Cytochrome P-450 CYP2E1 ; metabolism ; Fatty Liver, Alcoholic ; enzymology ; pathology ; Liver ; enzymology

Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; Cyclooxygenase 2 ; metabolism ; Fatty Liver ; enzymology ; pathology ; Hepatitis, Viral, Human ; enzymology ; pathology ; Humans ; Liver Diseases ; enzymology ; pathology ; Liver Diseases, Alcoholic ; enzymology ; pathology ; Liver Neoplasms ; prevention & control

Liver function tests (LFT) are helpful screening tools to detect hepatic dysfunction. LFT are further used to categorize hepatic dysfunctions, to estimate the severity of hepatic disease, and for the follow-up of liver diseases. Since liver performs a variety of functions, no single test is sufficient alone to provide complete estimate of function of liver. Effective interpretation of the hepatic function panel requires knowledge of underlying pathophysiology and the characteristics of panel tests. This review includes a classification of liver diseases, which are commonly detected by routine LFT, a list of liver functions with appropriate tests for each function, and a guide to panel interpretation and further laboratory investigation.
Humans ; Liver/enzymology/metabolism/pathology ; Liver Diseases/blood/*diagnosis ; Liver Function Tests

OBJECTIVETo explore the relationship between the alteration in GGT mRNA expression and the development of HCC.

METHODSThree GGT mRNA types (F, H, and P) in normal liver tissues, diseased liver tissues without HCC, cancerous and noncancerous tissues from livers with HCC, and noncancerous tissues from livers with metastatic tumor were tested by RT-PCR.

RESULTSIn normal livers, the main type of GGT mRNA was type F. In liver diseases but not HCC, the distribution of the type GGT mRNA was nearly the same as in normal livers. The prevalence of type H was significantly higher in both cancerous and noncancerous tissues of livers with HCC than in livers without HCC (P<0.05). The prevalence of type F in cancerous tissues was significantly lower than that in livers without HCC (P<0.05).

CONCLUSIONSThe GGT mRNA expression in the human liver will shift from type F to type H during the development of HCC. The fragment analysis of GGT genes may be a sensitive assay to detect hepatic cell canceration.

Carcinoma, Hepatocellular ; enzymology ; genetics ; pathology ; Female ; Gene Expression Regulation, Enzymologic ; Humans ; Liver ; enzymology ; metabolism ; pathology ; Liver Diseases ; enzymology ; genetics ; pathology ; Liver Neoplasms ; enzymology ; genetics ; pathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; gamma-Glutamyltransferase ; genetics

OBJECTIVETo study the role of arginase-1 (Arg-1) expression in differential diagnosis of hepatocellular carcinoma (HCC), Arg-1 staining pattern in clear cell neoplasm (HCC and non-HCC) and Arg-1 expression in non-hepatocellular tumors.

METHODSSeventy-eight cases of HCC (including 8 cases of clear cell type and 70 cases of non- clear cell type) and 246 cases of non-hepatocellular neoplasms (including 29 cases of metastatic tumors such as breast cancer, nasopharyngeal carcinoma and neuroendocrine carcinoma, 77 cases of tumors with clear cell changes such as malignant melanoma, clear cell renal cell carcinoma and alveolar soft part sarcoma, and 140 cases of other types of tumors such as ovarian endometrioid adenocarcinoma, pituitary tumor and thyroid papillary carcinoma) were studied.Immunohistochemical study for Arg-1 was performed on the paraffin-embedded tumor tissue.

RESULTSIn HCC, Arg-1 demonstrated both cytoplasmic and nuclear staining, with an overall sensitivity of 96.2% (75/78).In well, moderately and poorly differentiated HCC, the sensitivity was 15/15, 100% (41/41) and 86.4% (19/22), respectively. That was in contrast to negative staining for Arg-1 in all the 29 cases of metastatic tumors studied. The sensitivity, specificity, positive predictive value and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors was 96.2%, 100%, 100% and 90.6%, respectively. Cytoplasmic and membranous staining was observed in clear cell type of HCC. The overall sensitivity of Arg-1 expression in the 77 cases of tumors with clear cell changes was 14.3% (11/77), including 8/15 for malignant melanoma, 2/4 for ovarian clear cell carcinoma and 1/1 gall bladder adenocarcinoma with clear cell component.In malignant melanoma and ovarian clear cell carcinoma, only cytoplasmic staining was demonstrated. There was no expression of Arg-1 in the 140 cases of other tumor types studied.

CONCLUSIONSArg-1 is a sensitive and specific marker for HCC.It is a potentially useful immunohistochemical marker in distinguishing HCC from metastatic tumors. Though also expressed in malignant melanoma and ovarian clear cell carcinoma, Arg-1 shows a different staining pattern as compared with that in HCC.

