Chronic hepatitis C virus infection

Following acute hepatitis C virus infection (HCV), a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically due to the lymphotropism of HCV. Outstanding amongst these, due to their clear association with HCV, are mixed cryoglobulinaemia and the production of autoantibodies (autoAb). Other diseases such as non-Hodgkin lynphoma (NHL) or autoimmune thyroiditis do not have a clearly established association. Although the majority of patients with chronic hepatitis C have slight or moderately high levels and fluctuations of transaminases, as many as one third of those infected can show persistently normal levels of transaminases. The diagnosis of chronic HCV infection is based on serological tests, which detect the presence of antibodies against HCV, and on virological tests that detect RNA of the HCV, which confirm the existence of active infection. Finally, an important topic of chronic HCV infection, following diagnosis, is to ascertain the stage of fibrosis and the degree of inflammation, since both characteristics are very important for predicting the natural evolution and the need for treatment. Nowadays, this information can only be obtained through liver biopsy, which is recommended in patients with chronic HCV infection and high transaminases. Whether liver biopsy should be performed in patients with normal transaminases is still subject of controversy.     

Consider muscle disease in children with elevated transaminase

The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular injury but are highly concentrated in muscle cells. Consequently, muscular dystrophies such as Duchenne muscular dystrophy, lead to hypertransaminasemia. Elevation in ALT and AST is most striking during the early stages of disease, before onset of or when only subtle signs of muscle disease are present. Thus, the incidental finding of elevated ALT/AST may be the presenting sign of muscle disease in many children and provides an opportunity for early diagnosis. Many physicians, however, pursue extensive workup for liver disease in children who present with the incidental finding of elevated ALT/AST. This results in delayed diagnosis and initiation of treatment and increased expense and may lead to unnecessary invasive procedures. We report 12 patients with muscle disease who presented with a variety of symptoms and were found to have an incidental finding of elevated ALT/AST. We propose a rapid screening process for evaluating children with the incidental finding of elevated ALT/AST to shorten the time to diagnosis of muscle disease.     

部分生化指标对酒精性脂肪肝与非酒精性脂肪肝鉴别诊断意义的探讨

目的探讨部分生化指标对酒精性脂肪肝与非酒精性脂肪肝鉴别诊断的意义。方法对57例酒精性脂肪肝及226例非酒精性脂肪肝患者的血清甘油三酯、总胆固醇、尿酸、血糖、清蛋白、总蛋白、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、天门冬氨酸氨摹转移酶／丙氨酸氨基转移酶、谷氨酰转移酶等生化指标进行测定及分析。结果酒精性脂肪肝组的天门冬氨酸氨基转移酶、天门冬氨酸氨基转移酶／丙氨酸氨基转移酶、谷氨酰转移酶、尿酸异常的百分数分别为73．7％、35．1％、49．1％、59．6％,非酒精性脂肪肝组分别为28．8％、12．4％、16．4％、31．4％,两组相比差异有统计学意义。结论天门冬氨酸氨基转移酶、天门冬氨酸氨基转移酶／丙氨酸氨基转移酶、谷氨酰转移酶、尿酸、甘油三酯、总胆固醇等生化指标的检测对酒精性脂肪肝与非酒精性脂肪肝的鉴别诊断有意义。     

Serum dioxin and hepatic abnormalities in veterans of Operation Ranch Hand

PURPOSE: We studied hepatic abnormalities and indices of hepatic function in relation to exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. METHODS: The prevalence of ever having liver disease through March 1993, and level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase (GGT), lactic dehydrogenase (LDH), alkaline phosphatase, and total bilirubin were examined according to serum dioxin levels. RESULTS: We found an increased risk of "other liver disorders" among veterans with the highest dioxin levels [adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.2 to 2.1], due primarily to increased transaminases or LDH (adjusted OR = 2.7, 95% CI 1.4 to 5.1) and to other nonspecific liver abnormalities (adjusted OR = 1.4, 95% CI 1.0 to 2.0). CONCLUSIONS: Whether the associations observed were causal is unclear from these data.     

