黄曲霉毒素与肝细胞癌分子生物学研究

大量流行病学和实验研究表明，黄曲霉毒素B1（AFB；）与肝细胞癌（HCC）密切相关[1]，目前已进入分子水平研究。1AFB与白蛋白结合AFB1-白蛋白加合物是一种黄曲霉毒素暴露的长期生物标志物。AFB1-白蛋白加合物的半衰期为14～20天，与健康人白蛋白半衰期相似，提示AFB1-白蛋白加合物是稳定的，并可作为AFB1暴露超过周或月的靶向生物标志物[2]。启东是肝癌高发区，常见的病因是HBV和AFB；。为了研究病毒化学交互作用时间模式和可能性，wans等’‘］收集了启东大兴乡居民血清，应用高效液相色谱法，测定黄曲霉毒素分子标志物。在两…     

广西原发性肝细胞癌黄曲霉毒素B1-DNA加合物表达及p53第249密码子突变分析

目的 通过研究广西地区肝癌患者中黄曲霉毒素B1(Aflatoxin B1,AFB1)-DNA加合物的表达和p53第249密码子突变情况及其关系,探讨AFB1长期暴露与人群原发性肝细胞癌(hepatocellular carcinoma,HCC)发生的关系.方法 实验组为广西医科大学第一附属医院肝胆外科收治的63例HCC患者行根治性手术切除的肝肿瘤组织.按肿瘤大小分为小肝癌组(≤5cm)和大肝癌组(＞5cm),同时小肝癌组包括两个亚组Ⅰ组(≤3cm)和Ⅱ组(＞3cm).另取10例来自肝移植供肝及肝外伤切除的正常肝组织作为正常对照组.通过免疫组织化学(immunohistochemistry,IHC)法检测各组样本AFB1-DNA加合物的表达,并以PCR结合直接测序的方法 检测其p53第249密码子的突变情况.结果 小肝癌组的AFB1-DNA加合物阳性率最高(73.8%),显著高于大肝癌组(P=0.016).而小肝癌组p53第249密码子的突变率(35.7%)却显著低于大肝癌组(P=0.007).正常对照组AFB1-DNA加合物阳性率为50.0%,但未发现p53第249密码子存在突变.Ⅰ组与Ⅱ组之间无论是AFB1-DNA加合物阳性率还是p53第249密码子的突变率差异均无统计学意义(P1=0.676,P2=1.000).实验组中,33.3%的样本为AFB1-DNA加合物和p53第249密码子突变双阳性,22.2%的样本为AFB1-DNA加合物和第249密码子突变双阴性.结论 广西为AFB1高污染地区,正常人群普遍存在AFB1的暴露.AFB1的暴露可增加HCC的发病概率.p53第249密码子突变可能是影响AFB1相关HCC发生、发展的因素.结合AFB1-DNA加合物表达和第249密码子突变的情况,可有效地了解肝癌患者长期持续性或非持续性的AFB1暴露下DNA的累积损伤情况.     

广西原发性肝细胞癌黄曲霉毒素B_1-DNA加合物表达及p53第249密码子突变分析

目的通过研究广西地区肝癌患者中黄曲霉毒素B1（Aflatoxin B1,AFB1）-DNA加合物的表达和p53第249密码子突变情况及其关系,探讨AFB1长期暴露与人群原发性肝细胞癌（hepatocellular carcinoma,HCC）发生的关系。方法实验组为广西医科大学第一附属医院肝胆外科收治的63例HCC患者行根治性手术切除的肝肿瘤组织。按肿瘤大小分为小肝癌组（≤5cm）和大肝癌组（〉5cm）,同时小肝癌组包括两个亚组Ⅰ组（≤3cm）和Ⅱ组（〉3cm）。另取10例来自肝移植供肝及肝外伤切除的正常肝组织作为正常对照组。通过免疫组织化学（immunohistochemistry,IHC）法检测各组样本AFB1-DNA加合物的表达,并以PCR结合直接测序的方法检测其p53第249密码子的突变情况。结果小肝癌组的AFB1-DNA加合物阳性率最高（73.8%）,显著高于大肝癌组（P=0.016）。而小肝癌组p53第249密码子的突变率（35.7%）却显著低于大肝癌组（P=0.007）。正常对照组AFB1-DNA加合物阳性率为50.0%,但未发现p53第249密码子存在突变。Ⅰ组与Ⅱ组之间无论是AFB1-DNA加合物阳性率还是p53第249密码子的突变率差异均无统计学意义（P1=0.676,P2=1.000）。实验组中,33.3%的样本为AFB1-DNA加合物和p53第249密码子突变双阳性,22.2%的样本为AFB1-DNA加合物和第249密码子突变双阴性。结论广西为AFB1高污染地区,正常人群普遍存在AFB1的暴露。AFB1的暴露可增加HCC的发病概率。p53第249密码子突变可能是影响AFB1相关HCC发生、发展的因素。结合AFB1-DNA加合物表达和第249密码子突变的情况,可有效地了解肝癌患者长期持续性或非持续性的AFB1暴露下DNA的累积损伤情况。     

