Urinary ethyl glucuronide (uEtG) as a marker for alcohol consumption in liver transplant candidates: a real-world cohort.

BACKGROUND: In order to reduce alcohol relapse after liver transplantation (LT), the German national guidelines for waiting-list maintenance and organ allocation demand a minimum 6-month period of alcohol abstinence pre-LT, confirmed by measuring urinary ethyl glucuronide (uEtG). METHODS: Between January 2015 and June 2016, uEtG was measured at least once in 339 cirrhotic patients with an indication for LT at the University Medical Center Mainz. uEtG was measured with an enzyme-linked immunosorbent assay (ELISA) screening test (cutoff value: 500 µg/L). For uEtG values ≥ 500 µg/L, liquid chromatography-mass spectrometry (LC-MS/MS) was performed as a confirmatory assay. Data were collected prospectively in a transplant database. RESULTS: Of the 339 potential liver transplant candidates, uEtG was negative in 86.4 %. Most patients were male (64.3 %), with an average age of 56.42 ±â€Š10.1 years. In the multivariate analysis, mean corpuscular volume (p = 0.001), urinary creatinine (p = 0.001), gamma-glutamyl transferase (p = 0.001), and hemoglobin (p = 0.003) were significantly associated with a positive uEtG test result. The sensitivity of the ELISA screening test was 100 % for uEtG values > 2000 µg/L, as confirmed by LC-MS/MS. CONCLUSION: uEtG is an effective parameter to reveal alcohol consumption by patients on the waiting list for LT. The sensitivity of the ELISA is excellent for uEtG values > 2000 µg/L, for which LC-MS/MS confirmation could be omitted.

High urinary excretion of lipid peroxidation-derived DNA damage in patients with cancer-prone liver diseases.

Chronic inflammatory processes induce oxidative and nitrative stress that trigger lipid peroxidation (LPO), whereby DNA-reactive aldehydes such as trans-4-hydroxy-2-nonenal (HNE) are generated. Miscoding etheno-modified DNA adducts including 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) are formed by reaction of HNE with DNA-bases which are excreted in urine, following elimination from tissue DNA. An ultrasensitive and specific immunoprecipitation/HPLC-fluorescence detection method was developed for quantifying epsilondA excreted in urine. Levels in urine of Thai and European liver disease-free subjects were in the range of 3-6 fmol epsilondA/micromol creatinine. Subjects with inflammatory cancer-prone liver diseases caused by viral infection or alcohol abuse excreted massively increased and highly variable epsilondA-levels. Groups of Thai subjects (N=21) with chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma (HCC) due to HBV infection had 20, 73 and 39 times higher urinary epsilondA levels, respectively when compared to asymptomatic HBsAg carriers. In over two thirds of European patients (N=38) with HBV-, HCV- and alcohol-related liver disease, urinary epsilondA levels were increased 7-10-fold compared to healthy controls. Based on this pilot study we conclude: (i) high urinary epsilondA-levels, reflecting massive LPO-derived DNA damage in vivo may contribute to the development of HCC; (ii) epsilondA-measurements in urine and target tissues should thus be further explored as a putative risk marker to follow malignant progression of inflammatory liver diseases in affected patients; (iii) etheno adducts may serve as biomarkers to assess the efficacy of (chemo-)preventive and therapeutic interventions.

Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication.