Management of asymptomatic elevated serum aminotransferase levels, particularly in nonalcoholic steatohepatitis]

At routine determination of serum activities of transaminases (aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased levels are frequently found. An algorithm may be used in the analysis of elevated transaminase levels: after elimination of the most frequent causes of hepatitis (alcoholic hepatitis, chronic hepatitis B and C) and some rare conditions (autoimmune hepatitis, alpha 1-antitrypsin deficiency, haemochromatosis and Wilson's disease), the diagnosis will often be nonalcoholic steatohepatitis. Although nonalcoholic steatohepatitis is considered a stable disease, recent literature shows a progression to cirrhosis in 8-17%. So far, no effective therapeutic strategies are available for nonalcoholic steatohepatitis.     

小儿轮状病毒性肠炎与血清转氨酶及心肌酶水平的相关性分析

目的:探讨小儿轮状病毒(RV)性肠炎与血清转氨酶和心肌酶谱变化的关系。方法:对2010～2011年收治的62例小儿RV性肠炎(观察组)和RV抗原阴性的57例肠炎患儿(对照组)进行血清转氨酶及心肌酶谱测定,对其结果进行对比分析。结果:观察组血清转氨酶明显高于对照组,且年龄越小肝功异常率越高;观察组患儿心肌酶谱各指标明显高于对照组,差异有统计学意义(P<0.05)。结论:小儿RV性肠炎可引起血清心肌酶谱和转氨酶异常;早期监测血清转氨酶和心肌酶谱变化,对小儿RV性肠炎的诊断和干预治疗有重要参考意义。     

Dietary restriction of energy and sugar results in a reduction in human cytochrome P450 2E1 activity

Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poorly investigated. Our aim was to assess the effect of dietary intake on in vivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-sugar diet. Liver function tests, liver volume, aminopyrine breath test (ABT) and chlorzoxazone (CZ) pharmacokinetics (area under the curve, AUC) which are known to reflect CYP2E1 activity were evaluated before and after 2 months restriction of dietary sugar intake. Features at inclusion were an increased BMI (30.3 (SD 3.2) kg/m2), high hepatic volume (1.96 (SD 0.48) litres), hyperechogenic liver parenchyma, elevated liver enzyme activities (alanine aminotransferase (EC 2.6.1.2) 58.6 (SD 17.4) IU/1 with alanine aminotransferase: aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together with a normal ABT value (0.68 (SD 0.21)% specific activity of administered dose of [14C]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20.3 (SD 7.1) micrograms/ml per h). A dietary sugar restriction was prescribed. On the basis of repeated interviews by the same dietitian, unaware of any clinical and biochemical data, six patients remained complaint to the diet and exhibited reductions in BMI (P < 0.001), serum alanine aminotransferase (P = 0.008), liver volume (P = 0.002) and CYP2E1 activity (P = 0.007), a significant increase in ABT (P < 0.001) together with the disappearance of liver hyperechogenicity at ultrasound. In contrast, the five non-compliant patients did not show any significant change in any of these variables. In conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, effective dietary sugar restriction is associated with a reduction in liver volume, a reduction in CYP2E1 activity and an increased aminopyrine metabolism rate.     

Test validity of periodic liver function tests in a population of Japanese male bank employees

The validity (sensitivity and specificity) of annual liver function tests, determined by assaying blood levels of aspartate aminotransferase, alanine aminotransferase and gammaglutamyl transpeptidase, was evaluated using the results of health checkups of male bank workers. The specificity of each liver function test to detect persons with fatty liver, excess alcohol users, and hepatic virus carriers, diagnosed respectively by ultrasound, detailed inquiry, and virus marker tests, was always higher than 80%, except for alanine aminotransferase in excess alcohol users (63.5%). However, the highest sensitivity to detect virus carriers was alanine aminotransferase to detect HCV antibody-positive workers, but it was only 45.5%. The highest sensitivity of the liver function tests to detect excess alcohol users in obese subjects was only 33.3%. The highest sensitivity by liver function tests to detect fatty liver was 35.7% which was inferior to that of the body mass index. These results indicate that the liver function tests mandated in the workplace periodic health checkups in Japan exhibit very low sensitivity for the detection of any of the proposed target clinical conditions.     

