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IOSR Journal of Pharmacy (IOSRPHR)
ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 69-71
www.iosrphr.org

         Study of serum gamma glutamyl transferase as a diagnostic
                       marker in alcoholic hepatitis
     1
         Dr.J.b gogoi, 2Dr. Praveen k.Tyagi, 3Dr. Amit k.Singh, 4Dr. Kailash gairola
1
    Dr Javin Bishnu Gogoi, MBBS, MD (Biochemistry)Associate professor cum HOD, Dept of Biochemistry,VCSG
          Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174
    2
      Dr Praveen K. Tyagi, MBBS, MS (General Surgery)Assistant professor, Dept of General Surgery,VCSG Govt
             Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174
          3
            Dr. Amit Kumar Singh, MBBS, MD (Community Medicine)Associate professor, Dept of Community
                  Medicine,VCSG Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri),
                                          Uttarakhand, India, Pin-246174
        4
          Dr Kailash Gairola, MBBS,MD (Biochemistry)Senior Demonstrator, Dept of Biochemistry,VCSG Govt
             Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174


Abstract––Serum gamma glutamyl transferase (GGT or γ-GT) is a microsomal enzyme, catalyzes the
transfer of the gamma-glutamyl moiety of glutathione to various peptide acceptors. It is a reliable
diagnostic marker of alcohol ingestion which is one of the most sensitive and most commonly employed
biochemical marker of alcohol consumption . This study was carried out with 30 alcoholic hepatitis and
30 normal non-alcoholic control subjects. The aim of this study was to establish the role of serum GGT
alone in the diagnosis of alcoholic hepatitis. A significant correlation in the level of serum GGT is
observed in alcoholics when compared with the normal subjects. The enzyme activity of GGT in serum is
increased in average by 527.31% in the patients with alcoholic hepatitis compared to normal control
subjects (p<0.05). Measurement of GGT in serum appears to be a sensitive index with low specificity in
the diagnosis of alcoholics with hepatitis when correlated clinically.

Keywords––Alcoholic hepatitis, Gamma glutamyl transferase or transpeptidase (GGT or γ-GT),
Alcoholics.

                                          I.      INTRODUCTION
          Gamma glutamyl transferase or transpeptidase (GGT or γ-GT) is a microsomal enzyme with a wide
tissue distribution. It is a membrane-bound glycoprotein enzyme, catalyzes the transfer of the gamma-glutamyl
moiety of glutathione to various peptide acceptors. However serum GGT is an enzyme having special relation
with alcoholic liver diseases. GGT is a widely used clinical marker of alcohol abuse1. This biliary canalicular
enzyme is induced by alcohols and its serum level rises in response to acute hepatocellular damage2.
          Alcoholism ranks as one of the main current threats to the health and safety of people in most countries
of the world. Chronic alcoholism is considered as a social disease or health related problem inflicting a good
sum of population globally. Alcoholic liver disease is a leading cause of morbidity and mortality worldwide 3.
Therefore, a high priority should be given to aim at reducing its prevalence through more effective diagnosis
and early intervention. The need for objective methods for revealing alcohol abuse in its early phase has also
been widely acknowledged.4
          A variety of liver enzymes assist in the diagnosis of alcohol addiction; including, gamma-glutamyl
transferase (GGT), the most sensitive and widely employed marker, alanine aminotransferase (ALT) and
aspartate aminotransferase (AST). GGT is one of the longest established biochemical tests for excessive alcohol
consumption. GGT is an enzyme in bile, which is induced to rise by alcohol and serum levels due to liver
damage2,5.

                                    II.       METHODS AND MATERIALS
         The present study was carried out with 60 cases out of which 30 cases were established alcoholic
hepatitis patients. The control group (30 cases) was selected from non alcoholic normal, healthy male
volunteers. Blood samples were collected from the two groups for determination of the activity of GGT in
serum. The patients selected for the study were free from infective hepatitis as well as the samples were
collected before the start of treatment to prevent any change of GGT due to drugs administration.
Inclusion criteria:
         (1)       History of alcoholism
                                                       69
Study of serum gamma glutamyl transferase as a diagnostic….

        (2)      Clinical and biochemical evidences of hepatic abnormality
        (3)      Ultrasonographic evidence
        (4)      Histopathological examination
Exclusion criteria-
    1. Infective hepatitis cases
    2. Alcoholic cases who has started treatment
        The results were analyzed statistically by student’s t test.

