- Email: [email protected]
Breath hydrogen in bacterial overgrowth
GASTROENTEROLOGY
1989:96:1225-31
CORRESPONDENCE Readers are encouraged to write Letters to the Editor r.oncerning articles that have been published in GASTROENTEROLOGY. Short, general comments are also considered, but use of the Correspondence Section for publication of original data in preliminary form is not encouraged. Letters should be typewritten double-spaced and submitted in triplicate.
Breath
Hydrogen
in Bacterial
Overgrowth
bacteriennes chroniques Biol (in press).
du gr8le prosimal.
Gastroent&ol
Clin
Dear Sir: We have read with great interest the article by Kerlin and Wong (1). We agree with their findings that a 2-h glucose breath hydrogen (H,) test is a simple indirect diagnostic test for bacterial
lsaacs PET, Kim YS. Blind loop syndrome bacterial contamination. Clin Gastroenterol
overgrowth of the small intestine. In a retrospective study (2) we compared the results of breath H, tests and jejunal bacterial cultures in 73 patients admitted for diarrhea with steatorrhea. Bacterial overgrowth was defined as a jejunal culture yielding at least 10” organisms/ml and 10’ anaerobes/ml (3-5). Ilsing these criteria, jejunal cultures were positive in 45 patients and negative in 28 patients. After dietary preparation and a 12-h fast, subjects received 50 g of glucose in 250 ml of water and end-expiratorv breath samples were collected before and at 0.5-h intervals for-4 h. As false-positive breath tests could be expected in patients without overgrowth if there was rapid gastric emptying and intestinal transit of glucose to the cecum. we used a method for measuring the orocecal transit time and for assessing the timing of H, production. Assuming that glucose solution and barium sulfate had the same transit time, 30 ml of
patients with small intestine bacterial overgrowth. Gastroenterology 1986;91:1447-51. Harzic M, Girard-Pipau F. Halphen M. Ferchal F, PBrol I’. Kambaud JC. Etude bact&iologique, parasitologique et virologique de la flore digestive dans la m&die des chaines alpha. Castroenttirol Clin Biol 1985:9:472-9.
barium sulfate was added to the glucose solution and abdominal x-rays were performed every hour for 4 h after the beginning of the test. An abnormal breath H, test was defined as a sustained increase in breath H, excretion of at least 10 ppm and results were analyzed in different ways. Based on a rise of breath H, levels occurring before the deliver\! of barium sulfate to the cecum. the breath H, test had a sensitivity of 73% and a specificity of 89% in the diagnosis of small intestinal bacterial overgrowth. When results were analyzed without taking into account the radiographic location of HL production, the 2-h glucose breath H, test had a sensitivity of 78% and a specificity of 89%, and extending the analysis of results to 3 and 4 h increased sensitivity slightly (80%) but decreased specificity (79% and 68%. respectively). In summary. we welcome the data presented by Kerlin and Wong 11) and confirm that the 50-g glucose breath H, test provides a simple screen for bacterial overgrowth. Addition of barium sulfate to better locate the site of H, production increases the specificity of a 4-h glucose breath H2 test, but does not lead to a greater accuracy compared with a 2-h 50-g glucose breath H1 test, and both complicates the test and exposes patients to abdominal radiation.
Serlrice de Gastroent6rologie HBpitoi Saint-Luzare 75010 Paris. France 1. Kerlin
P. Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology 1988:95:982-8. 2. Flouri B. Turk J. LBmann M. Florent C. Colimon R, Rambaud JC. Valeur diagnostique du test respiratoire $ l’hydrogitne apr6s ingestion de 50 g de n-glucose en cas de contaminations
King CE, Toskes PP. Comparison lo-gram lactulose-Hi,. and 80.gram
Atria1 Natriuretic Factor Patients With Ascites
and small bowel 1983;12:395-414.
