Female ; Glucuronosyltransferase ; biosynthesis ; genetics ; Hepatitis B, Chronic ; enzymology ; Hepatitis C, Chronic ; enzymology ; Hepatitis, Chronic ; enzymology ; Humans ; Liver Cirrhosis ; enzymology ; Male ; RNA, Messenger ; biosynthesis ; genetics

Macroenzymes are normal enzymes complexed with an immunoglobulin (usually IgG, rarely IgA or IgM). A number of macroenzymes have been reported in the literature. Among them, macro-AST has been detected in diseases such as acute and chronic hepatitis, various malignancies and autoimmune diseases, but usually not associated with any specific disease. We report a case of elevated AST activity in serum due to marco-AST formation in a female with chronic hepatitis C which was confirmed by AST isoenzyme electrophoresis. To our knowledge, this is the first report of macro-AST occurred in chronic hepatitis patient in Korea.
Aspartate Aminotransferases/*blood ; Female ; Hepatitis C, Chronic/*enzymology ; Humans ; Isoenzymes/blood ; Middle Aged

Telomerase is highly activated in human immortal cell lines and tumor tissues, whereas it is not activated in primary cell strains and many tumor-adjacent tissues. It is suggested that telomerase activation is one of the critical steps in malignant transformation. In the present study, the telomerase activity was investigated in hepatocellular carcinoma tissues and non-tumor liver tissues from Korean patients with chronic hepatitis and cirrhosis. Eighty two liver tissues (24 chronic hepatitis specimens, 34 cirrhosis specimens, and 24 hepatocellular carcinomas) were obtained from 23 chronic viral hepatitis patients, 19 cirrhosis patients (including 7 liver transplants), and 24 patients with hepatocellular carcinoma, of which the surrounding non-tumor liver tissues were available in 16 patients (1 chronic hepatitis and 15 cirrhosis). As negative controls, 3 normal liver tissues were included. Protein from liver specimens was purified by a detergent lysis method as described elsewhere, and telomerase activity was measured in 2 diluents of each sample (1:1 and 1:100) by a telomeric repeat amplification protocol (TRAP). Telomerase was strongly activated in 79% (19/24) of the hepatocellular carcinomas, while weakly in 8% (2/24) of the chronic hepatitis tissues and in 24% (8/34) of the cirrhosis tissues. All of 3 normal control livers showed no telomerase activation. No relationship could be observed between the enhancement of telomerase activity and tumor nature. None of the chronic heaptitis or cirrhosis patients with mild telomerase activation in the liver have developed hepatocellular carcinoma for at least 2 years of follow-up period. These results suggest that the strong enhancement of telomerase activity may be a critical part of hepatocarcinogenesis, although the exact mechanism of such high activation in hepatocellular carcinoma is not clear. In addition, further study will be necessary to clarify the reason why no telomerase activity detectable by a conventional TRAP can be seen in some hepatocellular carcinoma.
Adult ; Aged ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/enzymology* ; Cell Transformation, Neoplastic* ; Comparative Study ; Enzyme Activation ; Female ; Hepatitis, Chronic/enzymology ; Human ; Liver Cirrhosis/enzymology ; Liver Neoplasms/pathology ; Liver Neoplasms/enzymology* ; Male ; Middle Age ; Precancerous Conditions/enzymology* ; Telomerase/analysis*

OBJECTIVETo evaluate the relationship between changes and clinical significance of serum glutamyl transpeptidase (GGT) and the degree of liver lesions in chronic hepatitis B (CHB).

METHODSExaminations of serum ALT, AST, GGT levels and liver biopsy were carried out and classification and staging of liver fibrosis and inflammation were performed for 70 patients with CHB. The relationship between ALT, AST, GGT and CHB was analyzed.

RESULTS(1) ALT, AST and GGT increased with the degree of inflammation and fibrosis, but their levels declined with the degree of G4 and S4. The correlation coefficients of ALT and GGT, AST and GGT were (0.322 and 0.328, P less than 0.05). With liver-protective treatment, in the cases with mild CHB, ALT was normalized quickly but GGT remained at a lower level. While ALT declined, GGT was still at a relatively high level for moderate and severe CHB cases, among them the level of GGT fluctuated.