                                   III.     RESULTS AND DISCUSSION
        In this chapter an effort would be made to correlate the present findings with the results of the previous
workers and to discuss the subject as a whole.
        The serum GGT level in alcoholic hepatitis group was compared to the activity of this enzyme in 30
normal controls.
        The results are represented in table-1

     GROUP                                         SERUM GGT U/L                                SD
                                                   (average value)                              ±
     ALCOHOLIC HEPATITIS (n=30)                    107.73                                       10.45
     NORMAL (n=30)                                 20.43                                        7.72

     Bar diagram 1:-Showing Serum GGT (average value in U/L) in Alcoholic hepatitis and control group



                          120
                           100
                            80
                            60
                             40
                             20
                                0

                                    ALCOHOLIC HEPATITIS
                                          (n=30)                   NORMAL (n=30)




          The average normal serum GGT level is 20.43 ±7.72 U/L in the control group. As against this value in
alcoholic hepatitis, the increase in serum GGT is seen by 527.31 % (p<0.05) with an average value of 107.73
±10.45 U/L.
          GGT is extremely sensitive to alcohol use and serum GGT is one of the best markers for chronic
alcohol consumption, which has a relatively high sensitivity and specificity6. When the increase in GGT is two
or more times greater than the increase in ALP, the source of the ALP is considered to be from the liver. When
the increase in GGT is five or more times greater than the increase in ALP, this point to a diagnosis of alcoholic
hepatitis.7 The serum level of this enzyme gets elevated in cholestasis and hepatobiliary disorder and by drugs
including alcohol possibly due to enzyme induction. Levels parallels serum ALP in cholestasis and may be used
to confirm that a raised serum ALP is of hepato biliary origin 8. Especially high levels of serum GGT are seen in
patients with severe alcoholic liver disease though they may fall in the later stages of cirrhosis. 9 The serum GGT
is markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis whereas mean hepatic
GGT is significantly elevated only in the alcoholic liver disease group.10 Serum GGT is the most sensitive, most
widely employed marker of alcohol consumption. It is more likely to be elevated in regular rather than episodic
drinkers.3, 11 An isolated rise in serum GGT is seen in patients with alcohol abuse, even without liver disease,
                                                        70
Study of serum gamma glutamyl transferase as a diagnostic….

perhaps because of microsomal enzyme induction. More often there is steatosis. In fibrosis, cirrhosis and
hepatitis due to alcohol, other liver enzymes are elevated in conjunction with GGT. 12 Matsuda et al in 1993
classified GGT responses to alcoholic drinking into 3 groups: non response, mild response and hyper response.
In alcoholic liver disease non responders were scarcely found and the response of GGT tended to increase in
parallel with progression of liver disease. 13 Still some workers find that assay of GGT in serum is a misleading
test and measurement of hepatic mitochondrial AST as a new marker enzyme in chronic alcoholism. However,
the results of the present investigation signify the importance of measurement of serum GGT as a diagnostic
marker in alcoholic hepatitis.
There are no reliable markers to detect heavy drinking or as a tool to control abstinence compliance in alcoholic
treatments. The Mean Corpuscular Volume (MCV), and the gammaglutamyl transpeptidase (GGT), are widely
used although their predictive value is somewhat limited due to their low specificity. 14
          This marker may be very useful in opportunistic case finding, in motivating patients to change drinking
habit and in monitoring the treatment response.5

                                                   IV.        CONCLUSION
         This conventional test is widely available and relatively inexpensive. Though having limited sensitivity
and specificity in detection of excessive drinking, it also provide valuable data on complications of drinking and
comorbid conditions that may be affected by drinking and, in some cases, prognosis. This study thus is
indicative of hepatic microsomal injury in chronic alcoholics supporting the findings of earlier workers. Hence,
determination of serum GGT in alcoholic hepatitis will be a useful diagnostic tool if used judiciously and
correlated clinically. Also to be noted that estimation of GGT is more informative in detecting alcoholism if it is
used along with other biochemical parameters like ALT, AST, ALP, MCV, etc.

