HepC BC 
URSODEOXYCHOLIC ACID DECREASES THE SERUM TRANSAMINASE LEVELS OF CHRONIC LIVER DISEASE PATIENTS TREATED WITH GLYCYRRHIZIN
The effects of ursodeoxycholic acid (UDCA) on the liver function test values were investigated in patients with chronic hepatitis (CH) and liver cirrhosis (LC) in whom treatment with glycyrrhizin (SNMC) for more than 6 months had failed to improve serum transaminase levels. Twenty-six patients treated with Stronger neo minophagen C (SNMC), 60 ml, i.v., three times/week) for more than 6 months were given UDCA (Urso, 600 mg/day) in addition (SNMC + UDCA group) and 22 patients were given UDCA (Urso, 600 mg/day) alone (UDCA group). The mean AST, ALT, gamma-GTP and total bile acid (TEA) values during the 3 months before UDCA treatment and the 3 months after the start of UDCA treatment were compared in each case. The results showed that AST, ALT and gamma-GTP were improved by 28, 34 and 46%, respectively in the 24 patients with CH, type C in the SNMC f UDCA group, and 27, 30 and 39%, respectively in the 14 patients with CH, type C in the UDCA group. UDCA was also effective in improving AST and ALT in the patients in the SNMC + UDCA group who were resistant to interferon therapy. The percentages of improvement in AST, ALT and gamma-GTP in the 10 LC patients were lower than in the CH patients in both SNMC f UDCA and UDCA group. In conclusion, UDCA is useful in decreasing the serum transaminase levels of patients with CH, even when they are being treated with SNMC. (C) 1996 Elsevier Science Ireland Ltd.
Author: MITSUYOSHI H, KYOTO PREFECTURAL UNIV MED, DEPT INTERNAL MED 3, KAMIGYO KU, KYOTO 602, JAPAN
Source: INTERNATIONAL HEPATOLOGY COMMUNICATIONS 1996 DEC;6(2):85-91
HepC BC
Viral Hepat 4 (2): 139-141 (1997)
Reduced glutathione concentration in erythrocytes of patients with acuteand chronic viral hepatitis
Swietek K, Juszczyk J Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Reduced glutathione (GSH), the main intracellular mechanism that protects against oxidative stress, is the subject of considerable interest in viral hepatitis. In patients with chronic hepatitis C, results reported from different centres are controversial, demonstrating either a reduction or an elevation of GSH concentration. The aim of this study was to evaluate the glutathione concentration in erythrocytes (normal range 2.45 +/- 0.15 mmol l-1) in patients with acute and chronic viral hepatitis. In 52 patients with acute viral hepatitis (hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection) there was marked reduction of GSH at the beginning of the disease (0.79 +/- 0.43 mmol l-1, P < 0.001) with high alanine aminotransferase (ALT) activity (1549 +/- 772.9 IU l-1). In 37 patients with chronic HCV infection the mean value of GSH was below the normal range (1.92 +/- 0.62 mmol l-1, P < 0.001). In 60% of patients (n = 22), depletion of GSH was observed and 40% (n = 15) presented with a normal concentration of GSH. In 10 patients with chronic HBV infection the mean value of GSH was also below the normal range (1.93 +/- 0.32 mmol l-1, P < 0.001); in 80% of cases (n = 8) depletion of GSH was observed and 20% of patients (n = 2) had normal GSH concentrations. The ALT activity was not significantly different in patients with depleted and normal GSH concentrations (P > 0.05) in groups with chronic HBV and HCV infection.
PMID: 9097271, MUID: 97251589
HepC BC
Bile-acid Inhibition of Interferon Activity in Human-lymphocytes --No Evidence of Oxidative Stress
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION 1997 JUN;27(6):491-496
Cholestasis and bile acids are two factors involved in resistance to interferon therapy in patients with chronic hepatitis C. As bile acids inhibit the biological activity of this cytokine in vitro and are capable of generating oxidative stress in hepatocytes, we investigated the potential involvement of such a mechanism in human lymphocytes. Thus, we evaluated (a) the effects of bile acids (0-200 mu mol L-1) on lymphocyte reduced glutathione content and malondialdehyde production and (b) the ability of antioxidants to prevent the inhibitory effect of chenodeoxycholic acid on interferon -induced lymphocyte 2',5'-oligoadenylate synthetase activity, an index of the biological activity of interferon. We found that treatment of lymphocytes with bile acids for 24 h did not induce malondialdehyde release or significantly modify cellular reduced glutathione content. Synthetic precursors of glutathione (N- acetylcysteine and S-adenosylmethionine) and antioxidants (superoxide dismutase and catalase) had no preventive influence on the inhibitory effect of chenodeoxycholic acid on interferon-induced 2',5'-oligoadenylate synthetase activity. These negative results do not provide evidence for the use of glutathione precursors in cholestatic conditions associated with viral diseases.
AD - PODEVIN P HOP ST ANTOINE,SERV HEPATOL,AP,HOP PARIS,184 RUE FAUBOURG ST ANTOINE F-75012 PARIS, FRANCE
HepC BC Journal of Hepatology
Volume 26 - issue 3 - page 606 - 613
EASL
Glutathione kinetics in normal man and in patients with liver cirrhosis
Giampaolo Bianchi, Elisabetta Bugianesi, Michela Ronchi, Andrea Fabbri, Marco Zoli and Giulio Marchesini
Background/Aims:The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis.
Methods:The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate.
Results:The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests.
Conclusions:The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.
HepC BC KEIKO SHIMIZU-SAITO,1 SABURO HORIKAWA,1 NAOSUKE KOJIMA,2 JUNJI SHIGA,3 HARUKI SENOO,2 AND KINJI TSUKADA1
Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver-type and nonhepatic-type enzymes, which are the products of two different genes. It is known that the liver-type isozyme is only expressed in adult liver. Whereas, the nonhepatic-type isozyme is widely distributed in various tissues. In addition to the liver-type isozyme, a minor amount of the nonhepatic-type isozyme is also detected in adult liver. To investigate the distribution of these two isozymes in the liver in detail, the localization of these two isozymes was examined in each cell type of liver using a combination of cell fractionation technique and Western blot analysis. In the parenchymal cells, the liver-type isozyme protein was predominantly expressed, and a small amount of the nonhepatic-type isozyme protein was also detected. On the other hand, in the stellate cells the nonhepatic-type isozyme protein was exclusively or only expressed. Interestingly, a large amount of both isozymes were present in endothelial and Kupffer cell fraction. Using both antibodies to anti-rat nonhepatic-type and liver-type isozymes, respectively, immunohistochemical analysis clearly confirmed these results. In addition, in cultured hepatocellular carcinoma cells (FAA-HTC1), the nonhepatic-type isozyme protein only was detected, and the liver-type isozyme protein completely disappeared. This result indicates that the changes in the isozyme expression is regulated within the parenchymal cells. Administration of hepatotoxic drug carbon tetrachloride (CCl4) to rats resulted in about 40% to 50% reduction of enzyme activity in parenchymal cells and stellate cells compared with those of control rats. However, enzyme activity in endothelial and Kupffer cell fraction was not changed.
Address reprint requests to: Saburo Horikawa, Ph.D., Department of Pathological Biochemistry, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101, Japan. Fax: 81-3-5280-8081.
Copyright © 1997 by the American Association for the Study of Liver Diseases.
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