CEA、CYFRA21-1、CA125检测在肺癌诊断中的应用

[目的]探讨CEA、CYFRA21-1、CA125联合检测在肺癌诊断中的价值.[方法]采用电化学发光法检测肺部疾病患者血清中CEA、CYFRA21-1、CA125浓度水平.[结果]肺癌组血清CEA、CYFRA21-1、CA125水平均明显高于肺部良性病变组及正常对照组,经统计学分析差异显著.其中CEA、CA125以肺腺癌中最高,阳性率分别78.13％、65.63％;CYFRA21-1以肺鳞癌中最高,阳性率达51.9％.肿瘤患者单独检测以上肿瘤标志物阳性率较低(CEA28.00％,CYFRA21-1 36.80％,CA125 30.40％.而联合检测以上标志物阳性率则大大提高,肺癌的检测阳性率可达70.41％,肺鳞癌达64.56％,腺癌达87.50％,小细胞癌达63.64％.[结论]临床上适当选用多项血清肿瘤标志物联合检测有利于肺癌的早期诊断与鉴别诊断.     

甲胎蛋白异质体检测在肝癌诊断中的意义

[目的]探讨联合检测血清甲胎蛋白(AFP)及甲胎蛋白异质体(AFP-L3)含量在肝癌诊断中的意义.[方法]采用全自动化学发光分析技术检测185例肝癌患者、225例肝良性病变患者以及 200名健康对照中血清AFP和AFP-L3的含量。[结果]肝癌组、肝脏良性病变组AFP、AFP-L3值均高于正常对照组(P＜0.05),肝癌组AFP和AFP-L3水平均高于肝脏良性病变组(P＜0.05).AFP诊断肝癌的灵敏度为68.11％,特异性为80.94％;而AFP-L3灵敏度为83.78%,特异性为96.00％;AFP及AFP-L3联合检测的灵敏度为93.51%,特异性为78.35%。[结论]AFP、AFP-L3联合检测对肝癌早期诊断及鉴别诊断具有一定意义.     

广西原发性肝癌高危人群的茶多酚干预研究

目的:评估茶多酚对广西原发性肝癌高危人群在黄曲霉毒素暴露中的预防效果。方法:本研究采用随机双盲法进行为期1 年的茶多酚干预性试验,共有130 例经过筛选的实验对象,严格按照随机双盲法分为两组:茶多酚组和安慰剂组;各组分别服用茶多酚500mg/d 和相应的安慰剂;并在多个时间点采集血液样品,利用放射免疫法检测不同时间点两组实验对象血清中的黄曲霉毒素白蛋白加合物水平。结果:130 例实验对象的血清中均可检测到黄曲霉毒素白蛋白加合物。两组中茶多酚干预组实验对象血清的黄曲霉毒素白蛋白加合物水平呈下降趋势,并在服用茶多酚12个月后呈现显著性降低的情况（P<0.05）;而安慰剂组实验对象血清各时间点的黄曲霉毒素白蛋白加合物水平未出现显著性的改变（P>0.05）。 结论:茶多酚可以降低原发性肝癌高发人群黄曲霉毒素的暴露水平。      

