Short Communications Digestion 13: 372-374 (1975)
Normal Serum Gastrin Levels in Patients with Liver Cirrhosis1 H. Pointner First Department of Medicine (Head: Prof. E. Deutsch), University of Vienna, Vienna
Key Words. Gastrin • Liver cirrhosis • Radioimmunoassay Abstract. In 28 patients with cirrhosis of the liver, histologically confirmed by liver biopsy, serum gastrin concentrations were determined radioimmunologically afcr an over night fast. Mean value and standard deviation in the patients with cirrhosis (30.1 t 19.3 pg/ml) was not found to be significantly different from the mean value established in 275 normal subjects (39.7 ± 21.3 pg/ml).
In one of the last issues of this journal, Mazzacca et al. (8) reported on elevated serum gastrin levels radioimmunologically measured in patients with cirrhosis of the liver. In their discussion, the authors take into account that the high serum gastrin concentration might be responsible for the high incidence of peptic ulcers in patients with liver cirrhosis. By this short communication we would like to report on serum gastrin levels, radioimmunologically measured in patients with liver cirrhosis, in which we could not find elevated serum gastrin as compared to normal subjects.
Material and Methods Blood was taken after an overnight fast from 28 patients with cirrhosis of the liver, and serum gastrin was measured radioimmunologically. The diagnosis of liver cirrhosis was histo logically confirmed in all patients by liver biopsy. There was no selection of the patients, the etiology of liver cirrhosis being both chronic alcoholism and viral hepatitis. No patient showed signs of renal insufficiency, none had undergone portocaval shunt operation.
Received: September 9, 1975; accepted: September 12, 1975.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 8:40:16 AM
‘ With the assistance of the ‘Österreichischer Fonds zur Förderung der wissenschaft lichen Forschung’, project No. 1505.
Pointner
373
Serum gastrin was measured by radioimmunoassay following the method of Yalow and Berson (12) using the gastrin kit from CEA (Gif/Yvette, France). The kit consists of gastrin antibodies, raised in rabbits with synthetic human gastrin I (SHG I), 131 l-labelled SHG I, and SHG 1 as standard gastrin. Mean fasting values for serum gastrin concentration have been previously established by this radioimmunoassay in 275 normal healthy subjects. These values served us as controls for the values determined in the cirrhotic patients.
Results Mean serum gastrin concentration and standard deviation was found to be 39.7 ± 21.3 pg/ml in 275 healthy subjects. In the 28 patients with liver cirrhosis, the mean serum gastrin concentration and standard deviation was 30.1 ± 19.3 pg/ml. These values are not significantly different from those of the nor mals.
Our results clearly differ from those of Mazzacca et al. (8) in that we could not find elevated serum gastrin concentrations in patients with liver cirrhosis. We cannot offer a simple explanation for this discrepancy. However, our results agree well with studies on gastrin metabolism which had shown that gastrin degradation predominantly takes place in the kidney (3 -5 ) and the small intes tine (2, 6,11) and that the liver plays only a minor role in gastrin metabolism (6, 7, 9, 11). On the other hand, there are reports which could demonstrate by bioassay the presence of a gastrosecretagogue activity in the urine of patients with liver cirrhosis, suggesting by these results a possible influence of the liver on gastrin degradation (1, 10). We want to point at the fact that by bioassay not only gastrin is measured but any compound with gastric acid-stimulating activ ity. Therefore, it is possible that different results obtained by bioassay and radioimmunoassay introduce, due to the methodical difference, false conclusions into the question of the importance of the liver in gastrin metabolism. The most obvious difference of our examination from the study of Maz zacca et al. (8), which both use radioimmunological determination for gastrin, is that these authors examined the serum gastrin concentration under the influence of previously administered atropine, while our patients did not receive such a medication. Therefore, we see the results of Mazzacca et al. as a contribution to the problem of atropine action in patients with liver cirrhosis in comparison to normal subjects rather than a contribution to the question of gastrin pattern in this disease. Finally, it seems doubtful to us that the very small difference in the gastrin levels between cirrhotic and normal subjects, as reported by Mazzacca et al. (8), might be responsible for the increased ulcer incidence in patients with liver cirrhosis.
