gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

The role of hepatitis C virus RNA detection in various substrates of patients with chronic hepatitis C

Puncture biopsy of the liver and blood count were made in 72 patients with chronic hepatitis C (CHC). Morphological alterations in the liver were assessed by Knodell index. The blood serum, lymphocytes and hepatic tissue were examined for a genome form of hepatitis C virus (HCV) RNA, blood lymphocytes and hepatic tissue--for a relevant replication form. HCV RNA was detected using "nested" RT-PCR. Only 26% patients had symptoms of asthenovegetative and dyspeptic syndromes. Normal alaninaminotransferase (ALT) level was observed in 24% patients, the rest had it high. HCV RNA was encounted more frequently in hepatic tissue than lymphocytes or serum (83, 68 and 46%, respectively). A replication form of HCV RNA was present in hepatic tissue of 31% patients and was absent in the lymphocytes. The incidence of the RNA detection was not related either to the disease symptoms or morphological alterations in hepatic tissue. The occurrence of the genome and replication forms in hepatic tissue does not correlate to ALT level. HCV RNA occurs more often in the serum, blood lymphocytes and in three substrates simultaneously in patients with hyperalatemia.     

1-14C]Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.     

酒精性肝病患者血清TGF-β、IL-6和IL-8水平及临床意义

目的探讨酒精性肝病患者血清转化生长因子（transforming growth factor-β,TGF-β）白细胞介素-6（inter-leukin-6,IL-6）和白细胞介素-8（interleukin-8,IL-8）在酒精性肝病中的作用。方法 60例酒精性肝病患者按酒精性脂肪肝（n=20）、酒精性肝炎（n=20）和酒精性肝硬化（n=20）分为3组。采用ELISA法检测20例健康对照组和60例各类酒精性肝病患者血清中TGF-β、IL-6和IL-8水平。结果血清TGF-β、IL-6和IL-8水平随着肝脏病变程度加重而递增,酒精性脂肪肝组、酒精性肝炎组和酒精性肝硬化组3项指标水平均高于正常对照组,差异显著（P〈0.01）,其中以酒精性肝硬化组3项指标水平为最高。结论 TGF-β、IL-6和IL-8在酒精性肝病中具有重要作用,酒精性肝病患者血清TGF-β、IL-6和IL-8水平的检测可作为酒精性肝病病情监测和预后判断的有效指标。     

Hepatic damage in C282Y homozygotes relates to low numbers of CD8+ cells in the liver lobuli

BACKGROUND: Although most Caucasian patients with hereditary haemochromatosis (HH) show the same mutation in the HFE gene, the phenotypic expression of the disease varies greatly. We have previously shown that patients with HH who have high iron stores have low numbers of circulating CD8+ T lymphocytes. PATIENTS AND METHODS: Liver and peripheral blood were studied in 37 C282Y homozygous HH patients; nine normal livers and 11 livers from patients with cirrhosis due to hepatitis C virus or alcoholic liver disease were also investigated. Eleven jejunal biopsies from HH patients and 17 normal biopsies were studied. The numbers of CD8+ cells were determined in peripheral blood by fluorescence-activated cell sorting analysis, and in the liver or small intestine by immunohistochemistry. RESULTS: In HH patients the number of CD8+ T lymphocytes in peripheral blood correlated significantly with the number of CD8+ cells in the liver lobuli but not with that in the small intestine. Body iron stores correlated negatively with the number of CD8+ T lymphocytes in peripheral blood and in the liver, but not with the number in the small intestine. HH patients with cirrhosis had the lowest CD8+ cell count in liver sections, in contrast with other forms of cirrhosis. CONCLUSION: The results indicate that HH patients with the HFE C282Y mutation and low numbers of CD8+ cells in the liver lobuli have higher iron stores and are more prone to develop liver cirrhosis.     

Concanavalin A induced suppression of lymphocyte proliferation in chronic liver disease. A study of suppressor and responder populations in autologous and allogeneic systems

Abnormal T-cell regulation of lymphocyte proliferation may contribute towards tissue damaging mechanisms in chronic liver disease. We therefore studied Concanavalin A induced suppressor cell activity in T-T interaction in 47 patients with chronic liver disease, using both an autologous and an allogeneic system. In the autologous system, no differences were found between those with auto-immune chronic active hepatitis, HBsAg positive chronic active hepatitis, primary biliary cirrhosis, alcoholic liver disease and normal controls. However, several abnormalities were identified in allogeneic cultures with normal lymphocytes which allowed separate analysis of the influence of suppressor and responder cells from patients with chronic liver disease. An abnormality of the suppressor population was found in those with autoimmune chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease, while the responder population was abnormal in those with autoimmune or HBsAg positive CAH. Failure to demonstrate an abnormality in an autologous system may reflect a combined defect of suppressor and responder populations, and in this study the allogeneic system was a more sensitive index of abnormal cellular T-T interaction.     