Combined Effect of <Emphasis Type="Italic">N</Emphasis>-Acetyl Cysteine,Zinc, and Selenium Against Chronic Dimethylmercury-Induced Oxidative Stress: A Biochemical and Histopathological Approach

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.     

Liver-protective action of silymarin therapy in chronic alcoholic liver diseases

The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.     

Role of liver function enzymes in diagnosis of choledocholithiasis in biliary colic patients

Liver functional tests due to inflammatory process which induced by cholecystitis might changed and some clinicians suggested that these changes might help us to stone prediction in common bile ducts and decrease hazards of performing ERCP and other invasive procedures. Present study was performed for assessment of role of liver functional test in diagnosis of common bile duct stone in patients with cholecystitis and help in their management. Present prospective study was performed between April 2010 and March 2011 on 350 patients who come to our hospital with cholecystitis or biliary colic diagnosis. Patients with cholesistitis diagnosis were underwent operation for removing gall bladder stone and retrograde cholangiopancreatography (ERCP) was performed for patients with suspicious to biliary colic and common bile duct (CBD) stones. Ultrasonography, aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP) and direct and total serum bilirubin were measured for all of participated patients. Mean of AST. ALT, ALP and total and direct bilirubin were had no significant differences between two study groups. In logistic regression analysis, after entering into the model only CBD diameter (OR: 20; P=0.00) and elevated serum level of ALT (OR: 2; P=0.04) were remained into the model and were known as independent predictor of cholelithiasis. Elevated level of liver enzymes had not main role in CBD diagnosis and ERCP had no to perform for suspicious CBD stone only with elevated liver enzyme and even with normal ultrasonography findings. Endosonography as non invasive procedure recommend for patients before ERCP.     

PA和BuChE在肝硬化Child-Pugh分级中的应用价值

目的　研究血清前白蛋白 (PA)和丁酰胆碱酯酶 (BuChE)的检测在肝硬化Child -Pugh分级中应用的价值。方法　测定 66例肝硬化患者和 5 0例健康人血清PA含量 ,BuChE活性及肝功能指标 (包括白蛋白 ,总胆红素 ,谷丙转氨酶 ) ,并按Child分级标准进行分组比较。结果　肝硬化组PA含量和BuChE活性较正常对照组显著降低 (P <0 0 1) ,按Child分级 ,肝硬化组A级PA含量与对照组之间差异不显著 (P >0 0 5 ) ,B级与A级 ,C级与B级之间差异显著 (P <0 0 1) ;BuChE活性A级与对照组 ,B级与A级 ,C级与B级之间均有显著性差异 (P <0 0 1) ,两项指标均随Child分级而明显降低。结论　血清PA含量和BuChE活性检测对判断肝硬化程度具有重要的指导意义 ,可作为肝硬化患者病情诊断和预后判断的指标。     

Relationship between fatty liver and coronary risk factors]

Fatty liver is a common finding in abdominal ultrasonographic examination in health check-ups, but the relationship between fatty liver and so-called coronary risk factors has rarely been investigated from the viewpoint of prevention of coronary heart disease. The purpose of the present study was to elucidate such a relationship by comparing the coronary risk factors with and without fatty liver by using data from health check-ups for the mid-management and management staff of a manufacturing company. The majority (77.1%) of those with fatty liver in the present study were categorized as "normal" or "marginally obese" and only a small portion (22.9%) were categorized as "obese" according to the classification of the body mass index. The group of subjects with fatty liver had significantly lower mean HDL-cholesterol and higher levels of fasting blood sugar, HDL/total cholesterol ratio, triglyceride, uric acid and transaminases, than those parameters in subjects without fatty liver, even after adjustment for age and body-mass index. The blood pressure (both systolic and diastolic) and total cholesterol level did not show any significant difference after controlling the covariates. Our results indicated that fatty liver has a close correlation with the majority of coronary risk factors causing atheroscleotic diseases, and most of these relationships are independent of total body mass. Our results regarding fatty liver are a help to occupational health personnel when advising workers to reduce their own risk of atherogeic diseases.     