BACKGROUND & AIMS: Leukotrienes are proinflammatory mediators. Ethanol inhibits the catabolism of both cysteinyl leukotrienes (leukotriene E(4) [LTE(4)] and N-acetyl-LTE(4)) and leukotriene B(4) (LTB(4)) in hepatocytes. We examined the metabolic derangement of leukotriene inactivation by ethanol in humans in vivo. METHODS: LTE(4), N-acetyl-LTE(4), LTB(4), and 20-hydroxy-LTB(4) were quantified in urine samples from 16 patients with acute alcohol intoxication (mean blood ethanol, 75 mmol/L). In 9 healthy volunteers, urinary LTE(4) was determined before and after ethanol consumption (mean blood ethanol, 14 mmol/L). RESULTS: The excretion of LTE(4) during alcohol intoxication was 286 compared with 36 nmol/mol creatinine in healthy subjects (P < 0.01); the corresponding values for N-acetyl-LTE(4) were 101 and 11 nmol/mol creatinine, respectively (P < 0.001). This excretion of cysteinyl leukotrienes decreased when the blood ethanol concentration returned to normal. LTB(4) and 20-hydroxy-LTB(4) were detectable only in patients with excessive blood ethanol concentrations (mean, 95 mmol/L). In healthy volunteers, LTE(4) excretion increased 3-5 hours after ethanol consumption (mean peak concentration of 1.5 nmol/L compared with 0.5 nmol/L for basal values; P < 0.005). CONCLUSIONS: Ethanol at high concentration induces increased leukotriene excretion into urine. These changes are consistent with inhibition of leukotriene catabolism and inactivation induced by ethanol, as well as with a higher leukotriene formation caused by ethanol-induced endotoxemia.

Enhanced urinary excretion of cGMP in liver cirrhosis. Relationship to hemodynamic changes, neurohormonal activation, and urinary sodium excretion.

Cyclic guanosine monophosphate (cGMP) has been proposed to mediate peripheral arterial vasodilation in liver cirrhosis. Nitric oxide and natriuretic peptides are the main signals for cGMP generation. Variation in urinary cGMP excretion parallels changes in plasma cGMP levels. Our aim was to determine urinary excretion of cGMP (UcGMPV) and to investigate its relationship to systemic hemodynamics, neurohumoral activity and renal sodium excretion in cirrhosis. Urinary excretion of cGMP was measured in 19 healthy subjects and 20 patients with alcoholic cirrhosis. Systemic hemodynamic parameters, blood volume (BV), plasma atrial natriuretic factor (ANF), and the endothelium-dependent vasodilator substance P (SP) were determined in all patients and in five healthy subjects. Urinary cGMPV was higher in the group of patients (736 pg/min; 50-3229 pg/min) than in controls (126 pg/min; 0-1657 pg/min) (P < 0.01). In addition, UcGMPV inversely correlated with the systemic vascular resistance and directly with cardiac output, blood volume, SP, ANF, and Pugh's score. By Cox regression analysis, only systemic vascular resistance remained inversely associated with UcGMPV. In conclusion, urinary cGMP excretion is increased in cirrhosis. It is suggested that increased cGMP generation may be related to the hyperkinetic circulation in human cirrhosis.

Pharmacokinetics of meropenem in patients with liver disease.

Eight subjects with chronic stable alcoholic cirrhosis and eight matched controls with normal liver function were given an initial 30-minute intravenous infusion of 1 g of meropenem; beginning 24 hours later, they received five additional 1-g doses at 6-hour intervals. No statistically significant differences were found between the first dose and steady state or between groups for any plasma pharmacokinetic parameters-including the highest observed plasma concentrations, plasma concentrations at 6 hours after dosing (C6h), terminal half-life, area under the plasma concentration-time curve (AUC), area under the first moment of the curve, plasma clearance, steady-state volume of distribution, and accumulation ratios-on the basis of either AUC or C6h. There were also no statistically significant differences in any of the measured or calculated pharmacokinetic parameters of the microbiologically inactive metabolite of meropenem (ICI 213,689). A total of 11 adverse experiences (one moderate and 10 mild) were reported by four patients; nine of these experiences, including two in controls, were rated by the investigator as "possibly" drug related. It is concluded that meropenem is well tolerated with repeated intravenous dosing and that dosage adjustments are not necessary for patients with hepatic disease.

Urinary excretion of urodilatin in patients with cirrhosis.