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Discussion
Pointner
374
References
Dr. Herwig Pointner, 1. Medizinische Universitätsklinik, Lazarettgasse 14, A -1097 Wien (Austria)
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1 Bader, J.P.; Dubrasquet, M B o n fils, S.; Bernades, P.; Lewin, M., and Lambiing, A.: A study of the gastrosecretagogue power of urine (P.S.U.) before and after portocaval anastomosis in man. Scand. J. Gastroent. 4: 65-73 (1969). 2 Becker, H.D.; Reeder, D.D., and Thompson, J.C.: Extraction of circulating endogenous gastrin by the small bowel. Gastroenterology 65: 903-906 ( 1973). 3 Booth, R.A.D.. Reeder, D.D.: Hjelmquist, U.B.; Brandt. E.N.. and Thompson, J.C.: Renal inactivation of endogenous gastrin in dogs. Archs. Surg., Chicago 106: 851-854 (1973). 4 Davidson, W.D.; Springberg, P.D., and Falkinburg, .MR.: Renal extraction and excre tion of endogenous gastrin in the dog. Gastroenterology 64: 955-961 (1973). 5 Dent, R.I.: Levine, B.: Hirsch, H.: James, H., and Fischer, J.E.: Changes in plasma gastrin levels during isolated perfusions of canine lung and kidney. J. surg. Res. 14: 353 358(1973). 6 Dette, G.A. and Seelig. H P.: Gastrin degradation by particle free supernatants of liver and small bowel homogenates of the rat. Acta hepato-gastroenterol. 20: 248-253 (1973). 7 l.anciault, G.: Gislon, J.; Accary, J.P., and Bonfils, S.: The tissue distribution of tritiated gastrin and pentagastrin in the rat. Proc. Soc. exp. Biol. Med. 148: 1081-1086 (1975). 8 Mazzacca, G.: Budilton. G.: De Marco. and De Ritis, F.: Serum gastrin in patients with cirrhosis of the liver. Digestion 11: 232-239 (1974). 9 Reeder, D.D.: Brandt, E.N.: Watson, L.C.: Hjelmquist, U.B., and Thompson, J.C.: Preand posthepatic measurements of mass of endogenous gastrin. Surgery, St Louis 72: 34-41 (1972). 10 Schmidt, H.A.: Khalik, F.. and Martini. G.A.: A study of gastric acid stimulating substances in the urine of patients with liver cirrhosis. Acta hepato-gastroenterol. 19: 271-276 (1972). 11 Temperley. J.M.; Stagg, B.H., and Wyllie, J.H.: Disappearance of gastrin and pentagas trin in the portal circulation. Gut 12: 372-376 (1971). 12 Yalow. R.S. and Berson, S.A.: Radioimmunoassay of gastrin. Gastroenterology 58: 1-14 (1970).
Normal Serum Gastrin Levels in Patients with Liver Cirrhosis1 H. Pointner First Department of Medicine (Head: Prof. E. Deutsch), University of Vienna, Vienna
Key Words. Gastrin • Liver cirrhosis • Radioimmunoassay Abstract. In 28 patients with cirrhosis of the liver, histologically confirmed by liver biopsy, serum gastrin concentrations were determined radioimmunologically afcr an over night fast. Mean value and standard deviation in the patients with cirrhosis (30.1 t 19.3 pg/ml) was not found to be significantly different from the mean value established in 275 normal subjects (39.7 ± 21.3 pg/ml).
In one of the last issues of this journal, Mazzacca et al. (8) reported on elevated serum gastrin levels radioimmunologically measured in patients with cirrhosis of the liver. In their discussion, the authors take into account that the high serum gastrin concentration might be responsible for the high incidence of peptic ulcers in patients with liver cirrhosis. By this short communication we would like to report on serum gastrin levels, radioimmunologically measured in patients with liver cirrhosis, in which we could not find elevated serum gastrin as compared to normal subjects.
Material and Methods Blood was taken after an overnight fast from 28 patients with cirrhosis of the liver, and serum gastrin was measured radioimmunologically. The diagnosis of liver cirrhosis was histo logically confirmed in all patients by liver biopsy. There was no selection of the patients, the etiology of liver cirrhosis being both chronic alcoholism and viral hepatitis. No patient showed signs of renal insufficiency, none had undergone portocaval shunt operation.
Received: September 9, 1975; accepted: September 12, 1975.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 8:40:16 AM
‘ With the assistance of the ‘Österreichischer Fonds zur Förderung der wissenschaft lichen Forschung’, project No. 1505.
Pointner
373
Serum gastrin was measured by radioimmunoassay following the method of Yalow and Berson (12) using the gastrin kit from CEA (Gif/Yvette, France). The kit consists of gastrin antibodies, raised in rabbits with synthetic human gastrin I (SHG I), 131 l-labelled SHG I, and SHG 1 as standard gastrin. Mean fasting values for serum gastrin concentration have been previously established by this radioimmunoassay in 275 normal healthy subjects. These values served us as controls for the values determined in the cirrhotic patients.