Inhibitory effect of 6-azauracil on beta-alanine metabolism in rat

The effect of 6-azauracil on beta-alanine metabolism was investigated in vivo in the rat. Both of the enzymes beta-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase [R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are beta-alanine catabolizing enzymes from rat liver and kidney, were inactivated by 6-azauracil injection, while dihydrouracil dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase, which are pyrimidine metabolizing enzymes, were not affected. The content of beta-alanine was increased, but the level of uridine and uracil in rat liver was not affected, by 6-azauracil. When a crude enzyme preparation was passed through a Sephacryl S-200 column, both enzymes could be separated from each other. beta-Alanine-oxoglutarate aminotransferase and beta-alanine-pyruvate aminotransferase activities in rat liver decreased to 27.4% and 63.9%, respectively, upon 6-azauracil injection, and those in kidney were 11.7% and 38.3%, respectively. From these findings, it is suggested that the accumulation of beta-alanine in 6-azauracil-treated rat liver might be caused by the inhibition of beta-alanine catabolizing enzymes, but not by an increase in the uridine pool nor by the activation of pyrimidine metabolism.     

Statins and elevated liver tests: what's the fuss?

Order liver function tests before starting statin therapy, 12 weeks after initiation, with any dose increase, and periodically for long-term maintenance therapy. Mild elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (<3 times the upper limit of normal [ULN]) following statin therapy do not appear to lead to significant liver toxicity over time. Other medications that lower low-density lipoprotein (LDL), and might be substituted for statins, may not improve morbidity and mortality.     

FTL在慢性肝病患者血清中的表达及临床意义

目的 探讨血清铁蛋白轻链(Ferritin light chain, FTL)在慢性肝脏疾病进展过程中表达水平的变化及其潜在的临床应用价值。方法 利用iTRAQ定量蛋白组学技术对随机选取的慢性肝病患者与健康者血清进行比较研究, 酶联免疫吸附法（ELISA）检测显著性差异蛋白FTL在不同阶段慢性肝病患者和健康者血清中的含量, 应用统计学方法对FTL在不同阶段慢性肝病中表达量进行组间比较,并分析其与血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清铁蛋白(Serum Ferritin, SF)的相关性。结果 通过对慢性肝病患者与健康者血清样品进行质谱分析, 筛选并鉴定出差异表达蛋白69个,其中FTL是慢性肝病患者血清中表达明显上调的差异蛋白。ELISA检测不同阶段慢性肝病患者和健康者血清中的FTL表达水平,结果显示不同阶段慢性肝病患者血清中的FTL表达均高于健康者,且随着肝病病情进展呈下降趋势;统计学分析显示:FTL与ALT、AST、SF呈正相关性(P均＜0.01）。不同阶段慢性肝病患者血清中FTL表达差异均具有统计学意义(P＜0.01）,其表达水平和肝病进展程度呈负相关性(rs = -0.405,P ＜0.01)。结论 FTL与慢性肝脏疾病密切相关, 其表达水平不仅能体现肝脏的损伤状况,还能反映肝脏疾病的进展情况,在慢性肝病诊断、监测和治疗方面均具有良好的应用前景。     