Cirrhotic patients with ascites show increased plasma levels of natriuretic peptides from cardiac origin (i.e., atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]). Urodilatin is a unique member of the natriuretic peptide family because it is exclusively synthesized in the kidney acting on a paracrine fashion in the regulation of sodium excretion. To investigate the renal production of urodilatin in cirrhosis and its relationship with other natriuretic peptides and sodium retention, urodilatin excretion and plasma levels of ANP were measured in 21 healthy subjects, 13 cirrhotic patients without ascites and 23 cirrhotic patients with ascites. Urine urodilatin was measured with a highly specific radioimmunoassay using a polyclonal antibody against human urodilatin. Patients with ascites had marked sodium retention (UNa 7 +/- 2 mEq/d) as compared to patients without ascites and healthy subjects (29 +/- 3 mEq/d and 34 +/- 5 mEq/d, respectively, P < .001). Patients with cirrhosis and ascites had urine urodilatin excretion similar to patients without ascites and healthy subjects (82 +/- 8 pmol/g, 95 +/- 10 pmol/g, and 89 +/- 9 pmol/ g of creatinine, respectively; not significant). In addition, immunoreactive urodilatin from cirrhotic patients with ascites and healthy subjects showed a similar chromatographic pattern. By contrast, plasma ANP levels were increased significantly in patients with ascites (29 +/- 3 fmol/mL) as compared with patients without ascites or healthy subjects (14 +/- 3 fmol/mL and 6 +/- 1 fmol/mL, respectively; P < .01). In conclusion, urine urodilatin excretion is normal in patients with cirrhosis even in the presence of marked sodium retention. The coexistence of increased ANP levels and normal urodilatin excretion suggests that in cirrhosis both natriuretic peptides are regulated independently.

Guanidino compounds in serum and urine of cirrhotic patients.

To investigate the metabolic relationship between urea and guanidinosuccinic acid (GSA), we determined the levels of the guanidino compounds, including GSA, and urea in serum and urine of cirrhotic patients. Linear correlation studies between serum urea and GSA levels were performed. Good positive linear correlation coefficients were found in the Child-Turcotte C subgroup (r = .847, P < .001) and in the total subgroup including B and C patients (r = .848; P < .0001). Serum guanidinoacetic acid levels were significantly increased in the Child-Turcotte C subgroup (P < .0001 for men and P < .001 for women). In contrast, GSA levels were significantly (P < .0001) decreased in the three studied subgroups. Similar results were found for urinary GSA excretion levels. Within each subgroup, serum and urinary GSA levels were significantly lower in patients with alcohol-induced cirrhosis than in nonalcoholic cirrhotic patients. Similar results were obtained for urea. The findings in cirrhotic patients clearly demonstrate a metabolic relationship between urea and GSA. They also show that urea and GSA biosynthesis is significantly lower in cirrhotic patients with an alcoholic origin than in cirrhotic patients with a nonalcoholic origin.

[Directional velocity of the arterial flow, systemic vascular resistance and urinary excretion of sodium in cirrhotic patients]. / Vitesse directionelle du flux artériel, résistance vasculaire systémique et excrétion urinaire du sodium chez les cirrhotiques.

OBJECTIVES: We have studied the vascular resistance at the posterior tibial artery utilizing the Doppler reverse/forward flow ratio, and its relationship to systemic vascular resistance and renal function in 32 nonazotemic cirrhotic patients. METHODS: Patients were divided into three groups. Group A comprised 10 patients without ascites or oedema; group B comprised 9 patients with ascites and a relatively high sodium excretion (40 +/- 34 mmol/day); and group C comprised 13 patients with ascites and very low sodium excretion (4.9 +/- 2 mmol/day). RESULTS: No significant differences were found in urine flow, creatinine or creatinine clearance between the three groups. Renin and aldosterone levels were found increased in group C. Systemic vascular resistance differed significantly in the three groups, being lower in group C. Significant higher values in the Doppler reverse/forward ratio were observed in patients with markedly increased sodium retention and less systemic vascular resistance (group C). The Doppler reverse/forward ratio showed significant correlations with systemic vascular resistance (r = 0.65; n = 32; p < 0.001), urinary sodium excretion (r = 0.53; n = 32; p < 0.01), renin (r = 0.474; n = 32; p < 0.01) and aldosterone levels (r = 0.589; n = 32; p < 0.001). CONCLUSIONS: These preliminary results suggest in patients with hepatic cirrhosis vascular resistance, assessed non-invasively, at the posterior tibial artery, increases with the severity of sodium retention and the impairment in systemic hemodynamics. Thus, this measurement may be useful for the evaluation and follow-up of patients with cirrhosis of the liver.

