8181名体检者中HBV血清学标志物与ALT的检测分析

目的:了解东莞市体检人群中乙肝病毒(HBV)感染情况与血清丙氨酸氨基转移酶(ALT)的异常率。方法:对8181名体检者应用酶联免疫吸附法(ELISA)法测定HBsAg、HBsAb、HBeAg、HBeAb、HBcAb,用速率法测定ALT。结果:HBsAg的阳性率为13.14%,HBeAg的阳性率为4.89%,ALT的异常率为3.40%。乙型肝炎病毒血清学标志物主要以HBsAg、抗-HBe、抗-HBc阳性和HBsAg、HBeAg、抗-HBc阳性的两种模式为主。结论:东莞市体检者中的HBsAg的阳性率高于全国的HBsAg的阳性率,其中HBsAg阳性率20岁以下相对低些,20岁~30岁的高达17.19%,HBeAg的阳性率在20岁~30岁的打工者中占较大比例。其人群分布与计划免疫、文化程度、卫生习惯、生活环境等因素有关。     

Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease

OBJECTIVE: To examine the role of metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease. STUDY DESIGN: In 50 obese children (age 7 to 14 years) with (n = 20, group 1) or without (n = 30, group 2) hypertransaminasemia and ultrasonographic liver brightness, we studied insulin resistance (fasting glucose/insulin ratio [FGIR]) and serum levels of leptin, iron, transferrin, ferritin, C-reactive protein (CRP), white blood cell (WBC) count, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, C282Y and H63D mutations, and erythrocytic glutathione peroxidase (GPX) activity. RESULTS: FGIR (6.7 +/- 4.1 vs 9.2 +/- 5.2; P = .02), serum ferritin (88.8 +/- 36.0 vs 39.9 +/- 24.0 ng/mL; P = .0001), serum CRP (5.4 +/- 6.0 vs 1.1 +/- 1.6 mg/dL; P = 0.004), and GPX (8.4 +/- 0.9 vs 5.0 +/- 0.5 U/g Hb; P = .05) were significantly higher and more frequently deranged in group 1 than in group 2. FGIR, ferritin, and CRP values were simultaneously deranged in 41% of the group 1 patients and in none of the group 2 patients ( P = .098). Serum leptin, iron, and transferrin, WBC, TNF-alpha, IL-6, and C282Y and H63D mutations were similar in the 2 groups. CONCLUSIONS: Insulin resistance, oxidative stress, and low-grade systemic inflammatory status are implicated in pediatric obesity-related liver disease. These findings may be useful in planning pathophysiologically based therapeutic trials for hepatopathic obese children who are unable to follow hypocaloric diets.     

Liver volume in thalassaemia major: relationship with body weight,serum ferritin,and liver function

Background: It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in -thalassaemia major patients, who frequently have iron overload and hepatitis. Objective: The hypothesis is that liver volume in children and adolescents suffering from -thalassaemia major is affected by ferritin level and liver function. Materials and methods: Thirty-five -thalassaemia major patients aged 7–18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Results: Body weight explained 65 and 86% of the change in liver volume in -thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P<0.001) in thalassaemia major patients than in control subjects. There was a significant correlation between ALT level and liver volume/kilogram body weight (r=0.55, P=0.001). Patients with elevated ALT had significantly higher liver volume/kilogram body weight (mean 42.9±12 cm³/kg) than control subjects (mean 23.4±3.6 cm³/kg) and patients with normal ALT levels (mean 27.4±3.6 cm³/kg).Conclusions: Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT.     

Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain

We describe here five F7 mutations found in four patients without bleeding history, despite constitutional coagulation Factor VII (FVII) deficiency. All five mutations are missense and affect the catalytic domain of FVII (A191T, A191V, T239P, R224Q and M298I). The A191V and T239P mutations are novel and were found in homozygous patients with no clinical bleeding tendency. The patient diagnosed with the A191V mutation had a phenotype corresponding to a moderate type 1 FVII deficiency (FVII:C 4%, FVII:Ag 5%). The T239P mutation was found in a patient with mild type 2 FVII deficiency (FVII:C 25%, FVII:Ag 95%). Novel mutations are both in close vicinity to the charge-stabilizing system of FVII. Modeling studies allow understanding in part the molecular basis for the loss of function.     

Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger

OBJECTIVE: To test the hypothesis that there is an improved response to interferon in children with chronic hepatitis B (HBV) who are < or =5 years of age. STUDY DESIGN: Retrospective chart review of 22 consecutive children with chronic HBV (ages 17 months to 17 years; median, 83.9 months; 14 male, 8 female) treated with interferon-alpha2b. RESULTS: Ten patients (48%) responded to treatment [HBeAg (-), Anti-HBe (+), HBV DNA (-), HBsAg (+) and normal alanine aminotransferase/aspartate aminotransferase (ALT/AST) at 6 months after treatment], and 5 seroconverted HBsAg [above plus HBsAg negative and anti-HBs (+)]. Seven of 9 patients (78%) < or =5 years of age responded (5 cleared HBsAg). Three of 13 patients (23%) >5 years of age responded. Patient age at treatment was significantly lower in responders (63 +/- 70 months) versus nonresponders (104 +/- 55 months, P =.005). AST, ALT, and HBV DNA at the start of treatment were not different between responders and nonresponders or between patients < or =5 and >5 years old. CONCLUSIONS: Interferon treatment may be more effective in younger children with chronic hepatitis B.     