Diagnostic significance of determining the blood content of lactic and uric acids in chronic liver lesions of alcoholic and viral etiologies

The concentration of lactic and uric acids in blood serum was measured in 115 patients with chronic liver lesions of virus (30 patients) and alcoholic (85 patients) etiology. The highest rise of lactic and uric acid concentrations was recorded in patients with alcoholic hepatitis and active alcoholic liver cirrhosis. The blood concentration of lactic and uric acids in alcoholic hepatopathy increased in parallel with an increment of the gravity of the pathological process, being the highest in patients with alcoholic hepatitis (lactic acid) and liver cirrhosis associated with the edematous ascites syndrome (uric acid). In inactive liver cirrhosis of alcoholic etiology, the concentrations of lactic and uric acids tended toward reduction, however, they were significantly higher than in the group of patients with virus liver lesions. Normal or negligible rises in the content of lactic and uric acids were seen in the groups of patients with chronic liver diseases of virus etiology. It is concluded that the measurement of the content of lactic and uric acids plays a diagnostic part in different patterns of alcoholic hepatopathies.     

原发性胆汁性肝硬化患者肝硬化期外周血淋巴细胞计数及T细胞亚群检测与分析

目的探讨原发性胆汁性肝硬化(PBC)患者肝硬化期外周血淋巴细胞总数及T细胞亚群的特点并分析影响因素及临床意义。方法对86例肝硬化期PBC患者的临床资料、实验诊断数据进行回顾性分析,比较40例代偿期和46例失代偿期PBC患者肝功、免疫学指标和外周血淋巴细胞亚群特点,对可能的影响因素进行相关性分析。结果失代偿期PBC患者年龄、血清总胆红素(TBil)水平、血清总IgA水平、Mayo评分高于代偿期患者(P0.05),而ALT、ALB、外周血淋巴细胞绝对数(LYMPH)、淋巴细胞百分率(LYMPH%)、T淋巴细胞绝对数(CD3+)、T辅助细胞绝对数(CD3+CD4+)和T抑制细胞绝对数(CD3+CD8+)均低于代偿期患者(P0.05);LYMPH、LYMPH%、CD3+、CD3+CD4+和CD3+CD8+结果中,失代偿期减低者频率均高于代偿期(45.7%vs.10%,34.8%vs.7.5%,58.7%vs.17.5%,45.7%vs.5%,60.9%vs.27.5%,P0.05),失代偿期增高者频率均低于代偿期(54.3%vs.90%,6.5%vs.27.5%,0 vs.20%,2.2%vs.22.5%,2.2%vs.10%,P0.05)。在可能的影响因素中,年龄、Mayo评分、上消化道出血、脾大或脾切除、腹水等肝硬化失代偿表现对结果影响呈负相关;而ALT、ALB对结果影响呈正相关。结论随着肝硬化程度的加深,PBC患者外周血淋巴细胞总数及T细胞亚群数量降低;从淋巴细胞定量角度分析,随着疾病的进展,PBC患者免疫水平下降。     

阿德福韦酯抗病毒治疗对慢性乙肝患者免疫功能的影响

目的探讨阿德福韦酯抗病毒治疗对慢性乙型肝炎患者外周血淋巴细胞各亚群的影响。方法对41例慢性乙型肝炎患者采用流式细胞术检测阿德福韦酯(ADV-dpv)治疗前、治疗12周和24周后与11例对照者外周血T淋巴细胞亚群进行比较,并结合血清丙氨酸氨基转移酶(ALT)和总胆红素(TbiL)水平及乙肝病毒DNA(HBV-DNA)载量水平进行统计学分析。结果治疗前各组患者外周血T淋巴细胞CD3+、CD4+、CD8+绝对计数值明显低于对照组,差异有统计学意义(P<0.05)。各组患者血清中ALT、TBiL水平及HBV-DNA载量水平与T淋巴细胞亚群失衡存在一致性,表现为慢性乙型肝炎(CHB)组和慢性重型肝炎(SH)组的ALT高于肝炎肝硬化(LC)组,差异有统计学意义(P<0.05),LC组和SH组患者外周血T淋巴细胞CD3+、CD4+、CD8+绝对计数值明显低于CHB组患者,差异有统计学意义(P<0.05)。ADV-dpv治疗12周和24周患者外周血T淋巴细胞CD3+、CD4+、CD8+绝对计数值明显高于治疗前,差异有统计学意义(P<0.05);各组患者ALT和TBiL水平及HBV-DNA载量较治疗前明显好转。结论慢性乙型肝炎在发展为重度和肝硬化的过程中外周血T淋巴细胞随病情的进展显著减少,经ADV-dpv抗病毒治疗后,肝功能明显改善,HBV-DNA复制明显减少,外周血淋巴细胞亚群绝对细胞数CD3+、CD4+、和CD8+进行性升高,T细胞亚群的状态呈逐渐改善的趋势。     