Severe renal hypouricemia secondary to hyperbilirubinemia.

A 64-year-old man with alcoholic liver cirrhosis had a progressive decrease in the serum uric acid (UA) until it became undetectable, an increase renal UA clearance, mild glycosuria with normal serum glucose and a decrease in the tubular reabsorption of phosphate in association with cholestasis secondary to a gallbladder carcinoma. All these abnormalities returned to normal when the serum bilirubin levels decreased following surgical treatment. This clinical observation suggests that the reversible renal tubular transport defect was secondary to high levels of serum bilirubin.

Effect of the serine protease inhibitor, aprotinin, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites.

1. Previous studies have documented activation of protease enzymes, such as the plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin generation could contribute to pathological systemic vasodilatation in cirrhosis, and reduced systemic vascular resistance has been suggested as a trigger to renal sodium retention in this disease. We investigated the effect of aprotinin, a protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites. 2. Aprotinin was infused intravenously in high dosage (2 x 10(6) kallikrein inhibitory units loading, 1 x 10(6) kallikrein inhibitory units/h). 3. Of 13 patients, 10 had a low systemic vascular resistance (< 1200 dyn s cm-5) at baseline. In this group, eight showed an increase in systemic vascular resistance during aprotinin infusion. Overall, the increase in systemic vascular resistance was significant, and there was a small but significant increase in mean arterial pressure. In all patients, there were increases in renal plasma flow, glomerular filtration rate, and absolute and fractional urinary sodium excretion during aprotinin infusion. 4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell significantly during aprotinin infusion. Plasma prekallikrein, plasma noradrenaline and plasma atrial natriuretic peptide did not change. Plasma aprotinin concentration was 209 +/- 11 kallikrein inhibitory units/ml at the end of the infusion. 5. Before and during the infusion, there was a significant negative correlation between systematic vascular resistance and plasma renin activity. There was a positive correlation between the change in systemic vascular resistance and the change in renal plasma flow during aprotinin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Taurine-induced diuresis and natriuresis in cirrhotic patients with ascites.

Taurine is a non-protein sulfur amino acid widely distributed in mammalian tissues, with poorly understood functions. Taurine administration has a variety of hemodynamic effects, including improvement of cardiac function and suppression of sympathetic activity. Increased urinary volume and sodium excretion have been reported in taurine-fed hamsters. Since patients with ascitic liver cirrhosis have severe hemodynamic and renal abnormalities potentially sensitive to taurine feeding, we evaluated the effects of the i.v. infusion of taurine on urinary flow and sodium excretion and on the hormones involved in the control of hydrosaline homeostasis. Eight cirrhotic patients with tense ascites were given an i.v. bolus of taurine (16 mumoles in 40 ml of saline). The next day patients were given saline only, as a control. Diuresis, urinary sodium and plasma renin activity, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured for the following 6 hrs. Plasma taurine increased ten fold after infusion, then decreased exponentially. No side effects were recorded. After taurine, but not after saline, there was a prompt and significant increase in both urinary volume and sodium excretion. Diuresis increased from 340 +/- 43 to 817 +/- 116 microliters/min (p < 0.01); urinary sodium from 13.8 +/- 3 to 26.3 +/- 4 mumoles/min (p < 0.05). Both values returned to normal after 2-3 hrs. Taurine infusion caused a concomitant significant decrease in plasma renin activity (from 7.7 +/- 2.2 to 4.3 +/- 1.9 ng/ml/hr, p < 0.05) and aldosterone (from 588 +/- 47 to 348 +/- 89 pg/ml, p < 0.05), but no changes in atrial natriuretic peptide and arginine vasopressin. We conclude that i.v. taurine infusion in ascitic cirrhosis promotes a transient diuresis and natriuresis, apparently through the inhibition of the renin-aldosterone axis.

