血清PAB,AAG,AAT的检测在肝脏疾病中的意义

目的探讨前白蛋白（PAB）、a1;-酸性糖蛋白（AAG）、a1-抗胰蛋白酶（AAT）在肝脏疾病中的临床意义。方法以散射比浊法测定132例各种类型肝脏疾病病人血清中的PAB、AAG.AAT值。结果PAB在急性肝炎（AH）、慢性肝炎（CH）、肝硬化（LC）.重症肝炎（FVH）、肝癌（HCC）中的测定结果分别为：14．77．8,12．25．4,8．63.8,5．84．3,9．24.2(mg／dl),明显低于对照组（P＜0．01）AAG在AH、CH.LC.FVH、HCC测定值分别为80．226．2,42.020．0,41．023．2,25．813．6,102．048．0(ml／d10),其中AH组和HCC组明显高于对照组（P＜0．01）,FVH组明显低于对照组（P＜0．01）;AAT在AH、CH、LC、FVH、HCC测定值分别为18339,17843,15162,15252,22672(ml/dl),其中HCC组明显高于对照组（P＜0．01）。结论PAN是反应早期肝脏功能损害的灵敏指标。PAB、AAG、AAT的检测对肝脏疾病的临床诊断有价值。     

肝病患者外周血血小板衍生生长因子-BB及其mRNA的表达

目的探讨肝病患者血小板衍生生长因子-BB(PDGF-BB)的表达水平及其意义。方法用ELISA检测30例慢性肝炎患者(26例乙型肝炎,4例丙型肝炎),24例肝炎后肝硬化患者、30例原发性肝癌患者和20名健康对照者血清PDGF-BB水平,用半定量RT-PCR技术检测外周血单个核细胞(PBMC)PDGF-B mRNA水平。结果各组肝病患者血清PDGF-BB及PBMC的PDGF-B mRNA水平与对照组比较差异有统计学意义(F=1774.40、1037.42,P<0.01),且与肝功能指标密切相关。结论PDGF-BB可能促进肝脏的炎性损害,导致严重的肝细胞损伤,检测血清PDGF-BB及PBMC中PDGF-B mRNA水平可能有助于了解肝病患者的肝损害程度。     

GB virus C in patients with liver disease of unknown etiology

To assess the prevalence of GBV-C in patients suffering unknown liver disease we have investigated the GBV-C-RNA in serum of 54 patients: 10 with acute and 32 with chronic non-A-E hepatitis (16 active and 16 persistent), 10 with hepatocellular carcinoma, 2 diagnosed with hepatic fulminant failure, and 91 healthy blood donors (control). PCR with primers from NS3 helicase region was performed and the product was identified by a double strand DNA enzyme immunoassay. GBV appears to infect 40 and 31% of acute or chronic non-A-E hepatitis respectively. Also the GBV genome was found in 1 in 10 samples of hepatocarcinoma, in 2 cases of fulminant hepatitis, and in 1 in 91 of the control group. In spite of these results the role of GBV in the etiology of liver diseases has to be analyzed in more comprehensive studies.     

Detection of serum and intrahepatic human hepatocyte growth factor in patients with type C liver diseases

We determined hepatocyte growth factor (HGF) levels in the serum and liver of patients with hepatitis C and assessed the relationship to histological findings of the liver and hepatitis C virus-related markers in the serum in patients with type C liver diseases. The subjects were 108 patients with chronic hepatitis C (CH), 70 patients with liver cirrhosis C (LC), 38 patients with hepatocellular carcinoma (HCC) and 20 patients with acute hepatitis (AH). As normal controls 20 subjects were studied. The serum HGF levels were measured using an enzyme-linked immunosorbent assay kit. Intrahepatic HGF was investigated by immunoperoxidase staining using monoclonal HGF antibody. The serum HGF level was highest in patients with AH. The serum HGF levels tended to be higher in patients with LC and HCC than those with CH. Further, the serum HGF level was related to the degree of intrahepatic inflammatory cell infiltration and fibrosis, and intrahepatic HGF was noted primarily in the cell membrane of mesenchymal cells in focal necrosis. The degree of intrahepatic HGF expression tended to be higher in patients with high serum HGF levels. In patients with HCC, however, HGF showed little localization in cancer cells, but was noted in infiltrating mesenchymal cells in both cancerous and noncancerous regions. In conclusion, the measurement of serum HGF levels may be useful for estimating the degree of intrahepatic inflammatory reaction and fibrosis. Although further study is necessary, the high serum level of HGF revealed high carcinogenic states in chronic hepatitis and liver cirrhosis type C.     

Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis.

Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.     

Pathogenic significance and organic virus levels in patients infected with TT virus.

Previous reports documented the recovery of a DNA virus from a patient with posttransfusion non-A-G hepatitis and named TT virus (TTV). Although the virus was initially detected as a causative agent of hepatitis, there is doubt about its pathogenicity. The aim of this study was to clarify the relationship between TTV and liver diseases. Histopathological examination of liver biopsies from 14 patients with TTV genotype 1 positive non-B, non-C and non-G chronic hepatitis showed mild fibrosis and periportal/piecemeal necrosis. Using the real-time detection (RTD)-PCR method, we found that TTV DNA levels of genotype 1 in liver samples from 3 such patients were 100- to 1,000-fold higher than those in the paired serum samples. Further investigation using various tissues from 2 autopsies of patients with hepatitis C with hepatocellular carcinoma revealed that the concentrations of TTV DNA in the liver were also higher than in serum samples. However, the highest TTV DNA concentrations in these 2 autopsies were found in the lung and bone marrow, respectively. Our results suggest that TTV may replicate in various tissues including the liver and may cause only mild liver damage.     

143例丙型肝炎患者血清透明质酸水平变化

目的测定丙型肝炎患者血清透明质酸浓度,探讨丙型肝炎患者血清透明质酸水平变化与患者肝功能损害程度的关系。方法收集丙型肝炎病毒（HCV）感染者143例,分成HCV携带者、轻度慢性丙型肝炎患者和中度慢性丙型肝炎患者3组。通过酶联免疫吸附试验（ELISA）测定患者血清透明质酸的水平。结果HCV携带者、轻度慢性丙型肝炎患者和中度慢性丙型肝炎患者血清透明质酸浓度均值分别为（38．3±7．4）、（48．9±5．9）、（67．2±9．9）ng／mL,均高于健康对照组均值（28．9±5．6）ng／mL,差异有统计学意义（P〈0．01）,血清透明质酸的水平随患者肝功能损害程度加重而增加。结论血清透明质酸升高是肝纤维化的特征之一,丙型肝炎患者血清透明质酸的水平随患者肝功能损害程度加重而增加,也预示随肝功能损害程度加重患者出现肝纤维化的概率增加。     

Clinical significance of serum 7S collagen in various liver diseases

Serum type IV collagen fragment (7S collagen domain) was measured in 30 controls and 152 liver disease patients with a radioimmunoassay using a polyclonal antibody to human placenta 7S collagen. The serum concentrations of 7S collagen (mean +/- SD) were 4.2 +/- 0.9 ng/mL in controls, 5.1 +/- 2.0 ng/mL in acute hepatitis, 6.5 +/- 2.5 ng/mL in chronic inactive hepatitis, 9.5 +/- 3.8 ng/mL in chronic active hepatitis, 14.4 +/- 7.5 ng/mL in liver cirrhosis, and 14.4 +/- 6.9 ng/mL in hepatocellular carcinoma. In acute hepatitis, 7S collagen was slightly increased, whereas type III procollagen N-peptide and prolyl hydroxylase were markedly increased. In chronic liver disease, 7S collagen concentrations increased with the severity of the disease, and also reflected the degree of fibrosis. The serum 7S collagen concentrations were significantly correlated with those of type III procollagen N-peptide and prolyl hydroxylase in all subjects. These results suggest that serum 7S collagen concentration is a useful diagnostic aid for determining hepatic collagen metabolism in liver diseases.     