                                                         REFERENCES
  [1].    Puukka K, Hietala J, Koivisto H, Anttila P, Bloigu R, Niemelä O. Obesity and the clinical use of serum GGT activity as a marker
          of heavy drinking. Scand J Clin Lab Invest. 2007; 67 (5):480-8.)
  [2].    Subir Kumar Das, Prasunpriya Nayak and D.M.Vasudevan. Biochemical markers for alcohol consumption. IJCB, 2003, 18(2)
          111-118.
  [3].    J.B. Gogoi, S.K. Gupta, P.K. Mishra, B. Karunanand. Alcohol abuse and alcoholic hepatitis in upper Assam. Indian J. Prev. Soc.
          Med. Vol 39 No. 1&2, 2008; 28-29.
  [4].    Niemelä O. Biomarkers in alcoholism. Clin Chim Acta. 2007 Feb; 377(1-2):39-49.)
  [5].    Conigrave, KM, Davies, P., Haber, P. and Whitfield, JB. Traditional markers of excessive alcohol use. Addiction, 2003; 98: 31–
          43
  [6].    Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of
          bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995;333:1171-5
  [7].    Jennifer Heisler, RN, About.com Updated: March 1, 2009
  [8].    Rosalki SB. Gamma – glutamyl Transpeptidase. Adv. Clinical Chemistry. 1975; 17: 53.
  [9].    Wu. A., Slavin, G. and Levi, A. J.: Eleveted serum GGT and histological liver damage in alcoholism. Am. J. Gastroenterol 65,
          1976:318-323.
  [10].   Selinger M. J. et al: “GGT activity in liver disease”: ClinChim. Acta: Nov.10, 1982: 125 (3): 283-90.
  [11].   Rosalki, S. (1984) – Identifying the alcoholic. In clinical Biochem. of Alcoholism, (Ed. Rosalki S) PP. 65-92. Churchill,
          Livingstone, Edinburgh.
  [12].   Ireland A, Hartley L, Ryley N et al.: Raised Gamma-Glutamyl-transferase activity and the need for liver biopsy. Br. Med.J.-
          1991; 302 : 388.
  [13].   Matsuda Y et al: “The relationship between the development of alcoholic liver and pancreatic disease and induction of GGT:
          Alcohol suppl: 1B: 27-33, 1993.
  [14].   Glasinovic JC, Lobos X, Scrivanti M, Severín MC, Quiroga T, Moncada C. Carbohydrate deficient transferrin, gammaglutamyl
          transferase and mean corpuscular volume in the evaluation of recent alcohol intake in excessive drinkers. Rev Med Chil. 2001
          Apr; 129(4):375-81).