Urinary level of L-fucose as a marker of alcoholic liver disease.

The urinary levels of L-fucose were measured in 93 alcoholics; 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L-fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 +/- 97 vs. 240 +/- 95 mumol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 +/- 29 vs. 155 +/- 60 mumol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 +/- 97 mumol/g of creatinine) than with viral cirrhosis (265 +/- 42 mumol/g of creatinine) (p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.

Refractory ascites: modulation of atrial natriuretic factor unresponsiveness by mannitol.

We have previously shown that unresponsiveness to atrial natriuretic factor is a marker of the severity of ascites. The tubular mechanisms are unknown, but it seems that increased reabsorption of sodium proximal to the main site of action of atrial natriuretic factor (i.e., the inner medullary collecting duct) plays an important role. We attempted to decrease the proximal reabsorption of sodium with mannitol in patients unresponsive to atrial natriuretic factor. The results of mannitol in such a group of patients has previously been conflicting. We studied 10 patients with massive, resistant ascites who were off diuretics and on a 20-mmol/day sodium diet for 7 days. Atrial natriuretic factor unresponsiveness was confirmed by failure of a 2-hr atrial natriuretic factor infusion to induce a natriuresis. The next day all patients received an infusion of 40 gm of mannitol and subsequently a combined infusion of mannitol and atrial natriuretic factor. Proximal reabsorption of sodium and water were evaluated by lithium clearance, and glomerular filtration rate and renal blood flow were evaluated by inulin clearance and p-aminohippurate clearances, respectively. Six patients responded to mannitol alone with an increased diuresis (from 39 +/- 7 to 148 +/- 35 ml/hr) and natriuresis (from 0.27 +/- 0.05 mmol/hr to 1.65 +/- 0.53 mmol/hr; p less than 0.05) (responders), whereas four did not (nonresponders). The combination of atrial natriuretic factor and mannitol induced a further significant increase in sodium excretion (3.28 +/- 0.68 mmol/hr) but not in urine excretion, compared with mannitol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma.

The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were divided into two groups in accordance with their renal function (serum creatinine above/below 180 mumol/l). The fractional excretion of beta 2m (FE-beta 2m) was used to monitor beta 2m elimination. The study failed to show any distinction in FE-beta 2m between HN and ATIN patients, presumably owing to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died as a result of paracetamol intoxication had both abnormal FE-beta 2m and abnormal S-Cr and Cr-Cl, suggesting that if therapy had been initiated earlier, when only FE-beta 2m was affected, these patients might have survived. All patients who survived, except three paracetamol- and one aminoglycoside-intoxicated patient, had normal FE-beta 2m in the beginning of the coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Relation to severity, presence of hepatitis, and alcohol intake.

This study investigated the relationships of the serum markers of fibrogenesis and basement membrane formation to the clinical and morphological severity of alcoholic liver disease and to the degree of alcohol abuse. The concentrations of the aminoterminal propeptide of type III collagen, type IV collagen, and laminin were measured from 87 samples representing a wide range of clinical and histological severities of the disease, which were assessed with indices that have been shown to correlate well with the risk of dying within 1 yr. Significant correlations (p less than 0.00001) were found between the markers of connective tissue metabolism and the Combined Clinical and Laboratory Index: (aminoterminal propeptide of type III collagen, rs = 0.82; type IV collagen, rs = 0.82; laminin, rs = 0.81), as well as between these markers and the Combined Morphological Index: (aminoterminal propeptide of type III collagen, rs = 0.70; type IV collagen, rs = 0.68; laminin, rs = 0.64). Whereas the patients with less than 8 mM of alcohol in their morning urine (mild or moderate drinkers) showed a significant (p less than 0.00001) decrease in these markers in a period of 27 +/- 1 wk, the patients with more than 8 mM of urinary alcohol (heavy drinkers) had no improvement. It is proposed that both fibrogenesis and basement membrane formation are associated with disease severity, degree of alcoholic hepatitis, and alcohol intake, which are important determinants of prognosis in alcoholic liver disease.