Reduced acetylcholinesterase activity in erythrocyte membranes from patients with phenylketonuria

OBJECTIVE: a) To evaluate acetylcholinesterase (AChE) activities in erythrocyte membranes from phenylketonuric (PKU) patients and controls and to correlate with their plasma phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA) levels. b) To determine the in vitro effects of Phe, Ala and Phe plus Ala on their AChE activities. DESIGN AND METHODS: AChE activities were determined spectrophotometrically in erythrocyte membranes from PKU children (n = 12) adhering to their diet (group A), from 11 "off diet" (group B) and from 23 controls. Their plasma amino acids were evaluated with an amino acid analyser and DA with an HPLC method. Ala (1.8 mM) and/or Phe (1.8 mM) were added in the enzyme incubation medium from controls, whereas only Ala was added in that from group B. RESULTS: AChE activity (1.19 +/- 0.05 deltaOD/min x mg protein), Tyr (46 +/- 17 micromol/L) and DA (56 +/- 18 micromol/L) were remarkably decreased by about 60% in group B as compared to those of group A (3.01 +/- 0.18 deltaOD/min x mg protein, 115 +/- 39 micromol/L, 137 +/- 29 micromol/L, respectively, p < 0.001) and controls (3.13 +/- 0.16 deltaOD/min x mg protein, 117 +/- 44 micromol/L, 142 +/- 22 micromol/L, respectively, p < 0.001). Phe negatively correlated with AChE activity and positively with plasma Tyr and DA. Ala reversed the inhibited AChE by Phe in erythrocyte membranes from healthy children to control values, whereas no reverse effect was observed on the enzyme activity from PKU patients. CONCLUSIONS: a) The low levels of DA and its precursor Tyr are due to the high Phe blood levels, as a consequence of the decreased activity of Phe-hydroxylase in the liver of our patients. So, high Phe blood levels inhibit AChE in PKU patients, probably resulting in higher acetylcholine concentrations. b) Determination of AChE in erythrocyte membranes from PKU could be a useful marker for the neurotoxic effects of Phe.     

The activities of alanine aminopeptidase,leucine aminopeptidase,proline dipeptidase and prolyl dipeptidase in the mucosa of the small intestine

Alanine aminopeptidase (EC 3.4.11.2), leucine aminopeptidase (EC 3.4.11.1), proline dipeptidase (EC 3.4.13.9), and prolyl dipeptidase (EC 3.4.13.8) have been investigated in small intestinal mucosa homogenates of normal children and children suffering from different degrees of villous damage. The activities of proline dipeptidase and prolyl dipeptidase could be shown to be significantly decreased in cases of subtotal and total villous atrophy, whereas the activities of alanine aminopeptidase and leucine aminopeptidase were not influenced. The results are discussed in view of the subcellular distribution of these enzymes.     

The effects of oral alanine administration on blood glucose,pyruvate, lactate,serum glucagon and insulin in human newborns

Alanine (500 mg/kg body weight) was given orally to 27 healthy full term newborn infants, and the changes in blood glucose, pyruvate, lactate, alanine, glucagon and insulin were determined.Significant increments in blood glucose were found in 15 infants with blood glucose levels below 60 mg/100 ml, 4 of whom showed significant elevation of serum glucagon levels on day 1. This observation suggests that hepatic gluconeogenesis is possible immediately after birth.     

丙氨酸氨基转移酶水平对FibroTouch检测慢性乙型肝炎患者肝脏硬度值的影响研究

背景　多项研究表明丙氨酸氨基转移酶（ALT）水平升高可导致肝脏硬度值（LSM）升高，但少有研究探讨不同程度升高的ALT水平尤其是轻度升高的ALT水平对慢性乙型肝炎患者（CHB）LSM的影响。目的　明确ALT水平对FibroTouch检测CHB患者LSM的影响。方法　选取2016年5月至2019年3月就诊于大连医科大学附属第二医院感染科病房的CHB患者145例，根据ALT水平分为A组〔ALT<1×参考值上限（ULN）〕46例、B组（1×ULN≤ALT<2×ULN）64例、C组（2×ULN≤ALT<5×ULN）35例。所有患者接受肝脏穿刺活检和FibroTouch检查，参照METAVIR计分系统标准将肝脏穿刺活检结果分为轻微肝纤维化（F1）、明显肝纤维化（F2~F3）、肝硬化（F4）。比较不同ALT水平、肝纤维化程度CHB患者LSM；以肝脏穿刺活检结果为“金标准”，绘制受试者工作特征（ROC）曲线以分析FibroTouch对CHB肝纤维化程度的诊断效能。结果　A组、B组患者总体LSM及F1、F2~F3、F4患者LSM均低于C组（P<0.05）。A组患者中16例为F1，22例为F2~F3，8例为F4；B组患者中14例为F1，44例为F2~F3，6例为F4；C组患者中6例为F1，22例为F2~F3，7例为F4。A组、B组、C组中F1患者LSM分别低于F2~F3、F4患者，F2~F3患者LSM分别低于F4患者（P<0.05）。Spearman秩相关分析结果显示，三组患者总体LSM均与肝纤维化程度呈正相关（rs值分别为0.81、0.71、0.73，P<0.001）。绘制ROC曲线发现，FibroTouch诊断总体、A组、B组、C组患者F2~F3的曲线下面积（AUC）分别为0.904、0.933、0.914、0.897，诊断总体、A组、B组、C组患者F4的AUC分别为0.942、0.954、0.989、0.949（P<0.001）。结论　ALT<2×ULN时FibroTouch检测CHB患者LSM不受明显影响，而ALT≥2×ULN时FibroTouch检测CHB患者LSM可能被高估，不一定能反映真实肝纤维化程度。