                                                                  71

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  • 1. IOSR Journal of Pharmacy (IOSRPHR) ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 69-71 www.iosrphr.org Study of serum gamma glutamyl transferase as a diagnostic marker in alcoholic hepatitis 1 Dr.J.b gogoi, 2Dr. Praveen k.Tyagi, 3Dr. Amit k.Singh, 4Dr. Kailash gairola 1 Dr Javin Bishnu Gogoi, MBBS, MD (Biochemistry)Associate professor cum HOD, Dept of Biochemistry,VCSG Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174 2 Dr Praveen K. Tyagi, MBBS, MS (General Surgery)Assistant professor, Dept of General Surgery,VCSG Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174 3 Dr. Amit Kumar Singh, MBBS, MD (Community Medicine)Associate professor, Dept of Community Medicine,VCSG Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174 4 Dr Kailash Gairola, MBBS,MD (Biochemistry)Senior Demonstrator, Dept of Biochemistry,VCSG Govt Medical Science & Research Institute,Srikot, Srinagar (Pauri), Uttarakhand, India, Pin-246174 Abstract––Serum gamma glutamyl transferase (GGT or γ-GT) is a microsomal enzyme, catalyzes the transfer of the gamma-glutamyl moiety of glutathione to various peptide acceptors. It is a reliable diagnostic marker of alcohol ingestion which is one of the most sensitive and most commonly employed biochemical marker of alcohol consumption . This study was carried out with 30 alcoholic hepatitis and 30 normal non-alcoholic control subjects. The aim of this study was to establish the role of serum GGT alone in the diagnosis of alcoholic hepatitis. A significant correlation in the level of serum GGT is observed in alcoholics when compared with the normal subjects. The enzyme activity of GGT in serum is increased in average by 527.31% in the patients with alcoholic hepatitis compared to normal control subjects (p<0.05). Measurement of GGT in serum appears to be a sensitive index with low specificity in the diagnosis of alcoholics with hepatitis when correlated clinically. Keywords––Alcoholic hepatitis, Gamma glutamyl transferase or transpeptidase (GGT or γ-GT), Alcoholics. I. INTRODUCTION Gamma glutamyl transferase or transpeptidase (GGT or γ-GT) is a microsomal enzyme with a wide tissue distribution. It is a membrane-bound glycoprotein enzyme, catalyzes the transfer of the gamma-glutamyl moiety of glutathione to various peptide acceptors. However serum GGT is an enzyme having special relation with alcoholic liver diseases. GGT is a widely used clinical marker of alcohol abuse1. This biliary canalicular enzyme is induced by alcohols and its serum level rises in response to acute hepatocellular damage2. Alcoholism ranks as one of the main current threats to the health and safety of people in most countries of the world. Chronic alcoholism is considered as a social disease or health related problem inflicting a good sum of population globally. Alcoholic liver disease is a leading cause of morbidity and mortality worldwide 3. Therefore, a high priority should be given to aim at reducing its prevalence through more effective diagnosis and early intervention. The need for objective methods for revealing alcohol abuse in its early phase has also been widely acknowledged.4 A variety of liver enzymes assist in the diagnosis of alcohol addiction; including, gamma-glutamyl transferase (GGT), the most sensitive and widely employed marker, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GGT is one of the longest established biochemical tests for excessive alcohol consumption. GGT is an enzyme in bile, which is induced to rise by alcohol and serum levels due to liver damage2,5. II. METHODS AND MATERIALS The present study was carried out with 60 cases out of which 30 cases were established alcoholic hepatitis patients. The control group (30 cases) was selected from non alcoholic normal, healthy male volunteers. Blood samples were collected from the two groups for determination of the activity of GGT in serum. The patients selected for the study were free from infective hepatitis as well as the samples were collected before the start of treatment to prevent any change of GGT due to drugs administration. Inclusion criteria: (1) History of alcoholism 69
  • 2. Study of serum gamma glutamyl transferase as a diagnostic…. (2) Clinical and biochemical evidences of hepatic abnormality (3) Ultrasonographic evidence (4) Histopathological examination Exclusion criteria- 1. Infective hepatitis cases 2. Alcoholic cases who has started treatment The results were analyzed statistically by student’s t test. III. RESULTS AND DISCUSSION In this chapter an effort would be made to correlate the present findings with the results of the previous workers and to discuss the subject as a whole. The serum GGT level in alcoholic hepatitis group was compared to the activity of this enzyme in 30 normal controls. The results are represented in table-1 GROUP SERUM GGT U/L SD (average value) ± ALCOHOLIC HEPATITIS (n=30) 107.73 10.45 NORMAL (n=30) 20.43 7.72 Bar diagram 1:-Showing Serum GGT (average value in U/L) in Alcoholic hepatitis and control group 120 100 80 60 40 20 0 ALCOHOLIC HEPATITIS (n=30) NORMAL (n=30) The average normal serum GGT level is 20.43 ±7.72 U/L in the control group. As against this value in alcoholic hepatitis, the increase in serum GGT is seen