Adenocarcinoma ; enzymology ; Adult ; Aged ; Arginase ; metabolism ; Carcinoma, Hepatocellular ; enzymology ; pathology ; secondary ; Cell Differentiation ; Diagnosis, Differential ; Female ; Gallbladder Neoplasms ; enzymology ; Humans ; Liver Neoplasms ; enzymology ; pathology ; secondary ; Male ; Melanoma ; enzymology ; Middle Aged ; Ovarian Neoplasms ; enzymology ; Stomach Neoplasms ; enzymology ; pathology

OBJECTIVETo investigate the changes of sugar chain structures of alkaline phosphatase (ALP) in hepatoma tissue and its relation to the invasiveness of hepatocellular carcinoma (HCC).

METHODSThe binding ratios of ALP from 9 normal liver tissues, 16 hepatoma tissues and 16 noncancerous tissues surrounding hepatoma were analysed by affinity chromatography on various lectin columns including leukoagglutinating phytohemagglutinin (L-PHA), lentil lectin (LCA), Datura stramonium agglutinin (DSA), erythroagglutinating phytohemagglutinin (E-PHA) and Sambucus nigra bark agglutinin (SNA).

RESULTSThe binding ratios of ALP on L-PHA (22.94%+/-5.30%), DSA (55.97%+/-13.72%), LCA (38.16%+/-8.87%), E-PHA (11.56%+/-4.81%) and SNA (69.80%+/-13.71%) in HCC tissues were significantly increased (P<0.01) compared with that in normal liver tissues (L-PHA 5.89%+/-2.75%, DSA 36.20%+/-11.58%, LCA 17.90%+/-6.71%, E-PHA 5.38%+/-2.20%, SNA 57.32%+/-11.27%), respectively. t values between the two groups were 8.94, 3.64, 5.94, 3.62 and 2.32, respectively. L-PHA-binding ratio (25.84%+/-4.67%) of ALP in HCC with invasiveness was significantly higher than that (18.10%+/-3.64%) without invasiveness (t=3.71, P<0.01).

CONCLUSIONThe changes of ALP sugar chain structures occur in HCC tissue. b1-6 branching sugar chain structure of ALP is related to the invasiveness of HCC.

Alkaline Phosphatase ; chemistry ; Carbohydrates ; chemistry ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Chromatography, Affinity ; Humans ; Lectins ; metabolism ; Liver Neoplasms ; enzymology ; pathology ; Neoplasm Invasiveness

To study the mechanism of endotoxin-induced hepatocellular injury in rats, a single dose of endotoxin, 15mg/kg, was injected intraperitoneally with or without dexamethasone pretreatment. Studies included light microscopic, histochemical, and electron microscopic observations with concomitant assay of free acid phosphatase activity of liver homogenateg. The results showed an increase of acid phosphatase activity as early as 30 minutes after the injection of endotoxin, and by light microscopy random focal necrosis of liver cells at 1 hour and fibrin thrombi formation in sinusoids especially within the area of necrosis at 3 hours. However, ultrastructural alteration was noted as early as 5 minutes after the injection of endotoxin characterized by marked dilatation of RER. The degree of necrosis, fibrin thrombus formation, and the elevation of free acid phosphatase activity in the liver homogenates seemed to parallel each other suggesting a possible interrelationship among these phenomena. However, the ultrastructnral changes of the hepatocytes were present far ahead of the appearance of fibrin thrombi formation. Therefore, the causal relationship of the fibrin thrombi to liver cell injury appeared unlikely. Despite the increase of free acid phosphatase activity in liver homogenates, no demonstrable structural disruption of lysosomal membrane was noted. In view of the prominent changes of RER 5 minutes after the endotoxin administration, the primary injurious effect of endotoxin affects the membrane system of all organelles including the lysosomal membrane, leading to the leakage of lysosomal enzymes into the cytoplasmic sap. Dexamethasone pretreatment alleviated necrosis and markedly inhibited fibrin thrombus formation, and the mechanism of this effect is considered to be a stabilizing effect of glucocorticoid upon membrane systems.
Acid Phosphatase/metabolism ; Animal ; Endotoxins* ; Injections, Intraperitoneal ; Liver/enzymology ; Liver/pathology* ; Liver Diseases/chemically induced ; Liver Diseases/metabolism ; Liver Diseases/pathology* ; Male ; Necrosis ; Rats

OBJECTIVETo investigate the relationship between hepatic lipase activity and fatty degeneration of hepatocytes and explore the effects of tea polyphennols (TP) on the changes of hepatic lipase (HL) activity in rabbits with fatty liver.