CONCLUSIONSerum GGT reflects the degree of liver inflammation more accurately than ALT and AST do and GGT activity can provide important evidence for clinical assessment of chronic hepatitis B.

Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Female ; Hepatitis B, Chronic ; drug therapy ; enzymology ; Humans ; Male ; gamma-Glutamyltransferase ; blood

BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.
Adult ; Aged ; Cyclooxygenase 2/analysis/*physiology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Progression ; Female ; Hepatitis, Chronic/enzymology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/drug therapy/*enzymology ; Male ; Middle Aged

OBJECTIVETo investigate the correlation between spontaneous clearance of HBV DNA and the levels of Alanine Aminotransferase (ALT) in chronic hepatitis B (CHB) patients.

METHODSRetrospective review analysis was used in this research. A total of 177 CHB patients with HBV DNA>1x10(4) copies/ml and ALT>800 U/L were recruited in this study and were divided randomly into two groups, 84 patients in control group (received lamivudine therapy) while 96 cases in study group (without anti-viral therapy), the dynamic changes of HBV DNA and HBV markers in these two groups were compared.

RESULTSThe clinical data of CHB patients were retrospected and followed up in 24 weeks. The negative conversion cases of HBV DNA are 62 (87.3%) in study group and 56 cases (78.87%) in control group at week 24, the negative conversion cases of HBV DNA are 56 (78.9%) in study group and 60 (92.3%) cases in control at week 8. No significant difference (x2=0.058, P>0.05) existed between these two groups. Among 43 patients with HBV DNA is less than or equal to 6 log10 copies/ml, 41 (95.3%) patients converted negatively, while in 28 patients with HBV DNA is more than 6 log10 copies/ml, 21 (75.0%) patients converted negatively. The negative conversion rate of HBV DNA is more than 6 log10 copies/ml was lower than the other group at week 24. The difference between the two groups was significant (x2=0.024, P<0.05). 41 patients with hepatitis B e antigen (HBeAg) negative and 30 patients with HBeAg positive were included in antiviral group. The negative conversion cases of HBV DNA of the former are 36 (87.8%) and the latter are 26 (86.7%). No significant difference found between them (x2=1, P>0.05). HBeAg loss found in 10 patients of 30 HBeAg positive patients with 4 patients occurred as early as at the fourth week. A total of 62 patients HBV DNA converted negatively in antiviral group, but 5 patients were found HBV DNA rebounded (occurred in 24 to 72 weeks) with ALT rebound (47 to 140 U/L).

CONCLUSIONSThe tendency of spontaneous clearance of HBV DNA when ALT is more than 800 U/L is obvious, so anti-viral therapy should be administrated strictly. The negative conversion rate of HBV DNA has no relation with HBeAg but with the copies of HBV DNA replication.

Adult ; Alanine Transaminase ; metabolism ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; enzymology ; Humans ; Male ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the intrahepatic expression of inducible nitric oxide synthase (iNOS) in patients with chronic hepatitis B (CHB) and its relation to liver histopathology.

METHODSThe intensity and distribution of the immunohistochemical staining of intrahepatic iNOS were studied in the liver biopsy specimens obtained from 74 patients with CHB and statistical analyses were performed between intrahepatic iNOS and ALT, HbeAg, HBV DNA grading of liver inflammation and staging of fibrosis. Seven histologically normal liver sections were used as a control group.