by 527.31 % (p<0.05) with an average value of 107.73 ±10.45 U/L. GGT is extremely sensitive to alcohol use and serum GGT is one of the best markers for chronic alcohol consumption, which has a relatively high sensitivity and specificity6. When the increase in GGT is two or more times greater than the increase in ALP, the source of the ALP is considered to be from the liver. When the increase in GGT is five or more times greater than the increase in ALP, this point to a diagnosis of alcoholic hepatitis.7 The serum level of this enzyme gets elevated in cholestasis and hepatobiliary disorder and by drugs including alcohol possibly due to enzyme induction. Levels parallels serum ALP in cholestasis and may be used to confirm that a raised serum ALP is of hepato biliary origin 8. Especially high levels of serum GGT are seen in patients with severe alcoholic liver disease though they may fall in the later stages of cirrhosis. 9 The serum GGT is markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis whereas mean hepatic GGT is significantly elevated only in the alcoholic liver disease group.10 Serum GGT is the most sensitive, most widely employed marker of alcohol consumption. It is more likely to be elevated in regular rather than episodic drinkers.3, 11 An isolated rise in serum GGT is seen in patients with alcohol abuse, even without liver disease, 70
  • 3. Study of serum gamma glutamyl transferase as a diagnostic…. perhaps because of microsomal enzyme induction. More often there is steatosis. In fibrosis, cirrhosis and hepatitis due to alcohol, other liver enzymes are elevated in conjunction with GGT. 12 Matsuda et al in 1993 classified GGT responses to alcoholic drinking into 3 groups: non response, mild response and hyper response. In alcoholic liver disease non responders were scarcely found and the response of GGT tended to increase in parallel with progression of liver disease. 13 Still some workers find that assay of GGT in serum is a misleading test and measurement of hepatic mitochondrial AST as a new marker enzyme in chronic alcoholism. However, the results of the present investigation signify the importance of measurement of serum GGT as a diagnostic marker in alcoholic hepatitis. There are no reliable markers to detect heavy drinking or as a tool to control abstinence compliance in alcoholic treatments. The Mean Corpuscular Volume (MCV), and the gammaglutamyl transpeptidase (GGT), are widely used although their predictive value is somewhat limited due to their low specificity. 14 This marker may be very useful in opportunistic case finding, in motivating patients to change drinking habit and in monitoring the treatment response.5 IV. CONCLUSION This conventional test is widely available and relatively inexpensive. Though having limited sensitivity and specificity in detection of excessive drinking, it also provide valuable data on complications of drinking and comorbid conditions that may be affected by drinking and, in some cases, prognosis. This study thus is indicative of hepatic microsomal injury in chronic alcoholics supporting the findings of earlier workers. Hence, determination of serum GGT in alcoholic hepatitis will be a useful diagnostic tool if used judiciously and correlated clinically. Also to be noted that estimation of GGT is more informative in detecting alcoholism if it is used along with other biochemical parameters like ALT, AST, ALP, MCV, etc. REFERENCES [1]. Puukka K, Hietala J, Koivisto H, Anttila P, Bloigu R, Niemelä O. Obesity and the clinical use of serum GGT activity as a marker of heavy drinking. Scand J Clin Lab Invest. 2007; 67 (5):480-8.) [2]. Subir Kumar Das, Prasunpriya Nayak and D.M.Vasudevan. Biochemical markers for alcohol consumption. IJCB, 2003, 18(2) 111-118. [3]. J.B. Gogoi, S.K. Gupta, P.K. Mishra, B. Karunanand. Alcohol abuse and alcoholic hepatitis in upper Assam. Indian J. Prev. Soc. Med. Vol 39 No. 1&2, 2008; 28-29. [4]. Niemelä O. Biomarkers in alcoholism. Clin Chim Acta. 2007 Feb; 377(1-2):39-49.) [5]. Conigrave, KM, Davies, P., Haber, P. and Whitfield, JB. Traditional markers of excessive alcohol use. Addiction, 2003; 98: 31– 43 [6]. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995;333:1171-5 [7]. Jennifer Heisler, RN, About.com Updated: March 1, 2009 [8]. Rosalki SB. Gamma – glutamyl Transpeptidase. Adv. Clinical Chemistry. 1975; 17: 53. [9]. Wu. A., Slavin, G. and Levi, A. J.: Eleveted serum GGT and histological liver damage in alcoholism. Am. J. Gastroenterol 65, 1976:318-323. [10]. Selinger M. J. et al: “GGT activity in liver disease”: ClinChim. Acta: Nov.10, 1982: 125 (3): 283-90. [11]. Rosalki, S. (1984) – Identifying the alcoholic. In clinical Biochem. of Alcoholism, (Ed. Rosalki S) PP. 65-92. Churchill, Livingstone, Edinburgh. [12]. Ireland A, Hartley L, Ryley N et al.: Raised Gamma-Glutamyl-transferase activity and the need for liver biopsy. Br. Med.J.- 1991; 302 : 388. [13]. Matsuda Y et al: “The relationship between the development of alcoholic liver and pancreatic disease and induction of GGT: Alcohol suppl: 1B: 27-33, 1993. [14]. Glasinovic JC, Lobos X, Scrivanti M, Severín MC, Quiroga T, Moncada C. Carbohydrate deficient transferrin, gammaglutamyl transferase and mean corpuscular volume in the evaluation of recent alcohol intake in excessive drinkers. Rev Med Chil. 2001 Apr; 129(4):375-81). 71