乙型病毒性肝炎肝硬化并肝脏畸胎瘤误诊为肝癌原因分析

目的提高乙型病毒性肝炎（乙肝）肝硬化并肝脏畸胎瘤诊断水平,减少误、漏诊。方法回顾分析1例乙肝肝硬化并肝脏畸胎瘤误诊为肝癌临床资料。结果患者以右上腹痛伴尿黄入院,经血清肝纤维化指标、肝炎病毒血清标志物检查诊断乙肝肝硬化,根据B超及CT检查显示肝右叶占位及甲胎蛋白（AFP）1320．00μg／L,诊断原发性肝癌。患者拒绝手术,经保肝、降酶及抗病毒治疗,肝功能及AFP改善,3个月后恢复正常。随访20个月,肝脏占位病变无变化,行手术治疗,经病理检查确诊肝脏畸胎瘤。结论乙肝肝硬化并肝脏占位伴AFP增高者,易误诊,条件许可情况下,应尽早手术确诊。     

Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoantibodies, sheep cell agglutinins and anti-albumin antibodies in alcoholic liver disease

The frequency of serum autoantibodies including anti-albumin antibodies was investigated for patients with various categories of alcoholic liver disease (ALD). The 95 patients were grouped into 3 categories: fatty liver (25 cases), alcoholic hepatitis (29 cases), and alcoholic cirrhosis (41 cases), and each group was matched with healthy controls by age, sex, ethnic origin and socio-economic status. For all patients with ALD, there was a 5-fold greater frequency over the controls of positive tests for antinuclear antibody (ANA), but titres were low; the pattern of ANA reactions was speckled in 50% of the cases. For patients with alcoholic cirrhosis, there was an 8-fold increase in frequency over the controls in anti-smooth muscle antibody (ASMA), but titres were low, pointing to a possibility that autoimmunity might be one of several determinants of progression of alcoholic hepatitis to cirrhosis. For none of the groups was there an increase over the controls in the mean titre of sheep red cell agglutinins, nor were there increased haemagglutinin titres of antibody to bovine serum albumin or to human albumin, arguing against a general increase in antibody production in ALD. Greater knowledge of the frequency, significance and pathogenicity of reactive autoantibodies which occur in response to various types of tissue damage is required for interpretation of the increase in ANA and ASMA in alcoholic liver disease.     

甲胎蛋白和癌胚抗原检测对良恶性肝病的诊断价值

目的探讨联合检测甲胎蛋白（AFP）和癌胚抗原（CEA）对原发性肝癌、转移性肝癌、肝硬化和病毒性肝炎的鉴别诊断价值。方法用时间分辨荧光免疫分析法检测220例各类肝病（76例原发性肝癌,25例转移性肝癌,37例肝硬化,82例病毒性肝炎）和50例健康对照者血清AFP和CEA。结果原发性肝癌组AFP极度增高,达（2984．6±4783．5）μg／L,肝硬化组AFP中度增高,为（121．6±223．5）μg／L,病毒性肝炎组和转移性肝癌组AFP均轻度增高,分别为（32．2±49．6）μg／L和（28．2±81．3）μg／L,以AFP〉500．0μg／L作为界值诊断原发性肝癌的灵敏度为76．3％,特异性达99。3%。CEA以转移性肝癌组最高,为（86。3±172．6）μg／L,明显比原发性肝癌、肝硬化、病毒性肝炎和健康对照组高,差异有统计学意义（P〈0．01）。结论联合检测AFP和CEA对原发性肝癌、转移性肝癌、肝硬化和病毒性肝炎有良好的鉴别诊断价值。     

Hepatic collagen proline hydroxylase activity in alcoholic liver disease.