Epstein Barr virus hepatitis: case series and review

Epstein Barr virus (EBV) infection causes asymptomatic liver-associated enzyme abnormalities in 80 to 90% of cases which are often unrecognized. Patients with acute EBV infections may also develop cholestatic hepatitis with associated jaundice and hepatitis with moderate elevations in the transaminase levels. Other gastrointestinal complications associated with EBV may include splenic rupture, liver failure due to acute and/or chronic EBV infection, and perhaps, autoimmune hepatitis and hepatocellular carcinoma. This article presents a case series of EBV infections with clinically significant hepatitis and reviews the literature on the gastrointestinal complications of EBV.     

Orcein-positive material in hepatocytes in viral hepatitis and other liver diseases

Summary Liver biopsy samples from 110 patients with various liver diseases were stained by orcein according to the method of Shikata et al. Orcein-positive hepatocellular material was observed in only the 31.7% of HBsAg seroposirive cases. A positive orcein reaction was frequently found in prottracted and chronic viral hepatitis and occasionally in other liver diseases, such as alcoholie and cholestatic hepatitis, as well as in cryptogenetic cirrhosis and in liver metastases. The results obtained suggest a more cautious evaluation of the diagnostic and prognostic significance of orcein positive hepatocellular material.     

The current endeavors to understand the pathogenesis of intractable liver diseases

The death due to liver diseases accounts for more the 35,000 cases every year in Japan for decades. Among these liver diseases, the Ministry of Health, Labor, and Welfare of Japan has named both fulminant hepatitis and primary biliary cirrhosis (PBC) as intractable liver diseases, since the precise mechanism of these diseases are unclear. Accordingly, there are no effective medical treatments other than liver transplantation toward these diseases. However, still the number of the liver transplantation performed in Japan is small. Thus, we have focused on the pathogenesis of these two intractable conditions. The fulminant hepatitis is a distinct form of acute hepatitis, and hepatitis B virus infection accounts for 20~30% of this lethal condition. Only tiny proportions of patients with acute HBV infection develop fulminant hepatitis (less than 10%). It has been widely believed both viral and host factors contribute for fulminant hepatitis, although still unknown factors are expected to be involved. On the other hand, PBC is a chronic progressive cholestatic liver disease. Clinical features of PBC include female predominance (80 to 90%), the presence of antimitochondrial antibody (up to 95%), and elevated serum levels of immunoglobulin M. Eventually, patients with PBC will develop liver failure due to biliary cirrhosis in spite of medical interventions. Immune-mediated processes are believed to be responsible for the pathogenesis, although the precise mechanism is yet to be determined. In this review article, our endeavors to understand the mechanism of these intractable liver diseases are discussed.     

绒毛与胚胎核型不一致性研究

为探讨绒毛与胚胎不一致问题，对２３例孕早期产前诊断与同一胚胎的羊水、脐带血、或人工流产绒毛对照及２７份人工流产绒毛与同一胚胎组织对照，提出了绒毛产前诊断结果的处理意见     

Clinical usefulness of serum tissue inhibitor of metalloproteinases (TIMP)-2 assay in patients with chronic liver disease in comparison with serum TIMP-1

Tissue inhibitors of metalloproteinases (TIMPs) are involved in liver fibrosis through impaired matrix degradation. Previous studies showed that the serum level of TIMP-1 was increased in patients with chronic liver disease, reflecting the liver TIMP-1 level, and that it is useful for assessing liver fibrosis. An enzyme immunoassay for TIMP-2 is now available. In this study, we examined the clinical usefulness of this serum TIMP-2 test for liver fibrosis in patients with chronic liver disease, in comparison with the serum TIMP-1 test. The serum TIMP-2 concentration was 61 +/- 13 ng/ml in healthy controls (n = 32), and 18% higher in the group of chronic active hepatitis (CAH) patients (n = 34), 64% higher in the liver cirrhosis (LC) group (n = 33) and 44% higher in the hepatocellular carcinoma (HCC) group (n = 61), and similar to the control level in the chronic persistent hepatitis (CPH) group (n = 23). In contrast, the serum TIMP-1 concentration was 155 +/- 17 ng/ml in the healthy controls, 18% higher in CPH, 35% in CAH, 63% higher in LC and 92% higher in HCC. The serum TIMP-2 level was related to the histological degrees of both periportal necrosis and liver fibrosis, as well as to the serum TIMP-1 level. However, the relationships for TIMP-2 were weaker compared to those of serum TIMP-1. These results suggest that compared to the serum TIMP-1 level, changes in the serum TIMP-2 level in chronic liver disease are less liver-specific, and the serum TIMP-2 level is less useful in the assessment of liver fibrosis in chronic liver disease.     