of the I-gram [ “C]xylose. glucose-H, breath tests in
in Cirrhotic
Dear Sir: We were interested in the paper by Klepetko et al. [I) who reported that plasma atria1 natriuretic factor (ANF) is not reduced in cirrhosis with ascites. but rises after peritoneovenous shunting. LYe would like to take this opportunity to provide some data that support their findings. Previous investigators have reported plasma ANF concentrations in cirrhosis as high (2-6). normal (7.8). or low (Y). Although some of these differences may reflect variations in the assay used, they may also be due to differences in the c.onditions of study, such as diuretic therapy and sodium intakt,. which are known to alter plasma ANF concentrations. We have measured plasma ANF in cirrhotic patients under a variety ot conditions of diuretic therapy and sodium intake and in control subjects matched for these variables as well as for age and sex. Atria1 natriuretic factor was extracted from plasma [containing aprotinin) by Sep Pat Cl8 cartridges and measured by radioimmunoassay using an antibody against synthetic human l-28 ANF (10). Median plasma ANF concentrations (supine. Casting] were as follows: (a) 10 cirrhotic patients Ivho bad Ilever had ascites (outpatients. no diuretics, unrestricted sodium intake]: 27.2 pgiml [range, 8.1-67.2): (b) 12 cirrhotic patients whose ascites had been cleared by diuretic therapy [outpatients. regular diuretics stopped 72 h before the study. daily sodium intake of 8CI~lOO mmol): 37.6 pg/ml [range, 16.1-163.0): [r:) 11 cirrhotic: patirnts with ascites intake uf -10 mmol): 50.0 (inpatients. no diuretics, daily sodium pg:ml (range. 20.0-338.0): (d) 25 c:onlrnl subjects (equally distributed among the three conditions of study): :i:j.:< pgiml (range. 5.6X31.2). Analysis of variance yielded no significant differences between the four groups (F = 2.5. p 7 0.064). although there is a trend toward higher levels in the ascitic. group. These results support those of Klepelho et
1226
CORRESPONDENCE
GASTROENTEROLOGY
hardt (7), we found a significant correlation between ANF and norepinephrine in cirrhosis (r = 0.60, p < 0.001). Although this relationship is not necessarily causal, it could provide an explanation for normal or even increased plasma ANF despite vascular underfilling. The consensus view must now be that the sodium retention of ascites is not due primarily to a lack of plasma ANF. ALASTAIR J. MAcCILCHRIST JOHN L. REID University Department of Materia Stobhill Hospital Glasgow, Scotland
Medica
1. Klepetko W, Miiller Ch, Hartter E, Miholics J. Schwarz Ch. Woloszczuk W, Moeschl P. Plasma atria1 natriuretic factor in cirrhotic patients with ascites. Effect of peritonovenous shunt implantation. Gastroenterology 1988;95:764-70. 2. Fernandez-Cruz A, Marco J, Cuadrado LM, et al. Plasma levels of atria1 natriuretic peptide in cirrhotic patients. Lancet 1985:ii:1439-40. 3. Arendt RM. Gerbes AL, Ritter D, Stargl E, Back P, Zahringer J. Atria1 natriuretic factor in plasma of patients with arterial hypertension, heart failure or cirrhosis of the liver. J Hypertens 1986;4(Suppl 2):S131-5. 4. Gines P, Jimenez W, Navason M, et al. Atria1 natriuretic factor (ANF) in cirrhosis: plasma levels, cardiac release and splanchnic extraction. J Hepatol 1986;3(Suppl l):S30. 5. Vine1 JP, Denoyel P, Chabrier P, Cales P, Pascal JP. Relationships between atria1 natriuretic factor, plasma renin activity and plasma volume in cirrhotic patients with and without ascites (abstr). Gastroenterology 1987;92:1789. 6. Gerbes AL, Arendt RM. Ritter D, Jungst D, Zahringer J. Paumgarner G. Plasma atria1 natriuretic factor in patients with cirrhosis. N Engl J Med 1985;313:1609-10. 7. Wernze H, Burghardt W. Atria1 natriuretic peptide, the sympathetic nervous system and decompensated cirrhosis. Lancet 1986:i:331. 8. Burghardt W, Diehl K-L, Wernze H. Atria1 natriuretic peptide is not increased in compensated and decompensated cirrhosis: relation to sodium excretion, plasma catecholamines, renin and aldosterone. J Hepatol 1986;3(Suppl l):S31. 9. Simon D, Bonkovsky H, Hartle D, McCain R, Wells J. Galambos J. Atria1 natriuretic peptides (ANP) in cirrhosis: effect of therapeutic paracentesis (abstr). Gastroenterology 1987;92: 1777. 10. Gutkowska J, Horky K, Thibault G. et al. Direct radioimmunoassay of atria1 natriuretic factor. Biochem Biophys Res Commun 1984;122:593-601. 11. Gerbes AL, Arendt RM, Zahringer J, Paumgartner G. Atria1 natriuretic peptide, the sympathetic nervous system and decompensated cirrhosis. Lancet 1986:i:331. 12. Witte CL, Martinez AP, Witte MH. Plasma atriopeptin before and after peritoneojugular venous shunt for hepatogenic ascites. N Engl J Med 1987:316:487. 13. Currie MG, Newman WH. Evidence for a-I-adrenergic receptor regulation of atriopeptin release from the isolated rat heart. Biochem Biophys Res Commun 1986;137:94-100. Reply. Dr. MacGilchrist and Dr. Reid produced valuable data on plasma ANF levels in various groups of patients with liver cirrhosis that showed that no difference exists between patients with ascites and those without. They suggest that their findings and the results of our study can be taken as an argument against the underfilling theory of ascites formation. However, as these authors correctly point out. our data also demonstrate a striking increase of ANF plasma levels after peritoneovenous shunting.
