Scandinavian Journal of Clinical and Laboratory Investigation
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Serum Concentrations and Excretion of Bile Acids in Cirrhosis G. Jönsson, G. Hedenborg, O. Wisén & A. Norman To cite this article: G. Jönsson, G. Hedenborg, O. Wisén & A. Norman (1992) Serum Concentrations and Excretion of Bile Acids in Cirrhosis, Scandinavian Journal of Clinical and Laboratory Investigation, 52:7, 599-605, DOI: 10.1080/00365519209115502 To link to this article: http://dx.doi.org/10.1080/00365519209115502
Published online: 29 Mar 2011.
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Date: 23 April 2016, At: 01:38
Scand J Clin Lab Invest 1992; 52: 599-605
Serum concentrations and excretion of bile acids in cirrhosis G. JONSSON, G. HEDENBORG, 0.WISEN & A. NORMAN
Downloaded by [New York University] at 01:38 23 April 2016
Department of Clinical Chemistry, Karolinska Hospital and Department of Clinical Alcohol and Drug Addiction Research, Kardinska Hospital, S-104 01 Stockholm, Sweden
Jonsson G, Hedenborg G, Wisen 0, Norman A. Serum concentrations and excretion of bile acids in cirrhosis. Scand J Clin Lab Invest 1992; 52: 599-605. Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients.with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (=synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.
Key words: bile acids and salts; liver cirrhosis. alcoholic; urine; faeces Gerd Jonsson, Department of Clinical Chemistry, Karolinska Hospital, S-104 01 Stockholm, Sweden.
In liver cirrhosis, several changes in bile acid metabolism and transport occur. Serum bile acid concentrations increase, which has been attributed to less efficient extraction and transport of bile acids by the hepatocytes, or a result of internal hepatic and porto-systemic shunts of blood flow [l]. As a consequence of increased serum bile acid concentrations, the urinary excretion of bile acids also increases [21. The synthesis of bile acids is considered to be
decreased in severe liver disease [3], and the synthesis of chenodeoxycholic acid (CDC) from cholesterol is favoured compared to that of cholic acid (C), which may result in a lower C:CDC ratio in serum in patients with liver cirrhosis [4]. In the present study, samples from ten patients with liver cirrhosis were collected for qualitative and quantitative determination of individual bile acids. Eight patients with cir599
Downloaded by [New York University] at 01:38 23 April 2016
600
G. Jiinsson et al.
rhosis, but without serious hepatic decompensation (Child group A), were chosen to represent early changes in bile acid metabolism and were studied together with two additional patients with end-stage disease (Child group C). The aims of the study were to examine bile acid synthesis in liver cirrhosis, measured as total daily excretion of bile acids, and to study the relationship between serum bile acidconcentration and other parameters of cholestasis in such disease. Furthermore, the variations with time in serum bile acid-concentrations and bile acid-excretion in patients with liver disease were studied. The nature of bile acids in these patients is described in a preceding paper 151.
standing alcohol abuse, and had clinical signs and laboratory data indicative of liver disease. In all patients, the diagnosis of liver cirrhosis was verified by percutaneous liver biopsy. The renal function was normal in all patients as evaluated from serum creatinine concentrations. At the time of the study, all patients had abstained from alcohol for more than one month. The clinical status of the patients was categorized as described by Child [61, and the Child index was calculated as modified by Campbell et al. [7]. Clinical and laboratory data of the patients are given in Table I. The majority of the patients were Child's group A , indicating that liver function was only mildly impaired. A t the time of the study, the patients were in a steady state. Patient 1 was hospitalized due to liver failure with mild encephalopathy during the study. The remainder of the patients were outpatients, and the samples for the study were collected in connection with regular sampling for liver function tests before followup visits at the clinic.
