43例、慢性病毒性肝炎95例、肝衰竭20例、重型肝炎11例、肝硬化代偿期40例、肝硬化失代偿期9例、原发性肝癌41例）及220名健康体检者（正常对照组）m—AST活性,并与AST比较。结果酶抑制法批内变异系数（CV）为0．59％～2．23％,批间CV为5．24％～6．23％;回收率为101．6％～108．0％,平均为104．97％;线性方程Y=0．997X一1．51,r=0．9999,m—AST活性在450U／L内线性良好;可完全抑制1500U／L的c—AST活性;与免疫抑制法结果呈高度正相关（r=0．9998）;溶血对m—AST检测结果干扰较大;以95％可信区间（孟±1．96s）初步确定m—AST参考区间男性为3．1～9．5U／L,女性为2．5～8．7U／L。肝病患者m—AST活性均高于正常对照组（P〈0．05）,并与AST呈正相关。正常对照组m—AST／AST比值为0．30±0．07,肝病患者m—AST／AST比值均低于正常对照组（P〈0．05）,但变化不如m—AST活性明显。结论酶抑制法测定m．AST活性自动化程度高,结果准确可靠,重复性好,线性范围宽。m—AST活性能反映肝细胞损伤的严重程度,对肝脏疾病的临床分类和预后具有重要价值。     

谷氨酸脱氢酶、胆碱酯酶在高血清丙氨酸转氨酶肝病患者鉴别诊断中的应用

目的探讨谷氨酸脱氢酶(GDH)、胆碱酯酶(CHE)在高血清丙氨酸转氨酶(ALT)患者鉴别诊断中的应用价值。方法收集103名健康者和108例高ALT患者的血清标本,在BayerADVIA1650型全自动生化分析仪上同时测定GDH、CHE的活性。结果在急性病毒性肝炎、急性缺血性肝炎、急性中毒性肝坏死时GDH均明显升高,与正常对照组差异有显著性(P<0.01),其中以急性缺血性肝炎升高的幅度最大,其和急性中毒性肝坏死的阳性率均可达100%。CHE只有在急性中毒性肝坏死时才明显下降(P<0.01)。结论联合检测GDH、CHE活性将有助于鉴别诊断高血清ALT肝病患者,对指导临床治疗具有重要意义。     

谷氨酸脱氢酶、胆碱酯酶在高血清丙氨酸转氨酶肝病患者鉴别诊断中的应用

目的 探讨谷氨酸脱氢酶（GDH）、胆碱酯酶（CHE）在高血清丙氨酸转氨酶（ALT）患者鉴别诊断中的应用价值.方法 收集103名健康者和108例高ALT患者的血清标本,在Bayer ADVIA1650型全自动生化分析仪上同时测定GDH、CHE的活性.结果 在急性病毒性肝炎、急性缺血性肝炎、急性中毒性肝坏死时GDH均明显升高,与正常对照组差异有显著性（P〈0.01）,其中以急性缺血性肝炎升高的幅度最大,其和急性中毒性肝坏死的阳性率均可达100%.CHE只有在急性中毒性肝坏死时才明显下降（P〈0.01）.结论 联合检测GDH、CHE活性将有助于鉴别诊断高血清ALT肝病患者,对指导临床治疗具有重要意义.     

Assessing routine and serum markers of liver fibrosis in CHB patients using parallel and serial interpretation

OBJECTIVE: The purpose of this study was to determine the cut-offs of serum biomarkers of liver fibrosis in HBsAg-positive patients by receiver operating characteristic (ROC) curves, and to determine the validity of these markers in parallel and serial interpretation. METHODS: This study included 444 HBsAg-positive patients who had liver biopsy performed between January 1, 2003 and March 31, 2006. Some routine and clinical chemistry tests were run, and the stage of liver fibrosis was measured. The cut-offs of those markers were identified by using ROC curves. Sensitivity, specificity, predictive values (both positive and negative), and the Youden's index of these markers were calculated in parallel and serial interpretation. RESULTS: The 444 patients were divided into a training group (322 patients) and a validation group (122 patients). All markers except gender, HB and TP were found to be statistically significant factors associated with significant fibrosis in the training group. The AUROC of GGT, APRI, AGE-PLT and AST in the training group were 0.772, 0.769, 0.748 and 0.700, respectively, and their sensitivities in the validation group were 65.00%, 70.00%, 75.00% and 60.00%, respectively. In parallel interpretation, the highest sensitivity was 85.00% at AGE-PLT union or logical sum AST, and in serial interpretation, the best specificity was 96.34% at GGT intersection AGE-PLT. CONCLUSION: A few routine and serum biomarkers can be used to effectively assess most patients with HBsAg-positive CHB with and without significant liver fibrosis in parallel and serial interpretation.     

Risk prediction for Down's syndrome in young pregnant women using maternal serum biomarkers: determination of cut-off risk from receiver operating characteristic curve analysis

OBJECTIVE: The aim of this study was to establish a predictive model for Down's syndrome using maternal age as well as maternal serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and to identify an optimal cut-off risk in women under the age of 35 years to improve sensitivity. METHODS: Logistic regression models were utilized to predict fetal Down's syndrome as a function of maternal age and logarithm of levels of AFP as well as hCG using training data of 20 pregnancies with fetal Down's syndrome and 9730 unaffected pregnancies. Validation was performed using data of another nine affected pregnancies and 3496 unaffected pregnancies. Receiver operating characteristic (ROC) curves were plotted. RESULTS: Based on the newly established logistic regression equations, the optimal cut-off risk from the ROC curve analysis was at 1:499, with a 17.8% false-positive rate and a 90.0% sensitivity. A suboptimal cut-off risk was estimated at 1:332, with a 12.0% false-positive rate and an 80% sensitivity. CONCLUSION: A predictive model for Down's syndrome was developed using logistic regression. By ROC curve analysis and clinical consideration, the cut-off risk for young pregnant women could be determined.     