Vol. 96, No. 4
indicating an undisturbed ANF release from atria1 myocardium by the stimulus of volume expansion. We believe, however, that the data gathered on ANF levels in cirrhosis are not sufficient to be used as an argument against the underfilling theory. As patients with cirrhosis have a “relative” hypovolemia in their systemic vascular bed, ANF levels well within the range of normal also can be considered in parallel as “relatively” low. In our opinion, the only conclusion that can be drawn from the described appropriate increase after volume expansion by peritoneovenous shunting is that ANF is not the hitherto unidentified hormonal natriuretic factor, the production of which is proposed to be diminished by the overflow theory of ascites formation. We agree, therefore, with the statement of the authors that the sodium retention in cirrhosis is not due primarily to a lack of plasma ANF. CHRISTIAN MOLLER. M.D. WALTER KLEPETKO. M.D. ENGELBERT HARTTER, M.D.. Ph.D Departments of Gastroenterology, and Medicine University of Vienna Vienna. Austria
Hepatology.
Surgery
Dear Sir: the changes of atria1 natriuretic Klepetko et al. (1) demonstrated factor (ANF] plasma levels in patients with vascularly decompensated liver cirrhosis after peritoneovenous shunt implantation. The intravascular volume expansion due to peritoneovenous shunting resulted in a rise of the plasma ANF level after the operation. The authors suggest that their results support the underfilling concept in the process of sodium excretion and fluid retention. Our experiences seam not to be in full agreement with the conclusions of Klepetko et al. We investigated the plasma concentration of ANF, aldosterone (A), vasopressin (AVP). and plasma renin activity (PRA) in 15 patients with vascularly decompensated liver cirrhosis under basal conditions and after intravascular volume expansion due to the infusion of 1.0 g/kg of hyperoncotic albumin (2). Based on the initial ANF values, it is obvious that cirrhotic patients do not represent a homogeneous group in view of ANF concentration. Concentration was decreased in 9 patients (19.5 + 3.0 fmoliml, group l), but increased (36.7 2 3.9 fmol/ml, group 2) in 6 patients compared with the group of healthy subjects (25.8 ? 2.4 fmol/ml). The initial concentration of PRA (4.4 2 1.0 ng of angiotensin I per milliliter per hour) and AVP (8.5 + 1.5 pgiml) were significantly (p < 0.001) elevated in group 1 compared with the levels in group 2 (PRA: 0.44 + 0.009; AVP: 4.1 ? 0.5). There was no remarkable difference in the values of aldosterone in the two groups. Albumin-induced volume expansion changed the renal and hormonal parameters only in patients with decreased initial ANF values. Sodium excretion (from 40 ? 6.8 to 147 + 20 pmol/min). urine volume (from 0.7 2 0.2 to 2.4 t 0.2 ml/min), and ANF (to 49.5 2 6.6 fmol/ml] increased significantly (p < O.OOl), whereas PRA (to 1.9 -C 0.3 ng of angiotensin I per milliliter per hour) and the plasma level of AVP (to 6.5 2 0.8 pgiml) decreased significantly (p < 0.001). These changes did not develop in patients of group 2. Our findings suggest the role of deficient ANF in the pathophysiology of ascites formation in cirrhotic patients. In the first patient group the decreased activity of ANF and a stimulation of the reninaldosterone system contributed to the altered renal sodium metabolism and the increased activity of AVP caused water retention. On the other hand, in the patients of group 2. an elevated
1989:96:1225-31
CORRESPONDENCE Readers are encouraged to write Letters to the Editor r.oncerning articles that have been published in GASTROENTEROLOGY. Short, general comments are also considered, but use of the Correspondence Section for publication of original data in preliminary form is not encouraged. Letters should be typewritten double-spaced and submitted in triplicate.
