慢性乙型肝炎血清HBV DNA水平与血清ALT的关系

目的探讨慢性乙型肝炎病毒(HBV)复制水平与丙氨酸氨基转移酶(ALT)之间的关系。方法对180例慢性乙型肝炎患者血清HBV DNA含量采用荧光标记(AmpliSensor)定量PCR方法检测,并比较HBV DNA含量与ALT的关系。结果慢性乙型肝炎轻度、中度患者HBV DNA含量(105.58±1.92,106.27±2.05)与慢性乙型肝炎重度患者HBV DNA含量(105.73±1.90)相比较差异无统计学意义(P>0.05),且不同HBV DNA水平患者的ALT差异无统计学意义(P>0.05)。结论随着肝损害程度的加重,慢性乙型肝炎患者血清HBV DNA基因含量未发生显著变化,同时血清HBV DNA含量与ALT水平无明显关系。     

安慰剂与住院时间对转氨酶的影响

目的观察住院时间10天以上并多次服用安慰剂后的健康志愿者引起的转氨酶变化趋势。方法在2个新药I期临床试验中，对多次服用安慰剂、住院时间为2天或13天的16名健康志愿者多次进行转氨酶检查。结果住院时间为13天且多次服用安慰剂的受试者，ALT呈逐渐升高的趋势；但AST无明显变化。多次服用安慰剂但住院时间为2天的受试者，ALT和AST均无明显变化。结论对住院时间长的新药I期临床试验，应考虑安慰剂可能引起的转氨酶升高，避免在判断试验药物是否产生肝损害时，出现偏差。     

乙型肝炎患者体内病毒复制水平的试验观察

目的探讨乙肝病毒感染者体内血清标志物与乙肝病毒脱氧核糖核酸（HBV—DNA）和转氨酶的相互关系及其临床意义。方法采用酶联免疫吸附试验（ELISA）检测HBV血清标志物，采用实时荧光定量PCR方法检测HBV—DNA，采用速率法测定血清内的转氨酶。结果随着病毒复制水平的增加，“大三阳”的检出率具有逐渐增加的趋势，而“小三阳”的检出率具有逐渐减少的趋势；“大三阳”与患者体内血清转氨酶异常检出率显著高于“小三阳”；在“小三阳”中，当HBV—DNA大于10^5时，转氨酶异常者的检出率显著增加，而“大三阳”中没有观察到该结果。结论“大、小三阳”可作为HBV复制和疾病进展评估的参考指标。     

落新妇苷通过促进IL-10表达保护小鼠缺血再灌注损伤肝脏

目的:观察落新妇苷对肝脏热缺血再灌注损伤的保护作用,对其机制进行初步探讨。方法:C57BL/6小鼠随机分为4组：假手术组(Sham)、模型组(I/R)、落新妇苷小剂量(10 mg/kg)干预组和落新妇苷大剂量(40 mg/kg)干预组。缺血前24 h和1 h干预组小鼠腹腔注射分别给予10或40 mg/kg的落新妇苷,建立肝左、中叶70％部分肝缺血再灌注模型,模型组和假手术组给予同样体积的生理盐水。小鼠肝脏左叶缺血90 min、再灌注6 h后各实验组采集血液和肝脏组织样本。检测血清中丙氨酸转氨酶(ALT)的活性作为肝功能损伤的指标,同时用ELISA检测肝组织中MPO含量。观察肝脏组织病理学改变。Western印迹检测肝组织中IL-10蛋白含量,半定量RT-PCR检测IL-10 mRNA表达情况。结果:落新妇苷干预能有效降低部分肝脏热缺血再灌注小鼠血清ALT水平,能有效降低缺血肝脏中MPO含量,改善肝组织病理表现。干预组肝组织中IL-10蛋白表达与I/R模型对照组比较均渐次升高,与半定量RT-PCR结果相符(小剂量干预组P<0.05；大剂量干预组P<0.01)。结论:落新妇苷干预能减轻小鼠肝脏热缺血再灌注损伤后的炎症反应,有效改善肝功能和肝脏病理损害；机制可能在于其能促进缺血再灌注损伤肝组织中IL-10的高表达。     

住院患儿转氨酶升高的回顾性分析

目前在临床上药物性损伤已非常普遍。现对1242例住院患儿（非肝病科患儿）和953例健康儿童的谷丙特氨酶和谷草特氨酶进行了回顾性对比统计，发现住院患儿的谷丙特氨酶和谷草转氨酶大于40IU／L以上的所占比例分别为26．08％和31％。而健康儿童的谷丙特氨酶和谷草特氨酶大于40IU／L以上的所占比例分别为3．99％和3．16％。因此，在住院患儿和健康儿童中存在着显著性差异。     

Relationship of clinical and virological factors with hepatitis activity in hepatitis B e antigen-negative chronic hepatitis B virus-infected patients

To investigate the factors associated with active disease among hepatitis B surface antigen (HBsAg) positive/hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection we studied chronic HBV infected patients who had undetectable HBeAg at the first visit. HBV DNA was determined by the cross-linking assay (NAXCOR) and polymerase chain reaction (PCR). Mutations in the core promoter and precore regions and viral genotypes were studied. Clinical outcome of these patients were followed and categorized as: (i) relapse (ALT > 200 IU/L or three times the previous levels); (ii) active hepatitis (elevated ALT < 200 IU/L with concomitant detectable HBV DNA); or (iii) remission. A total of eighty-five patients were followed up for 5.5 ± 1.0 years. At first visit, 31 (36.5%) patients had elevated ALT levels, 12 (14.1%) had measurable HBV DNA by the cross-linking assay and 26 (30.6%) by PCR. Sixteen (18.8%) patients had hepatitis relapse, 13 (15.3%) had active hepatitis, and 56 (65.9%) remained in remission. Core promoter and precore stop codon mutants were found in 27 and 12 patients, respectively. Eleven and 20 had genotype B and C HBV, respectively. Initial elevated ALT and detectable HBV DNA were associated with active liver disease. Patient demographics, viral mutants or genotypes failed to predict disease activity. Hence, serum ALT and HBV DNA levels offer the best prediction of natural course of HBeAg-negative chronic HBV infection.     