肝癌患者淀粉酶糖链异常、证型差异及相关机制

目的：研究肝癌患者的血清淀粉酶糖链变化、中医证型差异及与自由基的相关性。方法：凝集素亲和沉淀法检测肝癌患者、肝硬化患者、肝炎患者血清淀粉酶的多种凝集素结合率；同时检测血清丙二醛（malindialdehyde，MDA）、血清淀粉酶活性，分析淀粉酶的各凝集素结合率与自由基的相关性，分析以上指标在不同证型肝癌患者间的差异。结果：肝癌患者血清淀粉酶的ConA、PSA、PNA、LCA结合率明显高于肝炎组及正常组；肝硬化组淀粉酶的ConA、PSA、PNA、LCA的结合率亦明显高于肝炎组及正常组，肝癌肝郁脾虚患者血清淀粉酶的PSA、LCA的结合率明显高于肝癌肝肾阴虚患者，肝癌肝郁脾虚患者血清淀粉酶的ConA结合率明显高于肝癌气滞血瘀患者；血清淀粉酶的PSA、PNA、LCA结合率与MDA水平呈显著正相关。结论：肝癌患者血清淀粉酶分子中核心岩藻糖基化的高甘露糖型、杂合型糖链增多，其糖链末端唾液酸基、岩藻糖基减少，致D-半乳糖的暴露增多，此外，肝癌患者血清淀粉酶糖链末端D-半乳糖基亦减少，致N-乙酰氨基葡萄糖基暴露增多，肝硬化患者血清淀粉酶糖链亦有以上变化，这可能与自由基损害糖链有关。肝癌肝郁脾虚患者血清淀粉酶分子中核心岩藻糖基化的高甘露糖型、杂合型糖链增多，其糖链末端的D-半乳糖基减少，致N-乙酰氨基葡萄糖基暴露增多；而肝癌气滞血瘀和肝癌肝肾阴虚患者血清淀粉酶糖链无此变化，表明肝郁脾虚在肝癌患者血清淀粉酶异常糖链的形成方面可能起重要作用。     

血清补体C3a检测在结肠癌诊断中的价值

目的 评价血清补体C3a检测对结肠癌诊断的价值.方法 用酶联免疫吸附法检测结肠癌、胃癌、肝癌以及结肠良性疾病患者和健康人的血清补体C3a水平.结果 结肠癌患者血清补体C3a水平是600±189 ng/ml,明显高于其它各组(P<0.05).结肠良性疾病患者,胃癌、肝癌组血清补体C3a水平与健康人比较无统计学差异(P>0.05).结论 血清补体C3a检测对结肠癌的诊断具有一定的价值,并且可能具有一定的特异性.     

子宫内膜癌患者血清TK1检测的临床意义

目的：探讨血清细胞质胸苷激酶1（TK1）检测在子宫内膜癌诊治中的临床价值。方法：利用免疫印迹增强化学发光法（ECLA）检测154例子宫内膜癌患者血清TK1的含量,同时检测130例子宫内膜良性疾病和121名健康人血清中的TK1含量。结果：子宫内膜癌患者TK1水平[3.14（1.87—3.95）pmol／L]显著高于子宫内膜良性疾病组[1.31（0.95—1.63）pmol／L]和正常对照组[1.24（0.62—1.49）pmol／L]（P〈0.01）;而子宫内膜良性疾病组和正常对照组之间差异无统计学意义（P〉0.05）。154例子宫内膜癌患者手术后血清TK1水平明显下降。子宫内膜癌患者血清TK1阳性率（61.7％）远高于其他生殖道肿瘤标志物[癌胚抗原（CEA）（15.6％）]、糖抗原[CA199（14.5％）,CA125（17.9％）]。结论：血清TK1检测在子宫内膜癌诊断、预后判断、疗效监测等方面具有一定的临床应用价值。     

EPHX代谢酶的遗传多态性和肝癌易感性的相关性研究

目的探讨环氧化物水解酶(EPHX)和谷胱甘肽转硫酶(GST)基因型及血清黄曲霉素B1(AFB1)加成物含量和肝癌易感性的相关性研究.方法以3对肝癌高发家族(62例)和相对应的非癌对照家族成员(58例)为研究对象,分别采用放射免疫法,PCR法测定所有成员血清中AFB1-白蛋白加成物量、HBsAg及血细胞的EPHX,GSTT1,GSTM1的基因型.结果1.高发家族成员有41.9%(26/62)血清AFB1-白蛋白加成物含量高于所有被测成员的中位值,而对照家族仅有15.5%(9/58)高于中位值,二组之间呈显著性差异(P＜0.001).2.在对照家族和高发家族AFB1-白蛋白含量低于中位值的人群中GSTM1,GSTT1,EPHX基因型的分布未见明显的差异;而AFB1-白蛋白含量高于中位值的高发家族人群,其EPHX 113编码位突变型百分率明显高于对照家族(P＜0.001),但GSTT1,GSTM1的基因型的分布无显著性差异.结论EPHX基因113编密子的突变与机体AFB暴露后形成的加成物的含量增加有关,从而可以推断与个体对黄曲霉素的敏感性和肝癌的易感性相关.     