METHODSAccording to serum cholesterol and triglyceride (TC) levels, 19 rabbits were divided into fatty liver group (FL, n=6) fed with high cholesterol diet, TP group (n=7) fed with high cholesterol diet and 20mug/g/d tea polyphennols everyday orally, control group (n=6) fed with normal diet. After 8 weeks, the levels of serum TC, HL activity, HL activity and malondildehyde (MDA) in hepatic tissue were detected, and the pathomorphology of hepatic tissue were determined in all rabbits.

RESULTSThe fatty degeneration of hepatocyts in FL group was more severe than that in TP and control group. The serum TC level in TP group (16.87 6.58) mmol/L was higher than that (1.11 0.82) mmol/L in control group (t=5.786, p<0.05), but lower than that (28.49 5.99) mmol/L in FL group (t=3.968, p<0.05). The serum low density lipoprotein-cholesterol level in Tp group (5.10 4.19) mmol/L also higher than that (0.71 1.14) mmol/L in control group (t=3.763, p<0.05), but lower than that (12.15 1.95) mmol/L in FL group (t=2.478, p<0.05). The number of positive dots presenting HL activity level in 100 square micron, hepatic tissue in TP group (3.24 0.17) was higher than that (1.76 0.10) in FL group (t=-3.153, p<0.05), but lower than that (4.14 0.05) in control group (t=-2.902, p<0.05). The levels of MDA in hepatic tissue in TP group (44.66 26.18) nmol/mg was significantly lower than that (75.58 29.88) nmol/mg in FL group (t=2.261, p<0.05), but no evidently different from that (43.64 16.95) nmol/mg in control group. The plasma HL activity was no difference among the three groups.

CONCLUSIONThe HL activity in hepatic tissue with fatty degeneration of hepatocytes was lower than that in normal liver. Tea polyphennols can increase HL activity in hepatic tissue and protect hepatocytes from fatty degeneration.

Animals ; Fatty Liver ; blood ; enzymology ; pathology ; Flavonoids ; Lipase ; metabolism ; Lipids ; blood ; Liver ; enzymology ; metabolism ; pathology ; Male ; Malondialdehyde ; analysis ; Phenols ; pharmacology ; Polymers ; pharmacology ; Polyphenols ; Rabbits ; Tea

OBJECTIVEThe aim of this study was to compare the biochemical and virological characteristics among patients infected with hepatitis B virus (HBV) according to pathologic inflammation grade.

METHODS428 patients with chronic HBV infection accept liver biopsy, liver function test, HBeAg detection and HBV DNA levels detection. They were studied and subdivided into four groups according to pathologic inflammation grade. The biochemical and virological characteristics were studied. Univariate analysis was performed with the SPSS 16.0.

RESULTSIn different inflammation grading group, mean age and sex composition were no difference. Serum levels of ALT was highest in group G3 and lowet in group G0-1, there was statistically significant among groups (P = 0.005); AST and TBil were all highest in group G4 and lowest in group G0-1, statistically significant also found among groups (P = 0.000 & 0.004). Serum levels of ALB and PTA were all highest in group G0-1 and lowest in group G4, had statistically significant among groups (P = 0.000 & 0.000). There was no difference of HBV DNA level and percentage of HBeAg (+) among four groups (P = 0.565 & 0.065).

CONCLUSIONSThe serum AST, TBil, ALB and PTA were different and can partly reflect the inflammation degree of liver damage in patients with HBV infection. ALT and PTA can reflect the inflammation degree of G0-1, G2 and G3; AST, TBil, ALB and PTA reflect the G3 and G4. HBV DNA level and HBeAg status can not indicate the inflammation degree in HBV infection patients.

Adult ; Aged ; Alanine Transaminase ; metabolism ; Female ; Hepatitis B ; enzymology ; immunology ; pathology ; virology ; Hepatitis B virus ; Humans ; Liver ; enzymology ; immunology ; pathology ; virology ; Liver Function Tests ; Male ; Young Adult

NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser extent in the nucleus. Ectopic expression of NM23-H2 in NIH3T3 fibroblasts and HLK3 hepatocytes showed a transformed morphology, enhanced focus formation, and allowed anchorage-independent growth. Finally, NIH3T3 fibroblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice and showed c-Myc over-expression. In addition, NF-kappaB and cyclin D1 expression were also increased by NM23-H2. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors produced from HLK3 cells stably expressing NM23-H2. Collectively, these results indicate that NM23-H2 may be pro-oncogenic in hepatocarcinogenesis.
Animals ; Carcinoma, Hepatocellular/*enzymology/genetics/pathology ; Cell Line ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; Humans ; Liver/*enzymology/metabolism/pathology ; Liver Neoplasms/*enzymology/genetics/pathology ; Mice ; Mice, Nude ; NIH 3T3 Cells ; NM23 Nucleoside Diphosphate Kinases/*genetics/metabolism