Fructose 1,6-bisphosphatase in the diagnosis of chronic hepatitis. II. Classification of chronic hepatitis based on fructose 1,6-bisphosphatase and other laboratory data

The histomorphology of typical liver cell necroses are here correlated with heterotope distributions of enzymes in liver parenchyma. A variety of findings indicate a congruence between gluconeogenetic areas of the liver and the typical pattern of 'piecemeal' necrosis. We therefore propose a diagnostic index based on fructose 1,6-bisphosphatase activity and the data from the clinical laboratory. This index makes it possible to distinguish between chronic persistent and chronic aggressive hepatitis.     

Diagnostic accuracy of serum asialo-alpha1-acid glycoprotein concentration for the differential diagnosis of liver cirrhosis and hepatocellular carcinoma

BACKGROUND: Serum asialoglycoproteins concentration are increased in patients with hepatic disease. We developed an antibody-lectin sandwich assay that is sensitive and specific to measure asialo-alpha(1)-acid glycoprotein (AsAGP) concentration in human serum and evaluated it as a biochemical marker for hepatic disease. METHODS: Serum AsAGP concentration was measured by antibody-lectin sandwich assay with 610 serum specimens of patients with hepatic disease. Serum from 41 healthy donors and 155 patients with non-hepatic disease served as negative controls. The AsAGP values were analyzed by receiver operator characteristics (ROC) curve analysis. The diagnostic accuracy of AsAGP value was compared with those of the conventional biochemical markers in the liver function test. RESULTS: Serum AsAGP concentration in 83% of patients with liver cirrhosis (LC) and 89% of patients with hepatocellular carcinoma (HCC) was increased over the cutoff value (1.33 microg/ml), indicating that an increase of serum AsAGP concentration is restricted to LC or HCC cases. The area under curve (AUC) in the ROC curve was 0.919 for LC and 0.946 for HCC. CONCLUSIONS: Serum AsAGP concentration exhibited good diagnostic accuracy as a biochemical marker for LC and HCC. The addition of AsAGP to conventional liver function tests may significantly improve the diagnosis and prognosis.     

Serum levels of pigment epithelium-derived factor (PEDF) are independently associated with procollagen III N-terminal peptide levels in patients with nonalcoholic fatty liver disease

Objectives

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with complex anti-oxidative, anti-fibrotic, and anti-inflammatory properties, thus being involved in cardiometabolic disorders. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome as well. However, the pathophysiological role of PEDF in NAFLD remains largely unknown. We studied here the relationship between serum PEDF levels and various clinical markers of NAFLD in humans.

Design and methods

The study involved 194 biopsy-proven NAFLD patients (102 male and 92 female) with a mean age of 51.3 ± 13.8 years. We examined which anthropometric, metabolic and inflammatory variables, and liver steatosis and fibrosis markers are independently associated with serum levels of PEDF.

Results

Mean serum levels of PEDF were 16.4 ± 5.7 μg/mL. Univariate analysis revealed that age (inversely), male, body mass index, waist circumference, numbers of white blood cells and platelets, aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, glycated hemoglobin, uric acid, procollagen type III N-terminal peptide (P-III-P), subcutaneous fat areas, visceral fat areas and liver to spleen density ratio in computed tomography, the presence of diabetes and medication for hyperlipidemia were significantly associated with serum levels of PEDF. In multiple stepwise regression analysis, age (p < 0.01, inversely), male (p < 0.05), waist circumference (p < 0.01), white blood cell number (p < 0.05), P-III-P (p < 0.05), and the presence of diabetes (p < 0.05) and medication for hyperlipidemia (p < 0.01), were independently correlated to serum levels of PEDF (R² = 0.285).

Conclusions

The present study reveals that serum levels of PEDF are independently associated with P-III-P levels, suggesting that PEDF level is a novel biomarker of liver fibrosis in patients with NAFLD.     

The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease,Langerhans Cell Histiocytosis,and Rosai-Dorfman Disease

Histiocytic neoplasms, a rare and heterogeneous group of disorders, primarily include Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Due to their diverse clinical manifestations, the greatest challenge posed by these neoplasms is the establishment of a diagnosis, which often leads to a delay in institution of appropriate therapy. Recent insights into their genomic architecture demonstrating mitogen-activated protein kinase/extracellular signal–regulated kinase pathway mutations have now enabled potential treatment with targeted therapies in most patients. This consensus statement represents a joint document from a multidisciplinary group of physicians at Mayo Clinic who specialize in the management of adult histiocytic neoplasms. It consists of evidence- and consensus-based recommendations on when to suspect these neoplasms and what tests to order for the diagnosis and initial evaluation. In addition, it also describes the histopathologic and individual organ manifestations of these neoplasms to help the clinicians in identifying their key features. With uniform guidelines that aid in identifying these neoplasms, we hope to improve the awareness that may lead to their timely and correct diagnosis.     

Clinical characteristics of Japanese patients with moderate to severe COVID-19

IntroductionAlthough several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient’s characteristics whose disease progressed to severe status.MethodsThe medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1–4 L/min), and severe diseases (oxygen needs of 5 L/min or more).ResultsThe median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL.ConclusionsAge and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.