原发性与转移性肝癌患者血清学检测的临床应用

  目的  探讨血清学检测指标在鉴别原发性与转移性肝癌时的临床应用价值。  方法  分别测定125例原发性肝癌患者组,135例转移性肝癌患者组及135例无肝转移的癌症患者组血清中ALT、AST、ALP、TBIL、DBIL、GGT、CHE、5'-NT、AFP、CEA、CA199的水平,采用方差析和Scheffe检验进行统计学分析。应用ROC曲线分析AFP、CEA和CA199对原发性肝癌及转移性肝癌的诊断价值。  结果  1）原发性肝癌组与转移性肝癌组之间血清AST、ALP、GGT、5'-NT、AFP及CEA水平差异有统计学意义（P < 0.05）。2）根据原发性肝癌组和转移性肝癌组AFP、CEA和CA199的ROC曲线下面积（Area under the ROC curve,AUC）判断,AFP对原发性肝癌诊断有一定的准确性,CEA、CA199对鉴别原发性肝癌与转移性肝癌有一定诊断价值。  结论  检测血清AST、GGT、5'-NT、AFP、CEA、CA199水平可对恶性肿瘤是否发生肝转移进行初步诊断,亦可对原发性肝癌与转移性肝癌的鉴别诊断提供佐证。      

全反式维甲酸联合三氧化二砷双药诱导缓解治疗对初治急性早幼粒细胞白血病患者肝功能的影响

目的探讨全反式维甲酸（ATRA）联合三氧化二砷（ATO）诱导缓解治疗急性早幼粒细胞白血病（APL）期间患者肝功能的变化。方法回顾性分析80例初治APL患者临床资料,其中38例经ATRA联合ATO双药诱导,42例经ATRA或ATO单药诱导,比较两组疗效及肝损害的差异。结果双药诱导组和单药诱导组完全缓解（CR）率差异无统计学意义[94．7％（36／38）比90．5％（38／42）,P〉0．05];双药诱导组CR时间短于单药诱导组[27d（20～36d）比35d（25～49d）,P〈0．05]。双药诱导组肝功能异常的发生率高于单药诱导组[68．4％（26／38）比42．9％（18／42）,P〈0．05];中＋重度肝功能异常的发生率高于单药诱导组[39．5％（15／38）比9．5％（4／42）,P〈0．05]。双药诱导组丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）异常率以及异常AIJT和AST检测峰值均高于单药诱导组（P〈0．05）;两组开始出现肝功能异常的时间以及血清总胆红素、碱性磷酸酶、1．谷氨酰转肽酶异常率的差异无统计学意义（P〉0．05）。结论ATRA联合ATO双药诱导缓解治疗APL加重了肝脏毒性,治疗的同时需密切监测肝功能,及时行保肝治疗。     

Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is associated with an increased risk of hepatocellular carcinoma (HCC). The hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular DNA. To determine whether nutritional factors and hormonal status may influence the binding of AFB1 to hepatic DNA, a cross- sectional study was performed on a total of 42 male asymptomatic hepatitis B surface antigen (HBsAg) carriers and 43 male non-carriers in a cohort study on the multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo, AFB1-N7-guanine, was measured by high- performance liquid chromatography in urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg carriers had a higher detection rate of urinary AFB1-DNA adducts than non-carriers and the difference was statistically significant after multivariate adjustment. After taking into account the total AFB1 urinary metabolite level, chronic HBsAg carrier status, and other potential confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and beta-carotene were positively associated with the detection rate of the AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level was inversely related to the presence of the adducts in urine. The association of urinary AFB1-DNA adducts with the plasma levels of cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was observed at both low and high exposure levels of AFB1. There was a synergistic interaction of plasma alpha-tocopherol with alpha- and beta- carotene on the adduct levels. No association with the adducts was found for plasma levels of retinol and testosterone. This study demonstrated different associations of antioxidant vitamins with AFB1- DNA adduct formation. The data consistent with our previous finding in cultured woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced AFB1-DNA adduct formation suggest that prospective investigation of the relationship between plasma micronutrients and risk of AFB1-related HCC is warranted.      

Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats.

The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.     

术前减黄对恶性低位胆道梗阻患者行胰十二指肠切除术前后肝功能变化的影响

背景与目的:胰十二指肠切除术后的合并症发生率仍然较高。术前胆道引流可以改善肝功能,但对于恶性低位胆道梗阻患者行胰十二指肠切除术术前肝功能的具体影响,以及肝功能指标在手术前后的变化情况,目前仍未见报道。本研究分析术前胆道引流对恶性低位胆道梗阻行胰十二指肠切除术患者术前肝功能的影响,以及肝功能指标在手术前后的变化及分析其预后。方法:收集98例行胰十二指肠切除术恶性低位胆道梗阻患者[总胆红素(totalbilirubin,TB)>85μmol/L]的临床资料,分析肝功能指标和胆红素之间的相关性、手术前后肝功能的变化、以及分析预后;按照术前是否胆道引流分为减黄组、未减黄组,分析术前胆道引流对肝功能指标的影响,按照术后是否发生并发症分为有、无并发症组,分析并发症对术后肝功能变化的影响。结果:γ-谷氨酰转移酶(γ-glutamyltransferase,GGT)与TB呈正相关关系(r=0.368,P<0.001),而碱性磷酸酶(alkaline phosphatase,ALP)与TB无相关性。减黄组术前胆道引流后,TB、直接胆红素(direct bilirubin,DB)、丙氨酸转氨酶(alanine aminotransferase,ALT)、ALP、GGT分别由术前的(266±119)μmol/L,(160±75)μmol/L,(161±88)U/L,(508±276)U/L,(537±417)U/L减至术后的(184±115)μmol/L,(112±67)μmol/L,(99±90)U/L,(319±145)U/L,(203±176)U/L,差异有统计学意义(P<0.05),但减黄前后天冬氨酸转氨酶(aspartate aminotransferase,AST)的变化不显著。全组患者ALT、AST、GGT、ALP术后第7天达最低值,第14天轻度上升;术后7d时,TB、DB在有并发症组为(152±68)μmol/L,(80±57)μmol/L,较无并发症组的(101±77)μmol/L,(58±45)μmol/L升高,两组差异有统计学意义(P<0.05),白蛋白(albumin,ALB)在有、无并发症组分别为(36.2±4.7)g/L,(38.6±5.2)g/L,两组差异有统计学意义(P<0.05)。减黄组中位生存期19.2个月,未减黄组中位生存期16.4个月,两组相比差异无统计学意义(P=0.458)。结论:GGT更能反映恶性低位胆道梗阻的程度。术前胆道引流可以有效的改善肝功能,并发症的出现影响恶性低位胆道梗阻行胰十二指肠切除术患者术后短期内的黄疸以及肝功能的改善。术前减黄对远期预后无影响。     

In vivo formation of aflatoxin B1-DNA adducts in parenchymal and non-parenchymal cells of rat liver.

The induction of hepatocellular carcinoma from liver parenchymal cells in laboratory animals by aflatoxin B1 (AFB1) is well documented. In contrast no tumours arising from the sinusoidal cell population have been reported after exposure to AFB1. The apparent resistance of the latter cell type was investigated at the level of DNA adduct formation in vivo in male Sprague-Dawley rats. Liver parenchymal and non-parenchymal cell populations were isolated from rats at 20 min and 1, 24 and 72 h after administration of 240 microCi (0.6 mg) [G-3H]AFB1/kg. AFB1-DNA binding was observed in both liver cell subpopulations and was 3- to 5-fold higher in parenchymal cells than in non-parenchymal cells. The major DNA adduct found in parenchymal cells at 1 h after AFB1 administration was 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-gua), whereas at later time points the persistent secondary adduct, AFB1-formamidopyrimidine, predominated. In contrast, AFB1-gua was not observed at any time in DNA from non-parenchymal cells and the secondary adducts predominated throughout. These observations are discussed with reference to the susceptibility of different liver cell types to AFB1-carcinogenesis and the possible roles of the major AFB1-DNA adduct species.     

Changes in biochemical laboratory investigation in patients treated with constant infusion recombinant interleukin-2.