Intrarenal thromboxane A2 generation reduces the furosemide-induced sodium and water diuresis in cirrhosis with ascites.

To assess the effects of intrarenal thromboxane A2 generation on furosemide-induced sodium and water excretion we administered furosemide (40 mg i.v.) to 8 nonazotemic cirrhotic patients with ascites and 8 healthy subjects before and after the administration of OKY 046 (200 mg twice orally), a powerful thromboxane-synthase inhibitor. Selective thromboxane-synthase inhibition significantly reduced basal and postfurosemide (1 h) urinary thromboxane B2 excretion in healthy subjects (65% before and 62% after furosemide) as well as in cirrhotic patients (52% before and 67% after furosemide) without affecting urinary prostaglandin E2 and 6-keto prostaglandin F1 alpha excretion. During the first hour after furosemide administration, OKY 046 administration significantly enhanced postfurosemide water excretion (milliliters per minute) in both healthy subjects (from 8.5 +/- 2.0 to 11.6 +/- 2.1, p less than 0.001) and cirrhotic patients (from 1.1 +/- 0.8 to 4.2 +/- 0.5, p less than 0.005), whereas furesemide-induced natriuresis (microequivalents per minute) was significantly increased only in the latter group (from 973 +/- 125 to 1405 +/- 121, p less than 0.05). Our data indicate that intrarenal thromboxane A2 generation, elicited by furosemide administration, may reduce the effects of the drug on water and sodium diuresis. Such a reduction seems to be more marked in the presence of an activated intrarenal prostaglandin system, suggesting that renal thromboxane A2 may represent an additional factor in conditioning the impaired responsiveness to furosemide, which is frequently observed in cirrhotic patients with ascites.

Renal sodium retention in cirrhosis: tubular site and relation to hepatic dysfunction.

Renal sodium handling, assessed by the response to acute saline loading, was investigated in 14 well-compensated, nonascitic alcoholic cirrhotics and six normal controls. Urinary sodium excretion in cirrhotic patients (199 +/- 141 mumoles per min) was significantly lower than in controls (387 +/- 104 mumoles per min; p less than 0.01) at 3 hr postinfusion. In contrast to controls, renal plasma flow and glomerular filtration rate did not increase in the cirrhotics in response to acute saline loading. Proximal fractional reabsorption of sodium was estimated by clearance techniques in the presence of a hypotonic diuresis. Cirrhotic subjects with impaired functional liver cell mass as assessed by antipyrine clearance were unable to decrease proximal fractional reabsorption of sodium significantly in response to saline loading. Assessment in the cirrhotics included measurement of hepatic vein pressure gradient, indocyanine green extraction ratio, indocyanine green clearance, and antipyrine clearance as indices of portal pressure, intrahepatic shunting, hepatic blood flow and functional hepatocellular mass, respectively. Urinary sodium excretion in the cirrhotics correlated strongly with antipyrine clearance (r = 0.839, p less than 0.0001) and weakly with portal pressure (r = 0.562, p = 0.037). No correlation was seen with the other indices of hepatic blood flow and shunting. The findings of this study suggest that alcoholic cirrhosis is associated with a decline in hepatocellular function which results in either a decreased clearance of a salt-retaining hormone or decreased synthesis of a natriuretic hormone.(ABSTRACT TRUNCATED AT 250 WORDS)