Breath
Hydrogen
in Bacterial
Overgrowth
bacteriennes chroniques Biol (in press).
du gr8le prosimal.
Gastroent&ol
Clin
Dear Sir: We have read with great interest the article by Kerlin and Wong (1). We agree with their findings that a 2-h glucose breath hydrogen (H,) test is a simple indirect diagnostic test for bacterial
lsaacs PET, Kim YS. Blind loop syndrome bacterial contamination. Clin Gastroenterol
overgrowth of the small intestine. In a retrospective study (2) we compared the results of breath H, tests and jejunal bacterial cultures in 73 patients admitted for diarrhea with steatorrhea. Bacterial overgrowth was defined as a jejunal culture yielding at least 10” organisms/ml and 10’ anaerobes/ml (3-5). Ilsing these criteria, jejunal cultures were positive in 45 patients and negative in 28 patients. After dietary preparation and a 12-h fast, subjects received 50 g of glucose in 250 ml of water and end-expiratorv breath samples were collected before and at 0.5-h intervals for-4 h. As false-positive breath tests could be expected in patients without overgrowth if there was rapid gastric emptying and intestinal transit of glucose to the cecum. we used a method for measuring the orocecal transit time and for assessing the timing of H, production. Assuming that glucose solution and barium sulfate had the same transit time, 30 ml of
patients with small intestine bacterial overgrowth. Gastroenterology 1986;91:1447-51. Harzic M, Girard-Pipau F. Halphen M. Ferchal F, PBrol I’. Kambaud JC. Etude bact&iologique, parasitologique et virologique de la flore digestive dans la m&die des chaines alpha. Castroenttirol Clin Biol 1985:9:472-9.
barium sulfate was added to the glucose solution and abdominal x-rays were performed every hour for 4 h after the beginning of the test. An abnormal breath H, test was defined as a sustained increase in breath H, excretion of at least 10 ppm and results were analyzed in different ways. Based on a rise of breath H, levels occurring before the deliver\! of barium sulfate to the cecum. the breath H, test had a sensitivity of 73% and a specificity of 89% in the diagnosis of small intestinal bacterial overgrowth. When results were analyzed without taking into account the radiographic location of HL production, the 2-h glucose breath H, test had a sensitivity of 78% and a specificity of 89%, and extending the analysis of results to 3 and 4 h increased sensitivity slightly (80%) but decreased specificity (79% and 68%. respectively). In summary. we welcome the data presented by Kerlin and Wong 11) and confirm that the 50-g glucose breath H, test provides a simple screen for bacterial overgrowth. Addition of barium sulfate to better locate the site of H, production increases the specificity of a 4-h glucose breath H2 test, but does not lead to a greater accuracy compared with a 2-h 50-g glucose breath H1 test, and both complicates the test and exposes patients to abdominal radiation.
Serlrice de Gastroent6rologie HBpitoi Saint-Luzare 75010 Paris. France 1. Kerlin
P. Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology 1988:95:982-8. 2. Flouri B. Turk J. LBmann M. Florent C. Colimon R, Rambaud JC. Valeur diagnostique du test respiratoire $ l’hydrogitne apr6s ingestion de 50 g de n-glucose en cas de contaminations
King CE, Toskes PP. Comparison lo-gram lactulose-Hi,. and 80.gram
Atria1 Natriuretic Factor Patients With Ascites
and small bowel 1983;12:395-414.