The activity of hepatic collagen proline hydroxylase was examined in biopsy samples as a factor in collagen synthesis in 77 patients with alcoholic liver disease. The urinary excretion of peptide bound hydroxyproline was also measured in most of the patients, as an index of collagen degradation. The highest activities of collagen proline hydroxylase were found in the patients with alcoholic hepatitis. Enzyme activity was markedly increased in patients with non-specific changes on liver biopsy, whereas, patients with fatty infiltration had only mild elevations, and those with inactive cirrhosis had normal enzyme activity. Urinary hydroxyproline was elevated only in patients with alcoholic hepatitis and inactive cirrhosis. Follow-up determinations in 16 patients with alcoholic hepatitis, after 4 to 5 weeks, revealed a decrease in enzyme activity, but no change in urinary hydroxyproline. We conclude that among the types of alcohol-related liver diseases, alcoholic hepatitis is associated with the greatest turnover of hepatic collagen.     

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.     

Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of > 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus- related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.     

肝硬化患者肝脏R2值与血清铁蛋白含量的相关性研究

目的：应用磁共振多回波T2*扫描定量计算肝硬化患者肝脏R2*值,并与血清铁蛋白含量进行相关性分析。材料和方法：对32例健康人和42例临床诊断为乙型肝炎后肝硬化和酒精性肝硬化患者行磁共振多回波T2*序列扫描,并采集静脉血样本测量血清铁蛋白浓度。应用SPIN软件分别测量健康人和肝硬化患者肝脏右叶前段和右叶后段R2*值,取其平均值与血清铁蛋白浓度进行Pearson相关性分析。结果：32例健康人和42例肝硬化患者肝脏R2*值分别为（67.02±12.32） Hz和（85.30±28.48） Hz,经两独立样本t检验,显示二者有显著差异,t=3.335,P=0.001。42例肝硬化患者血清铁蛋白浓度为（165.5±104.4） ng/mL（均值±标准差）,R2*值与血清铁蛋白浓度的相关性分别为r=0.710,P=0.000。结论：肝硬化患者肝脏R2*值明显高于健康人,证明肝硬化患者肝脏铁浓度明显高于健康人。肝硬化患者肝脏R2*值与血清铁蛋白浓度有很好的相关性,证明R2*可以用于无创活体定量测量乙型肝炎后肝硬化和酒精性肝硬化患者肝脏内铁浓度。     

Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease

Abstract. Serum immunoreactive prolyl hydroxylase protein was measured in sixty-five patients with liver disease, and liver prolyl hydroxylase activity, immunoreactive prolyl hydroxylase protein and collagen hydroxyproline in forty of these patients. Serum immunoreactive prolyl hydroxylase protein was above the 95% confidence limit of the controls in most patients with primary biliary cirrhosis, portal cirrhosis, acute hepatitis and cancer with liver metastases, but below this in most patients with fatty liver, chronic active hepatitis, extrahepatic cholestasis, cholangitis, cancer without liver metastases and other malignant diseases. Elevated serum immunoreactive prolyl hydroxylase protein decreased rapidly with time in acute hepatitis but not in primary biliary cirrhosis. Liver prolyl hydroxylase activity and immunoreactive prolyl hydroxylase protein were elevated in the same diseases as serum immunoreactive prolyl hydroxylase protein, and correlated significantly with the latter whereas no correlation was found between serum immunoreactive prolyl hydroxylase protein and collagen hydroxyproline. Serum immunoreactive prolyl hydroxylase protein correlated highly significantly with serum alkaline phosphatase and weakly with serum aspartate aminotransferase in primary biliary cirrhosis, but not in any other disease. No correlation was found between serum immunoreactive prolyl hydroxylase protein and other tests of liver function. The results suggest that changes in serum immunoreactive prolyl hydroxylase protein in liver disease primarily reflect changes in this enzyme in the hepatic tissue, and that assays of serum immunoreactive prolyl hydroxylase in liver disease may give useful information on the actual hepatic collagen synthesis.     

肝病患者血清中3种标志物联合检测的意义

目的 探讨甲胎蛋白(AFP),癌胚抗原(CEA),恶性肿瘤相关物质(TSGF)定量联合检测在肝脏疾病诊断和治疗中的临床应用价值.方法 应用放射免疫分析测定肝病患者血清AFP和CEA含量,光电比色法测定TSGF的含量.结果 AFP在原发性肝病升高较为明显,阳性率可达86.6%;在慢性乙型肝炎及肝硬化患者中虽有不同程度的升高,但阳性率较低,分别为54.4%和40.0%.结论 对慢性乙型肝炎患者,肝硬化患者和原发性肝癌患者定时联合检测AFP、CEA、TSGF含量有助于了解肝病患者的病情变化、疗效观察以及病情监测和预后判断.