Results Mean serum gastrin concentration and standard deviation was found to be 39.7 ± 21.3 pg/ml in 275 healthy subjects. In the 28 patients with liver cirrhosis, the mean serum gastrin concentration and standard deviation was 30.1 ± 19.3 pg/ml. These values are not significantly different from those of the nor mals.
Our results clearly differ from those of Mazzacca et al. (8) in that we could not find elevated serum gastrin concentrations in patients with liver cirrhosis. We cannot offer a simple explanation for this discrepancy. However, our results agree well with studies on gastrin metabolism which had shown that gastrin degradation predominantly takes place in the kidney (3 -5 ) and the small intes tine (2, 6,11) and that the liver plays only a minor role in gastrin metabolism (6, 7, 9, 11). On the other hand, there are reports which could demonstrate by bioassay the presence of a gastrosecretagogue activity in the urine of patients with liver cirrhosis, suggesting by these results a possible influence of the liver on gastrin degradation (1, 10). We want to point at the fact that by bioassay not only gastrin is measured but any compound with gastric acid-stimulating activ ity. Therefore, it is possible that different results obtained by bioassay and radioimmunoassay introduce, due to the methodical difference, false conclusions into the question of the importance of the liver in gastrin metabolism. The most obvious difference of our examination from the study of Maz zacca et al. (8), which both use radioimmunological determination for gastrin, is that these authors examined the serum gastrin concentration under the influence of previously administered atropine, while our patients did not receive such a medication. Therefore, we see the results of Mazzacca et al. as a contribution to the problem of atropine action in patients with liver cirrhosis in comparison to normal subjects rather than a contribution to the question of gastrin pattern in this disease. Finally, it seems doubtful to us that the very small difference in the gastrin levels between cirrhotic and normal subjects, as reported by Mazzacca et al. (8), might be responsible for the increased ulcer incidence in patients with liver cirrhosis.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 8:40:16 AM
Discussion
Pointner
374
References
Dr. Herwig Pointner, 1. Medizinische Universitätsklinik, Lazarettgasse 14, A -1097 Wien (Austria)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 8:40:16 AM
1 Bader, J.P.; Dubrasquet, M B o n fils, S.; Bernades, P.; Lewin, M., and Lambiing, A.: A study of the gastrosecretagogue power of urine (P.S.U.) before and after portocaval anastomosis in man. Scand. J. Gastroent. 4: 65-73 (1969). 2 Becker, H.D.; Reeder, D.D., and Thompson, J.C.: Extraction of circulating endogenous gastrin by the small bowel. Gastroenterology 65: 903-906 ( 1973). 3 Booth, R.A.D.. Reeder, D.D.: Hjelmquist, U.B.; Brandt. E.N.. and Thompson, J.C.: Renal inactivation of endogenous gastrin in dogs. Archs. Surg., Chicago 106: 851-854 (1973). 4 Davidson, W.D.; Springberg, P.D., and Falkinburg, .MR.: Renal extraction and excre tion of endogenous gastrin in the dog. Gastroenterology 64: 955-961 (1973). 5 Dent, R.I.: Levine, B.: Hirsch, H.: James, H., and Fischer, J.E.: Changes in plasma gastrin levels during isolated perfusions of canine lung and kidney. J. surg. Res. 14: 353 358(1973). 6 Dette, G.A. and Seelig. H P.: Gastrin degradation by particle free supernatants of liver and small bowel homogenates of the rat. Acta hepato-gastroenterol. 20: 248-253 (1973). 7 l.anciault, G.: Gislon, J.; Accary, J.P., and Bonfils, S.: The tissue distribution of tritiated gastrin and pentagastrin in the rat. Proc. Soc. exp. Biol. Med. 148: 1081-1086 (1975). 8 Mazzacca, G.: Budilton. G.: De Marco. and De Ritis, F.: Serum gastrin in patients with cirrhosis of the liver. Digestion 11: 232-239 (1974). 9 Reeder, D.D.: Brandt, E.N.: Watson, L.C.: Hjelmquist, U.B., and Thompson, J.C.: Preand posthepatic measurements of mass of endogenous gastrin. Surgery, St Louis 72: 34-41 (1972). 10 Schmidt, H.A.: Khalik, F.. and Martini. G.A.: A study of gastric acid stimulating substances in the urine of patients with liver cirrhosis. Acta hepato-gastroenterol. 19: 271-276 (1972). 11 Temperley. J.M.; Stagg, B.H., and Wyllie, J.H.: Disappearance of gastrin and pentagas trin in the portal circulation. Gut 12: 372-376 (1971). 12 Yalow. R.S. and Berson, S.A.: Radioimmunoassay of gastrin. Gastroenterology 58: 1-14 (1970).