苍耳子对小鼠血清氨基转移酶及肝脏丙二醛含量的影响

目的:观察不同剂量苍耳子对小鼠体重、血清氨基转移酶及肝组织中丙二醛含量的影响。方法:60只昆明种小鼠分为4组,每组15只。分别灌服苍耳子粉状提取物(1g相当15g生药)1.04g/kg(低剂量组)、5.2g/kg(中剂量组)、20.8g/kg(高剂量组)和等体积生理盐水(对照组),连续给药4周,给药过程中每周测体重、血清氨基转移酶并检测肝组织匀浆中丙二醛的含量。结果:各给药组在第2周后出现体重增长减慢,其中高剂量组在第3周出现负增长,第4周各给药组均出现体重的负增长。各给药组的体重总增加量均显著低于对照组(P<0.05或P<0.01);苍耳子高剂量组天冬氨酸氨基转移酶高于对照组,差异有统计学意义(P<0.05);苍耳子各给药组丙二醛含量均明显高于对照组,高剂量组与对照组相比P<0.001,低、中剂量组与对照组相比P<0.05。结论:苍耳子可能影响消化系统功能,使肝脏组织的天冬氨酸氨基转移酶升高并对肝脏有脂质过氧化损伤的作用。     

凝血酶原时间测定在乙型病毒性肝炎患者中的临床应用

目的　了解凝血酶原时间(PT)、国际标准化比值(INR)及凝血酶原活动度(PTA) 3项指标在乙型病毒性肝炎(乙肝)各型患者中的分布情况,及血清丙氨酸转氨酶(ALT)对乙肝患者诊断和治疗的指导作用。方法　对某院5 33例乙肝患者及4 0例健康对照者(对照组) ,采用ACL 2 0 0型凝血仪及配套试剂测定PT ,INR及PTA值,采用贝克曼CX 9生化仪及配套试剂测定ALT值;数据以平均数和标准差进行方差分析和q检验。结果　PT ,INR ,PTA及ALT在对照组和各型乙肝患者组经方差分析,差异有统计学意义(P <0 .0 1) ;在各型乙肝患者组经q检验,两两比较分析其组间差异性,PTA ,INR及ALT比PT更多见。结论　PT ,INR ,PTA及ALT 4项指标可以反映乙肝患者病情的严重程度,也可作为其病程变化和预后的指标。     

Studies on the mechanism of paracetamol-induced protection against paracetamol hepatotoxicity.

In rats, 3 days treatment with paracetamol (1 oral dose of 1 g/kg daily) produced a complete protection against the hepatotoxic actions of a further dose of paracetamol as documented by determination of serum enzyme activities (glutamic-oxaloacetic transaminase, (GOT), glutamic-pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), bromsulphthalein retention and histological investigations. Subacute paracetamol treatment decreased liver glutathione levels by 46%, liver microsomal cytochrome P-450 content by 23%, hepatic hydroxylation of aniline by 29% and hepatic demethylation of aminopyrine by 46%. It afforded also some protection against the hepatotoxic actions of carbon tetrachloride, bromobenzene and thioacetamide, but did not influence the antiphlogistic activity of paracetamol (carrageenan paw edema test). Plasma and liver concentrations of free paracetamol after oral administration of 1 g/kg paracetamol were somewhat higher in the subacutely paracetamol-pretreated rats than in the non-pretreated control animals whereas no differences in the concentrations of conjugated paracetamol were found between the 2 groups. Pretreatment with paracetamol did not influence the urinary excretion of free paracetamol but caused some shift in the urinary excretion of paracetamol conjugates: pretreated rats excreted 23% less of the paracetamol glucuronide and sulfate and 33% more of the paracetamol mercapturate than the control animals. A depression of the microsomal mixed-function oxidase activity is presumed to be the main cause of the paracetamol-induced protection against paracetamol hepatotoxicity.     

N-acetylcysteine-induced inhibition of gastric emptying: A mechanism affording protection to mice from the hepatotoxicity of concomitantly administered acetaminophen

Swiss Webster male mice, 22 ± 3 g, killed 17–18 h following the concomitant oral administration of acetaminophen (350 mg/kg) and N-acetylcysteine (NAC, 100–500 mg/kg, treated) had statistically significant lower plasma transaminases (GOT and GPT) than control mice (acetaminophen + water). Possible mechanisms underlying this protective effect of NAC were examined. NAC (500 mg/kg) reduced [¹⁴C]acetaminophen-derived radioactivity in the blood and tissues but increased the percentage of the dose in the gastrointestinal tract. Depletion of hepatic sulphydryl compounds below 75% of the control value was prevented by NAC treatment, whereas urinary excretion of mercapturate and sulfate, metabolites derived from sulphydryls, were proportionally increased and excretion of unchanged drug was decreased by NAC. Absorption of acetaminophen from the small intestine was prevented by NAC and this was attributed to an inhibition in gastric emptying. Since all changes observed following NAC treatment could be attributed to inhibition of gastric emptying, it was considered the major mechanism responsible for affording in mice protection from acetaminophen-induced hepatocellular damage following concomitant oral administration.