MATERIALS A N D METHODS Patients Ten patients with liver cirrhosis participated in the study. All patients had a history of long-
TABLE I . Clinical and laboratory data of the patients studied Pat icnt 1
Clinicul dutu Sex Age Weight Height Child's index"' Medication"' Ascites Luborutory d u d " (reference values) S-Bilirubin ( 70'%) S-Aspartate amino-transfcrase ( 4 . 7 0 pkat I-') S-Alanine amino-transferase (41.70 pkat I-') (
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Serum Concentrations and Excretion of Bile Acids in Cirrhosis G. Jönsson, G. Hedenborg, O. Wisén & A. Norman To cite this article: G. Jönsson, G. Hedenborg, O. Wisén & A. Norman (1992) Serum Concentrations and Excretion of Bile Acids in Cirrhosis, Scandinavian Journal of Clinical and Laboratory Investigation, 52:7, 599-605, DOI: 10.1080/00365519209115502 To link to this article: http://dx.doi.org/10.1080/00365519209115502
Published online: 29 Mar 2011.
Submit your article to this journal
Article views: 7
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iclb20 Download by: [New York University]
Date: 23 April 2016, At: 01:38
Scand J Clin Lab Invest 1992; 52: 599-605
Serum concentrations and excretion of bile acids in cirrhosis G. JONSSON, G. HEDENBORG, 0.WISEN & A. NORMAN
Downloaded by [New York University] at 01:38 23 April 2016
Department of Clinical Chemistry, Karolinska Hospital and Department of Clinical Alcohol and Drug Addiction Research, Kardinska Hospital, S-104 01 Stockholm, Sweden
Jonsson G, Hedenborg G, Wisen 0, Norman A. Serum concentrations and excretion of bile acids in cirrhosis. Scand J Clin Lab Invest 1992; 52: 599-605. Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients.with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (=synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.
Key words: bile acids and salts; liver cirrhosis. alcoholic; urine; faeces Gerd Jonsson, Department of Clinical Chemistry, Karolinska Hospital, S-104 01 Stockholm, Sweden.
In liver cirrhosis, several changes in bile acid metabolism and transport occur. Serum bile acid concentrations increase, which has been attributed to less efficient extraction and transport of bile acids by the hepatocytes, or a result of internal hepatic and porto-systemic shunts of blood flow [l]. As a consequence of increased serum bile acid concentrations, the urinary excretion of bile acids also increases [21. The synthesis of bile acids is considered to be
decreased in severe liver disease [3], and the synthesis of chenodeoxycholic acid (CDC) from cholesterol is favoured compared to that of cholic acid (C), which may result in a lower C:CDC ratio in serum in patients with liver cirrhosis [4]. In the present study, samples from ten patients with liver cirrhosis were collected for qualitative and quantitative determination of individual bile acids. Eight patients with cir599
Downloaded by [New York University] at 01:38 23 April 2016
600
G. Jiinsson et al.
rhosis, but without serious hepatic decompensation (Child group A), were chosen to represent early changes in bile acid metabolism and were studied together with two additional patients with end-stage disease (Child group C). The aims of the study were to examine bile acid synthesis in liver cirrhosis, measured as total daily excretion of bile acids, and to study the relationship between serum bile acidconcentration and other parameters of cholestasis in such disease. Furthermore, the variations with time in serum bile acid-concentrations and bile acid-excretion in patients with liver disease were studied. The nature of bile acids in these patients is described in a preceding paper 151.
standing alcohol abuse, and had clinical signs and laboratory data indicative of liver disease. In all patients, the diagnosis of liver cirrhosis was verified by percutaneous liver biopsy. The renal function was normal in all patients as evaluated from serum creatinine concentrations. At the time of the study, all patients had abstained from alcohol for more than one month. The clinical status of the patients was categorized as described by Child [61, and the Child index was calculated as modified by Campbell et al. [7]. Clinical and laboratory data of the patients are given in Table I. The majority of the patients were Child's group A , indicating that liver function was only mildly impaired. A t the time of the study, the patients were in a steady state. Patient 1 was hospitalized due to liver failure with mild encephalopathy during the study. The remainder of the patients were outpatients, and the samples for the study were collected in connection with regular sampling for liver function tests before followup visits at the clinic.
MATERIALS A N D METHODS Patients Ten patients with liver cirrhosis participated in the study. All patients had a history of long-
TABLE I . Clinical and laboratory data of the patients studied Pat icnt 1
Clinicul dutu Sex Age Weight Height Child's index"' Medication"' Ascites Luborutory d u d " (reference values) S-Bilirubin ( 70'%) S-Aspartate amino-transfcrase ( 4 . 7 0 pkat I-') S-Alanine amino-transferase (41.70 pkat I-') (