决明子、枸杞果、绿茶对非酒精性脂肪肝小鼠血脂代谢的影响对比

目的 对比决明子、枸杞果、绿茶对非酒精性脂肪肝模型小鼠血脂代谢以及脂肪肝发展的影响情况.方法 采用高脂饮食法（high fat diet,HFD）建立非酒精性脂肪肝小鼠模型,用决明子、枸杞果、绿茶浓缩液分别对甲、乙、丙三组予以灌胃治疗,同时对丁组模型对照组和戊组空白对照组予等量的生理盐水灌胃.经过4周喂养后,每2周在各组分别取5只小鼠进行解剖,取肝脏做石蜡切片进行组织病理学观察.同时采集静脉血,采用全自动生化分析仪检测血清总胆固醇（TC）、甘油三酯（TG）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、低密度脂蛋白胆固醇（LDLC）以及高密度脂蛋白胆固醇（HDL-C）（n＝5）,并取肝脏,制肝匀浆,测定LTG、LTC.结果 模型治疗组与两对照组相比,HDL-C有所升高,差异有统计学意义（ P 〈0.05）,TC、TG、ALT、AST、LDL-C、LTG、LTC明显降低,差异有统计学意义（ P 〈0.01）.结论 决明子、枸杞果、绿茶对于非酒精性脂肪肝模型对肝脏脂肪沉积以及肝内炎症发展均有一定程度的抑制作用,其抑制强度分别为决明子〉枸杞果〉绿茶.     

Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women

Proteins (total, albumin, globulin and their subfractions), carbohydrate (intravenous glucose tolerance test), lipids (serum cholesterol, triglycerides and phospholipids), and liver function tests (alkaline phosphatase, lactic dehydrogenase and aspartate aminotransferase activities in the serum, bromsulphathalein retention test and serum bilirubin) were studied in 12 non-lactating healthy Thai subjects before, and subsequently at 3 weeks and 3, 6, 9 and 12 months after the initiation of treatment with injectable medroxyprogesterone acetate (150 mg I.M. every 90 days). Serum protein and lipid levels, and the results of liver function and I.V. glucose tolerance tests, remained unchanged in all subjects throughout the one-year study period. However, a significant and persistent increased insulin level was noted in all subjects, after initiation of the hormone treatment, during the first thirty minutes of intravenous glucose load. It is concluded that injectable medroxyprogesterone acetate used as a contraceptive agent does not interfere with glucose tolerance, lipid and protein metabolism, and that the liver function remains normal during its administration.     

Liver damage among shoe repairers.

BACKGROUND: The risk of hepatotoxicity in the shoe industry has already been suggested, however, there has been no investigation among the craftsmen who repair shoes. METHODS: A group of 33 shoe repairers who work in supermarkets, and who use the same glues which contain mixtures of potentially hepatotoxic solvents were identified. A control group of 61 workers not exposed to hepatotoxic substances was also examined. All participants completed a questionnaire designed to identify potential risk factors and the main non-occupational confounding factors for hepatotoxicity. Laboratory tests, commonly used in clinical practice, were done to check whether they were useful markers of hepatotoxicity due to exposure to solvent mixtures, and to investigate which tests should be used in the screening campaigns. RESULTS: The exposed workers had a higher prevalence of elevated mean alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated bilirubin (P=0.0001), and alkaline phosphatase (AP) (P=0.004) than controls did. The number of workers who had values outside the upper limit of normal for our laboratory was significantly higher (ALT P=0.034, AST P=0. 037, conjugated bilirubin P=0.014). Exposed workers all had a ratio of ALT to AST greater than 1, with a mean of 1.5; it was > 1.6 in more than half the exposed workers. CONCLUSIONS: The findings suggest that there is the possibility of liver involvement among even asymptomatic shoe repairers, and that periodic liver screening may be useful; furthermore, use of these tests (especially the ratio of ALT to AST) for craftsmen who repair shoes, and are exposed to solvent mixtures, is advisable even when environmental monitoring indicates levels below the threshold limit values (TLVs).     

Gilbert Syndrome in a Young Ethiopian Man: First Case Report

BackgroundGilbert syndrome is a well-recognized condition causing unconjugated hyperbilirubinemia with otherwise normal transaminases and liver function tests.CaseA 21 year old male patient presented with recurrent episodes of jaundice over four years. The episodes were preceded by stressful conditions and intercurrent illnesses. All laboratory prameters were normal except an unconjugated hyperbilirubinemia. A diagnosis of Gilbert syndrome was made after careful clinical evaluation.ConclusionRecognizing Gilbert syndrome has important clinical implicaitions by avoiding uncessary and expensive workup of patients with jaundice. Mangement entails avoiding stressful conditions and prolonged fasting.