of the I-gram [ “C]xylose. glucose-H, breath tests in
in Cirrhotic
Dear Sir: We were interested in the paper by Klepetko et al. [I) who reported that plasma atria1 natriuretic factor (ANF) is not reduced in cirrhosis with ascites. but rises after peritoneovenous shunting. LYe would like to take this opportunity to provide some data that support their findings. Previous investigators have reported plasma ANF concentrations in cirrhosis as high (2-6). normal (7.8). or low (Y). Although some of these differences may reflect variations in the assay used, they may also be due to differences in the c.onditions of study, such as diuretic therapy and sodium intakt,. which are known to alter plasma ANF concentrations. We have measured plasma ANF in cirrhotic patients under a variety ot conditions of diuretic therapy and sodium intake and in control subjects matched for these variables as well as for age and sex. Atria1 natriuretic factor was extracted from plasma [containing aprotinin) by Sep Pat Cl8 cartridges and measured by radioimmunoassay using an antibody against synthetic human l-28 ANF (10). Median plasma ANF concentrations (supine. Casting] were as follows: (a) 10 cirrhotic patients Ivho bad Ilever had ascites (outpatients. no diuretics, unrestricted sodium intake]: 27.2 pgiml [range, 8.1-67.2): (b) 12 cirrhotic patients whose ascites had been cleared by diuretic therapy [outpatients. regular diuretics stopped 72 h before the study. daily sodium intake of 8CI~lOO mmol): 37.6 pg/ml [range, 16.1-163.0): [r:) 11 cirrhotic: patirnts with ascites intake uf -10 mmol): 50.0 (inpatients. no diuretics, daily sodium pg:ml (range. 20.0-338.0): (d) 25 c:onlrnl subjects (equally distributed among the three conditions of study): :i:j.:< pgiml (range. 5.6X31.2). Analysis of variance yielded no significant differences between the four groups (F = 2.5. p 7 0.064). although there is a trend toward higher levels in the ascitic. group. These results support those of Klepelho et
1226
CORRESPONDENCE
GASTROENTEROLOGY
hardt (7), we found a significant correlation between ANF and norepinephrine in cirrhosis (r = 0.60, p < 0.001). Although this relationship is not necessarily causal, it could provide an explanation for normal or even increased plasma ANF despite vascular underfilling. The consensus view must now be that the sodium retention of ascites is not due primarily to a lack of plasma ANF. ALASTAIR J. MAcCILCHRIST JOHN L. REID University Department of Materia Stobhill Hospital Glasgow, Scotland
Medica
1. Klepetko W, Miiller Ch, Hartter E, Miholics J. Schwarz Ch. Woloszczuk W, Moeschl P. Plasma atria1 natriuretic factor in cirrhotic patients with ascites. Effect of peritonovenous shunt implantation. Gastroenterology 1988;95:764-70. 2. Fernandez-Cruz A, Marco J, Cuadrado LM, et al. Plasma levels of atria1 natriuretic peptide in cirrhotic patients. Lancet 1985:ii:1439-40. 3. Arendt RM. Gerbes AL, Ritter D, Stargl E, Back P, Zahringer J. Atria1 natriuretic factor in plasma of patients with arterial hypertension, heart failure or cirrhosis of the liver. J Hypertens 1986;4(Suppl 2):S131-5. 4. Gines P, Jimenez W, Navason M, et al. Atria1 natriuretic factor (ANF) in cirrhosis: plasma levels, cardiac release and splanchnic extraction. J Hepatol 1986;3(Suppl l):S30. 5. Vine1 JP, Denoyel P, Chabrier P, Cales P, Pascal JP. Relationships between atria1 natriuretic factor, plasma renin activity and plasma volume in cirrhotic patients with and without ascites (abstr). Gastroenterology 1987;92:1789. 6. Gerbes AL, Arendt RM. Ritter D, Jungst D, Zahringer J. Paumgarner G. Plasma atria1 natriuretic factor in patients with cirrhosis. N Engl J Med 1985;313:1609-10. 7. Wernze H, Burghardt W. Atria1 natriuretic peptide, the sympathetic nervous system and decompensated cirrhosis. Lancet 1986:i:331. 8. Burghardt W, Diehl K-L, Wernze H. Atria1 natriuretic peptide is not increased in compensated and decompensated cirrhosis: relation to sodium excretion, plasma catecholamines, renin and aldosterone. J Hepatol 1986;3(Suppl l):S31. 9. Simon D, Bonkovsky H, Hartle D, McCain R, Wells J. Galambos J. Atria1 natriuretic peptides (ANP) in cirrhosis: effect of therapeutic paracentesis (abstr). Gastroenterology 1987;92: 1777. 10. Gutkowska J, Horky K, Thibault G. et al. Direct radioimmunoassay of atria1 natriuretic factor. Biochem Biophys Res Commun 1984;122:593-601. 11. Gerbes AL, Arendt RM, Zahringer J, Paumgartner G. Atria1 natriuretic peptide, the sympathetic nervous system and decompensated cirrhosis. Lancet 1986:i:331. 12. Witte CL, Martinez AP, Witte MH. Plasma atriopeptin before and after peritoneojugular venous shunt for hepatogenic ascites. N Engl J Med 1987:316:487. 13. Currie MG, Newman WH. Evidence for a-I-adrenergic receptor regulation of atriopeptin release from the isolated rat heart. Biochem Biophys Res Commun 1986;137:94-100. Reply. Dr. MacGilchrist and Dr. Reid produced valuable data on plasma ANF levels in various groups of patients with liver cirrhosis that showed that no difference exists between patients with ascites and those without. They suggest that their findings and the results of our study can be taken as an argument against the underfilling theory of ascites formation. However, as these authors correctly point out. our data also demonstrate a striking increase of ANF plasma levels after peritoneovenous shunting.
