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      Significance of Serum Alpha-Glutathione S-Transferase Assessment in Hepatitis C Patients with Different Alanine Aminotransferase Patterns

      research-article
      a , b , c
      Gastroenterology Research
      Elmer Press
      Hepatitis C, Glutathione transferase

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          Abstract

          Background

          Alpha-Glutathione S-transferase (α-GST) is a liver enzyme which showed properties making it useful in assessment of liver cell damage. A number of studies demonstrated its early elevation in different hepatic insults, but its pattern in HCV was controversial. Consequently, we planned this work to study the significance of Serum Alpha-Glutathione S-Transferase (α-GST) assessment in hepatitis C patients with different alanine aminotransferase (ALT) patterns.

          Methods

          Sixty-five untreated male patients with history of hepatitis C virus (HCV) positive antibodies and 21 healthy age- and sex-matched control subjects were enrolled in this study. Sera were collected for confirmation of the presence of HCV antibodies (by ELISA) as well as for assessment of the levels of α-GST, ALT, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl-transferase, total proteins, albumin and HCV RNA. HCV RNA was detected by the reverse transcription polymerase chain reaction (RT-PCR). Based on ALT level, patients were divided into three groups. Twelve patients with normal ALT levels (NALT), 29 with near normal ALT levels (NNALT), and 24 with high ALT levels (HALT). All data were statistically analyzed for significance and correlation as well as sensitivity, specificity, positive and negative predictive values.

          Results

          The mean value of α-GST in HCV patients was significantly higher compared to the control with 82% sensitivity, 85% specificity, 98% positive predictive value and 63% negative predictive value. These results were more or less similar to the results of ALT and higher than the results of all the other assayed liver function tests. The sensitivity, and positive and negative predictive values of α-GST were lower than aminotransferases, but higher than the other assayed liver function tests in NNALT and HALT groups. Nevertheless, in NALT, these parameters were higher for α-GST than all the other assayed liver function tests including aminotransferases.

          Conclusions

          Assay of α-GST has an adjuvant in evaluation of liver cell damage in HCV patients. However, its role is much more valuable in patients with normal aminotransferases for early detection of liver cell damage.

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          Most cited references31

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          The current state of serum biomarkers of hepatotoxicity.

          The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early clinical trials.
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            Epidemiology of hepatitis C virus infection.

            Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.
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              Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors.

              In Egypt, schistosomiasis was traditionally the most important public health problem and infection with Schistosoma mansoni the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic a s treatment f o r schistosomiasis in the entire country. This both reduced schistosomal transmission and disease and interrupted the "occult" HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particutarly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons.
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                Author and article information

                Journal
                Gastroenterology Res
                Gastroenterology Res
                Elmer Press
                Gastroenterology Research
                Elmer Press
                1918-2805
                1918-2813
                February 2011
                20 January 2011
                : 4
                : 1
                : 13-19
                Affiliations
                [a ]Departments of Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
                [b ]Internal Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
                Author notes
                [c ]Corresponding author: hamdy.sliem@ 123456yahoo.com
                Article
                10.4021/gr269w
                5139795
                27957007
                25434125-a71a-432b-a38c-3d0c7ce665ba
                Copyright 2011, Abdel-Moneim et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 December 2010
                Categories
                Original Article

                hepatitis c,glutathione transferase
                hepatitis c, glutathione transferase

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