Clinical usefulness of malate dehydrogenase and its mitochondrial isoenzyme in comparison with aspartate aminotransferase and its mitochondrial isoenzyme in sera of patients with liver disease

The activities of serum malate dehydrogenase (MDH) and its mitochondrial isoenzyme (MDHm) were studied in sera of patients with liver disease. They proved to be more useful than those of aspartate aminotransferase (AST) and its mitochondrial isoenzyme for detection of hepatocellular carcinoma and acute circulatory failure, and for estimation of the severity of acute hepatitis. The N/T value measuring system, which is adaptable for autoanalysis and allows simultaneous determination of activities depending on NAD and thionicotinamide adenine dinucleotide (thio-NAD), yields both the total activity of MDH and the N/T value which was correlated significantly with MDHm/MDH (r = 0.748). Assay of MDH and its mitochondrial isoenzyme in association with the N/T value measuring system seems to be more useful and less time consuming for estimation of the severity of liver diseases than that of AST and its mitochondrial isoenzyme.     

检测腺苷脱氨酶和胆碱酯酶在肝病中的价值

目的 探讨血清腺苷脱氨酶(ADA)和胆碱酯酶(CHE)在肝病中的临床价值.方法 采用日立7020生化分析仪分别测定急性肝炎、慢性肝炎、肝硬化、肝癌疫患者及正常对照组血清ADA和CHE的活性,以在本院感染科住院的肝脏患者共146例为实验组,对照组84例.结果 血清ADA实验组均高于对照组(P＜0.01);而血清CHE则实验组低于对照组(P＜0.01);肝硬化时,ADA有近90%的病例明显上升.血清CHE除慢性肝炎外,其他各类肝病的阳性率都在90%左右.结论 联合检测血清ADA和CHE有助于肝病诊断和疗效观察以及预后的判断.     

Interleukin 1 alpha production by peripheral blood monocytes from patients with chronic liver disease and effect of sera on interleukin 1 alpha production

We investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.     

Biopsy-confirmed fenofibrate-induced severe jaundice: A case report

BACKGROUNDDrug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. DILI is mainly caused by painkillers and fever reducers, and it is often characterized by the type of hepatic injury (hepatocellular or cholestatic). This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease. We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARYA 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test. Abdominal ultrasound and computed tomography showed no biliary obstruction or non-specific findings in the liver. Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis. Following the biopsy, steroid therapy was initiated and after 3 wk of treatment, the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSIONIn patients with hyperlipidemia, treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis, warranting clinical attention.     

病毒性肝炎患者血清胆碱酯酶、凝血酶原活动度检测的临床意义

目的　研究血清胆碱酯酶 (CHE)、凝血酶原活动度 (PTA)与病毒性肝炎临床分型、病情及预后之间的关系。方法　分别采用酶速率法和比浊法测定 16 0例急性病毒性肝炎、慢性病毒性肝炎 (轻度、中度、重度 )、肝炎肝硬化患者血CHE和PTA ,其中 2 3例行肝穿病理诊断。结果　急性病毒性肝炎组CHE和PTA下降率分别为 0 .0 0 %和8.82 % ,急性病毒性肝炎组、慢性病毒性肝炎组、肝炎肝硬化组中CHE和PTA依次降低 (P <0 .0 1) ,且二者之间相关系数为 0 .75 2 (P <0 .0 1) ;12例血清CHE低于 1kU/L和PTA低于 2 0 %的肝硬化患者中 10例死亡 ,病死率为83.33% ,明显增高 (P<0 .0 1)。结论　血清CHE和PTA不能作为急性肝损伤指标 ,却是反映肝脏疾病慢性化、肝脏储备功能和再生功能的良好指标 ,与病情及预后有关