Eight patients with metastatic hypernephroma were treated with constant infusion recombinant Interleukin-2 (rIL-2), changes in renal and hepatic function and protein levels were monitored during 2 cycles of treatment. The rIL-2 infusion caused a reversible fall in ures and a non-reversible rise in creatinine. Liver function tests (bilirubin, ALT, ALP and GGT) rose during rIL-2 treatment and had returned to pretreatment levels 3 weeks after the last day of rIL-2. There was also a reversible fall in serum protein levels during rIL-2 infusion. Although constant infusion rIL-2 ameliorated much of the severe toxicities usually seen with high-dose bolus rIL-2, the non-reversible rise in serum creatinine levels is not a previously reported feature of rIL-2 therapy.     

Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet

Nutritional modulation of male Fischer rats by a choline-deficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1). The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline-deficient/methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 micrograms [3H]AFB1 for 5 days a week over 2 weeks. Six choline-deficient and four control diet rats were killed 2 h after each dose, and liver DNA isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H]AFB1 administration. At all time points HPLC analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation between the dietary groups were observed following the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the choline-deficient animals were significantly increased during the multiple dose schedule. When total aflatoxin-DNA adduct levels were integrated over the 10 day dose period, a 41% increase in adduct burden was determined for the choline-deficient animals. While this increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, the biochemical basis for this effect still needs to be elucidated.     

Frequency of OBI among Patients with Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is recognized as a serious disease in which the body’s immune system attacks liver cells so untreated patients may consequently suffer from liver cirrhosis, hepatocellular carcinoma (HCC) and liver failure. The role of viral infection may be involved in AIH. Presence of anti-HBc alone is a predictive signal of potential OBI. Thus, this study was conducted to evaluate the rate OBI among the patients with AIH. Methods: The sera of 20 consecutive  patients with AIH were collected and tested for LFT (ALT, AST, ALP elevation), Immunoglobulin (IgG) level, bilirubin, anti -LKM-1, ASMA, ANA in titer, HBsAg, HBcIgG. The patients’ sera were also tested for HBV DNA by nested PCR and Real-time PCR. Results: Out of 20 patients, 10 (50%) were males and 10 (50%) females. The patients’ ages ranged from 25 to 71 years with the mean age of 44.5±13.4. All patients’ had elevated abnormal ALT and AST but their level of alkaline phosphatase was normal among the patients. All patients had IgG level>1.5 times upper than the normal limit. The patients’ sera were negative for HBsAg and HBV DNA (by nested PCR and real- time PCR). Only 2 (10%) females with AHI type 1 (positive  ANA, ASMA in titers >1:100 were positive for HBcIgG while no OBI detection was found among the males (p=0.005)). All diagnosis of the AHI was confirmed by pathologist. The level of ALT, AST among the cases with positive and negative OBI were (p=0.000) and (p=0.003), respectively. Conclusion: In the present study, two OBI female patients with type 1 AIH were positive for anti-HBc but negative for HBsAg and HBV DNA. With regard to the consequences of OBI, prior to prophylactic treatment, it is recommended to screen HBV markers including anti-HBc in all diagnosed patients with AIH.     

Epirubicin in hepatocellular carcinoma: pharmacokinetics and clinical activity

The pharmacokinetics and clinical activity of epirubicin were investigated in 16 patients with hepatocellular carcinoma (HCC) who received epirubicin at 75 mg/m²; the drug was given intravenously to 7 patients and via the hepatic artery to 9 patients (7 of whom also underwent embolisation). Lignocaine (1 mg/kg) was also given intravenously to 15 patients, and the metabolite monoethylglycinexylidide (MEGX) was measured as an indicator of liver function. Epirubicin clearance correlated with serum aspartate aminotransferase (AST), albumin and bilirubin values in patients treated intravenously or intraarterially. Although the route of administration did not affect the median total plasma clearance of epirubicin, early- and intermediate-phase clearance was higher following intraarterial administration. MEGX levels correlated with serum bilirubin levels but there was no correlation with albumin or AST values or epirubicin clearance. The rate of response to epirubicin was 3/13 (23%; 95% confidence interval, 8%–50%). Intravenous epirubicin was tolerated well, but intraarterial treatment was associated with significant morbidity. These data confirm that although current recommended dose adjustments are based primarily on serum bilirubin levels, altered epirubicin pharmacokinetics correlate more strongly with AST and albumin values than with serum bilirubin concentrations. However, at this dose and schedule, epirubicin has only modest activity against HCC.The work of N.A.D. and J.D.W. was supported in part by a grant from Farmitalia Carlo Erba