Vol. 96, No. 4
indicating an undisturbed ANF release from atria1 myocardium by the stimulus of volume expansion. We believe, however, that the data gathered on ANF levels in cirrhosis are not sufficient to be used as an argument against the underfilling theory. As patients with cirrhosis have a “relative” hypovolemia in their systemic vascular bed, ANF levels well within the range of normal also can be considered in parallel as “relatively” low. In our opinion, the only conclusion that can be drawn from the described appropriate increase after volume expansion by peritoneovenous shunting is that ANF is not the hitherto unidentified hormonal natriuretic factor, the production of which is proposed to be diminished by the overflow theory of ascites formation. We agree, therefore, with the statement of the authors that the sodium retention in cirrhosis is not due primarily to a lack of plasma ANF. CHRISTIAN MOLLER. M.D. WALTER KLEPETKO. M.D. ENGELBERT HARTTER, M.D.. Ph.D Departments of Gastroenterology, and Medicine University of Vienna Vienna. Austria
Hepatology.
Surgery
Dear Sir: the changes of atria1 natriuretic Klepetko et al. (1) demonstrated factor (ANF] plasma levels in patients with vascularly decompensated liver cirrhosis after peritoneovenous shunt implantation. The intravascular volume expansion due to peritoneovenous shunting resulted in a rise of the plasma ANF level after the operation. The authors suggest that their results support the underfilling concept in the process of sodium excretion and fluid retention. Our experiences seam not to be in full agreement with the conclusions of Klepetko et al. We investigated the plasma concentration of ANF, aldosterone (A), vasopressin (AVP). and plasma renin activity (PRA) in 15 patients with vascularly decompensated liver cirrhosis under basal conditions and after intravascular volume expansion due to the infusion of 1.0 g/kg of hyperoncotic albumin (2). Based on the initial ANF values, it is obvious that cirrhotic patients do not represent a homogeneous group in view of ANF concentration. Concentration was decreased in 9 patients (19.5 + 3.0 fmoliml, group l), but increased (36.7 2 3.9 fmol/ml, group 2) in 6 patients compared with the group of healthy subjects (25.8 ? 2.4 fmol/ml). The initial concentration of PRA (4.4 2 1.0 ng of angiotensin I per milliliter per hour) and AVP (8.5 + 1.5 pgiml) were significantly (p < 0.001) elevated in group 1 compared with the levels in group 2 (PRA: 0.44 + 0.009; AVP: 4.1 ? 0.5). There was no remarkable difference in the values of aldosterone in the two groups. Albumin-induced volume expansion changed the renal and hormonal parameters only in patients with decreased initial ANF values. Sodium excretion (from 40 ? 6.8 to 147 + 20 pmol/min). urine volume (from 0.7 2 0.2 to 2.4 t 0.2 ml/min), and ANF (to 49.5 2 6.6 fmol/ml] increased significantly (p < O.OOl), whereas PRA (to 1.9 -C 0.3 ng of angiotensin I per milliliter per hour) and the plasma level of AVP (to 6.5 2 0.8 pgiml) decreased significantly (p < 0.001). These changes did not develop in patients of group 2. Our findings suggest the role of deficient ANF in the pathophysiology of ascites formation in cirrhotic patients. In the first patient group the decreased activity of ANF and a stimulation of the reninaldosterone system contributed to the altered renal sodium metabolism and the increased activity of AVP caused water retention. On the other hand, in the patients of group 2. an elevated