RESULTSCompared with the control group, the intrahepatic iNOS immunoexpression was significantly higher in patients with CHB (P < 0.05), iNOS immunoreactivity was observed mainly in hepatocytes showing a predominant cytoplasmic staining, with the positive liver cells distributed diffusely throughout the hepatic lobule. Immunopositive staining could also be detected in Kupffer cells, sinusoidal lining cells and vascular endothelial cells. Compared with patients with normal ALT, the hepatocellular iNOS immunoexpression was significantly higher in patients with elevated ALT (P < 0.05) and the iNOS immunoexpression was significantly correlated with the serum level of ALT (r=0.601, P=0.000). Statistical analysis also showed that the intrahepatic iNOS immunoexpression was positively correlated with the grading of liver inflammation and the staging of liver fibrosis (r=0.660, P=0.000; r=0.507, P=0.000). No significant correlation between iNOS and HBeAg and HBV DNA was detected. CONCLUSION The intrahepatic expression of iNOS is elevated in chronic hepatitis B patients and correlated well with the severity of the disease, which indicated that inducible nitric oxide synthase may have a critical role in the pathogenesis of chronic viral hepatitis B.

Adult ; Alanine Transaminase ; metabolism ; DNA, Viral ; metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Hepatitis B Antigens ; metabolism ; Hepatitis B virus ; metabolism ; Hepatitis B, Chronic ; enzymology ; metabolism ; pathology ; virology ; Hepatocytes ; metabolism ; Humans ; Male ; Nitric Oxide Synthase Type II ; metabolism

BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI=1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/*blood ; Female ; Hepatitis B, Chronic/blood/enzymology/*pathology ; Humans ; Liver/pathology ; Liver Cirrhosis/*pathology/virology ; Male ; *Platelet Count ; Sensitivity and Specificity

It is unclear whether serum ALT levels or virological characteristics of hepatitis C virus(HCV) including HCV genotypes and HCV RNA titers, can reflect the degree of histological injury in chronic hepatitis C. The aim of this study was to investigate the relationships between the levels of histological damage and serum ALT levels, HCV genotypes or circulating HCV RNA titers in chronic hepatitis C. A total of 56 patients underwent liver biopsy and the histological activity index (HAI) was evaluated by Knodell's scoring system. HCV genotype by RT-nested PCR and HCV RNA quantitation by competitive RT-PCR were performed. Thirty-four patients were infected with HCV genotype 1b, 20 patients with genotype 2a, and 2 patients with undetermined type. Serum ALT levels were not positively correlated with total HAI score or HCV RNA titers, but showed a linear correlation with scores of piecemeal necrosis (r=0.32, p<0.05) and portal inflammation (r=0.27, p<0.05). HCV genotype had no significant correlation with RNA titers, HAI score or with serum ALT levels. Also, no statistical relationship was seen between HCV RNA titer and HAI score. These results suggest that liver histology is essential to evaluate the severity of chronic hepatitis C precisely.
Adolescence ; Adult ; Aged ; Alanine Transaminase/*blood ; Female ; Genotype ; Hepacivirus/*classification/genetics ; Hepatitis C, Chronic/enzymology/*pathology/virology ; Human ; Male ; Middle Age ; RNA, Viral/*blood

OBJECTIVETo explore the change of serum gamma-glutamyltransferase (GGT) and its diagnosis value in chronic hepatitis B (CHB) patients with different degrees of liver damage.

METHODSAlanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and GGT were measured in 221 CHB patients. Liver biopsy was conducted simultaneously to determine the inflammation grade and fibrosis stage of the liver tissues.

RESULTSThe rate of normal GGT in pathologically diagnosed mild and severe CHB patients was 90.4% and 12.3%, respectively (P<0.01). Increased level of GGT was parallel to the degree of liver pathological change (P<0.01). In active CHB patients, GGT rose with the ALT increase with a positive linear correlation between them (r=0.464, P<0.001). In pathologically diagnosed mild CHB patients, GGT had a tendency of rapidly declining to normal levels with ALT. In moderate CHB patients, GGT fluctuated at a relatively high level, and in severe CHB patients GGT exhibited a deviation from GGT.

CONCLUSIONSGGT is conducive to improve the coincident rate between the clinical and pathological diagnosis of CHB.

Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Female ; Fibrosis ; Hepatitis B, Chronic ; diagnosis ; enzymology ; pathology ; Humans ; Male ; Predictive Value of Tests ; Severity of Illness Index ; Time Factors ; gamma-Glutamyltransferase ; blood