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53 PROGNOSTIC FACTORS IN ALCOHOLIC CIRRHOSIS Bradbear R, Jenkins WJ, Ashby D*, Sherlock S. Depts of Medicine and Epidemiology*, Royal Free Hospital School of Medicine, Pond Street, London, NW3 2PF, UK. To identify factors which'influence the life expectancy of patients with alcoholic cirrhosis we analysed survival data from 138 consecutive patients admitted to this hospital in 1980 and 1981. All patients were followed until death or until the end of the study in February 1984. Clinical, laboratory and histological variables which are routinely recorded were screened and the relative risk associated with each variable was calculated. At the end of the study 67 patients were alive and 71 were dead. Only 17 deaths could not definitely be accounted for by complications of cirrhosis. The following abnormalities were found to be statistically associated with a higher risk of death; low serum albumin; high serum bilirubin; prolonged prothrombin time; high serum creatinine; ascites, gastro- intestinal haemorrhage and encephalopathy on admission and during follow-up. Neither age nor sex significantly influenced survival, and continued alcohol abuse had little effect, though this may be because most patients drank little alcohol. Inflammatory activity in liver biopsy, liver size and spleen size did not affect prognosis. A multivariate analysis of the variables screened improved discrimination of a poor prognosis and permits calculation of a better prognotic index than a simple Child's grading. These will be compared in patients with alcoholic cirrhosis seen here in 1979. 54 AUGMENTED BILIARY LOSS OF PLASMAALBUMIN DURING BILE SALT CHOLERESIS IN DOGS - EVIDENCE FOR A CANALICULARESCAPEROUTE S.E. Bradley, K. Weigand, R. Preisi 9 Department of Clinical Pharmacology, University of Berne, Berne Switzerland In transfer from blood to bile, plasma proteins, other than IgA, appear to undergo mole- cular sieving consistent with passage by filtration across a semipermeable membrane. If this is so and if the hypothetical membrane is located at the canalicular level, increasing the osmotic pressure gradient within the canaliculi by bile salt (BS) loading should augment bil- iary albumin excretion without effect on IgA output which has been found to depend largely upon active transport and/or local synthesis. To test this hypothesis, the excretion of plasma albumin and IgA in the bile (Thomas cannula) of trained unanesthetized female dogs (n=12) was measured during choleresis produced by iv loading with sodium taurocholate. Simultaneous meas- urements of 3H-sucrose (Cs) and sodium 14C-ferrocyanide (Cf) or of 14C-carboxyl and 3H-methoxy- inulin (Cc,Ch) clearances (n=6 each) were made to define the local bioelectrical constraint upon anionic motion in terms of reduction of the clearance of the anionic species (Cf,Cc) rel- ative to that of its neutral size-matched comparator molecule (Cs,Ch).Plasma albumin (Alb) and ]gA were determined by two-dimensional immunodiffusion using monospecific antisera. BS output rose from 20.7+SD 9.1 to 44.4+4.0 nmol/min (p<.O01), and was associated with a regular and re- versible rise~n Alb output -[331+125 to 569+352 mg/min; p<.05, n=12) and choleresis (.19+.09 to .39+.09 ml/min, p<.O01). In c~trast, IgA-output remained unchanged (27+14 to 28+8% pITsma IgA). The Cc/Ch ratio decreased (.29+.07 to .19+.03, p<.05) whereas Cf/Cs ~id not c~ange con- sistently. These data are consistent--with entry--of Alb into the bile at the canalicular level presumably via the paracellular pathway and negatively charged channels that retard movement of molecules as large or larger than inulin. $27

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Page 1: Prognostic factors in alcoholic cirrhosis

53 PROGNOSTIC FACTORS IN ALCOHOLIC CIRRHOSIS

Bradbear R, Jenkins WJ, Ashby D*, Sherlock S. Depts of Medicine and Epidemiology*, Royal Free Hospital School of Medicine, Pond Street, London, NW3 2PF, UK.

To identify factors which'influence the life expectancy of patients with alcoholic cirrhosis we analysed survival data from 138 consecutive patients admitted to this hospital in 1980 and 1981. All patients were followed until death or until the end of the study in February 1984. Clinical, laboratory and histological variables which are routinely recorded were screened and the relative risk associated with each variable was calculated.

At the end of the study 67 patients were alive and 71 were dead. Only 17 deaths could not definitely be accounted for by complications of cirrhosis. The following abnormalities were found to be statistically associated with a higher risk of death; low serum albumin; high serum bilirubin; prolonged prothrombin time; high serum creatinine; ascites, gastro- intestinal haemorrhage and encephalopathy on admission and during follow-up. Neither age nor sex significantly influenced survival, and continued alcohol abuse had little effect, though this may be because most patients drank little alcohol. Inflammatory activity in liver biopsy, liver size and spleen size did not affect prognosis.

A multivariate analysis of the variables screened improved discrimination of a poor prognosis and permits calculation of a better prognotic index than a simple Child's grading. These will be compared in patients with alcoholic cirrhosis seen here in 1979.

54 AUGMENTED BILIARY LOSS OF PLASMA ALBUMIN DURING BILE SALT CHOLERESIS IN DOGS - EVIDENCE FOR A CANALICULAR ESCAPE ROUTE

S.E. Bradley, K. Weigand, R. Preisi 9

Department of Clinical Pharmacology, University of Berne, Berne Switzerland

In transfer from blood to bi le, plasma proteins, other than IgA, appear to undergo mole- cular sieving consistent with passage by f i l t r a t i o n across a semipermeable membrane. I f this is so and i f the hypothetical membrane is located at the canalicular level, increasing the osmotic pressure gradient within the canaliculi by bi le salt (BS) loading should augment b i l - iary albumin excretion without effect on IgA output which has been found to depend largely upon active transport and/or local synthesis. To test this hypothesis, the excretion of plasma albumin and IgA in the bi le (Thomas cannula) of trained unanesthetized female dogs (n=12) was measured during choleresis produced by iv loading with sodium taurocholate. Simultaneous meas- urements of 3H-sucrose (Cs) and sodium 14C-ferrocyanide (Cf) or of 14C-carboxyl and 3H-methoxy- inulin (Cc,Ch) clearances (n=6 each) were made to define the local bioelectrical constraint upon anionic motion in terms of reduction of the clearance of the anionic species (Cf,Cc) rel- ative to that of i ts neutral size-matched comparator molecule (Cs,Ch).Plasma albumin (Alb) and ]gA were determined by two-dimensional immunodiffusion using monospecific antisera. BS output rose from 20.7+SD 9.1 to 44.4+4.0 nmol/min (p<.O01), and was associated with a regular and re- versible r i se~n Alb output -[331+125 to 569+352 mg/min; p<.05, n=12) and choleresis (.19+.09 to .39+.09 ml/min, p<.O01). In c~t ras t , IgA-output remained unchanged (27+14 to 28+8% pITsma IgA). The Cc/Ch ratio decreased (.29+.07 to .19+.03, p<.05) whereas Cf/Cs ~id not c~ange con- sistently. These data are consistent--with entry--of Alb into the bile at the canalicular level presumably via the paracellular pathway and negatively charged channels that retard movement of molecules as large or larger than inul in.

$27