Clinical Biochemistry in Hepatobiliary Diseases: Proceedings of the International Satellite Symposium, Bologna, Italy, 1988

200 Pages·1989·7.23 MB·English

by  I. W. Percy-Robb (auth.)

Progress in
8
Clinical Biochemistry
and Medicine
Clinical Biochemistry in
Hepatobiliary Diseases
Editors:
F. Salvatore, A. Roda, L. Sacchetti
Proceedings of the International Satellite
Symposium, Bologna, Italy, 1988
With Contributions by
C. Armanino, Y Artur, N. Blanckaert, G. Castaldo,
D. Festi, 1. Fevery, M. M. Galteau, 1. Griffiths,
A. Minutello, D.W Moss, M. Muraca, LW Percy-Robb,
R. Rizzoli, A. Roda, E. Roda, S. B. Rosalki,
L. Sacchetti, E Salvatore, G.1. Sanderink, E Schiele,
G. Siest, P. Simoni, E Vanstapel, M. Wellman,
M.Wemer
With 72 Figures
Springer-Verlag Berlin Heidelberg NewY ork
London Paris Tokyo Hong Kong
Guest Editors
Prof. Francesco Salvatore
Dipartimento di Biochimica e Biotecnologie Mediche, Universita
di Napoli, II Facolta di Medicina, Via S. Pansini, 5, 1-80131 Napoli/
Italy
Prof. AIdo Roda
Istituto di Chimica Analitica, Universita di Messinajltaly
Prof. Lucia Sacchetti
Dipartimento di Biochimica e Biotecnologie Mediche, Universita
di Napoli, II Facolta di Medicina, Via S. Pansini, 5, 1-80131 Napoli/
Italy
ISBN-13: 978-3-642-74396-2 e-ISBN-13: 978-3-642-74394-8
DOl: 10.1007/978-3-642-74394-8
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© Springer-Verlag Berlin Heidelberg 1989
Softcover reprint of the hardcover I st edition 1989
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Editorial Board
Prof Dr. Etienne Baulieu Universite de Paris Sud, Departement de Chimie
Biologique, Faculte de Medecine de Bicetre,
Hopital de Bicetre, F-94270 Bicetre/France
Prof Dr. Donald T. Forman Department of Pathology, School of Medicine,
University of North Carolina
Chapel Hill, NC 27514/USA
Prof Dr. Magnus Karolinska Institutet, Institutionen for
Ingeltnan-Sundberg Medicinsk Kemi, Box 60400
S-10401 Stockholm/Sweden
Prof Dr. Lothar Jaenicke Universitiit Koln, Institut fiir Biochemie
An der Bottmiihle 2
D-5OO0 Koln I/FRG
Prof Dr. John A. Kellen Sunnybrook Medical Centre, University
of Toronto, 2075 Bayview Avenue
Toronto, Ontario, Canada M4N 3M5
Prof Dr. Yoshitaka Nagai Department of Biochemistry, Faculty
of Medicine, The University of Tokyo
Bunkyo-Ku, Tokyo/Japan
Prof Dr. Georg F. Springer IlJlmunochemistry Research, Evanston Hospital
Northwestern University, 2650 Ridge Avenue,
Evanston, IL 60201/USA
Prof Dr. Lothar Trager Klinikum der Johann Wolfgang Goethe
Universitiit, Gustav-Embden-Zentrum
Theodor Stem Kai 7
D-6000 Frankfurt a. M. 70/FRG
Prof Dr. Liane Will-Shahab Akademie der Wissenschaften der DDR
Zentralinstitut fUr Herz-und Kreislauf-Forschung
Lindenberger Weg 70
DDR-1115 Berlin-Buch
Prof Dr. Jatnes L. Wittliff Hormone Receptor Laboratory, James Graham
Brown Cancer Center, University of Louisville
Louisville, KY 40292/USA
Preface
The clinical biochemistry ofhepatobiliary diseases is very widely studied, and publica
tions abound on this topic. However, there is no recent publication that provides a
comprehensive collection of the various leading aspects that go to make up this
complex theme. Therefore, we thought it useful to gather together a few scientists
whose work has focused on the various clinical biochemistry-aspects of these disorders
in order that they might discuss their experience and expertise.
The aim of the International Satellite Symposium on Clinical Biochemistry in
Hepatobiliary Disease, in addition to reviewing the individual aspects, was to
describe the state-of-the-art so as to provide useful data for laboratory scientists and
also for physicians working in the field of hepatobiliary diseases, and these two aims
are clearly reflected in the chapters of this volume.
The volume opens with an introductory chapter that gives a general overview of
the various aspects of the clinical biochemistry of these disorders, while the closing
chapter deals with an important aspect that deserves to be increasingly emphasized
in laboratory medicine, i.e., strategies to integrate information coming from the
laboratory to make them more useful for clinical diagnosis.
Despite the widespread use of biochemical tests in hepatobiliary diseases, they
are still unable to provide_ a key with which to decipher the biochemical characteristics
of these disorders. The five chapters in this book devoted to clinical enzymology go
some way to giving an insight that may provide such a key. One of these chapters
concerns a biochemical signal, the serum gamma-glutamyltransferase pattern, which
is slowly emerging from the clinical enzymology of hepatic diseases and that might
contribute to discriminating between various hepatobiliary disorders. Two chapters
are devoted to alkaline phosphatase, one to amylase and another to specific
enzymatic systems that are particularly involved in hepatic diseases. This has been
an extremely fruitful area over the past few years, and these four chapters admirably
review the progress made and provide indications regarding the directions in which
this field will develop in the future.
One of the remaining two papers deals with particular aspects of the clinical
biochemistry of hepatobiliary diseases that are involved in the metabolism of biliary
pigments, particularly bilirubins. This topic has received much attention in the past;
however, the advancements made in recent years have transformed the field, and
Dr. Blanckaert and coworkers have provided a lucid update of the present situation.
Lastly, there is the chapter devoted to cholesterol catabolism, particularly as regards
bile acids. Here Professor Roda and his group give an extensive overview of both
the chemical-physical and clinical aspects of bile acid analysis in biological fluids.
VIII Preface
We would like to end this brief preface by thanking Jean Gilder for having
revised and edited the papers where necessary and for having compiled the subject
index. In addition, we are most indebted to Boehringer Biochernia Robin (Italy) for
their generous support of this symposium.
Italy, February 1989 Francesco Salvatore, MD, Ph.D
Aldo Roda, Ph.D.
Lucia Sacchetti, Ph.D.
Table. of Contents
The Clinical Biochemistry of Hepatobiliary Diseases
I. W. Percy-Robb. . . . . . . . . . . '. . . .
The Serum Garnma-glutamyltransferase Isoenzyme System
and its Diagnostic Role in Hepatobiliary Disease
L. Sacchetti, G. Castaldo, F. Salvatore. . . . . . . . . 17
Alkaline Phosphatase in Hepatobiliary Disease
D. W. Moss .............. . 47
Enzymatic Profiles of Hepatic Disease Investigated
by Alkaline Phosphatase Isoenzymes and Isoforms
J. Griffiths. . . . . . . . . . . . . . . . . . 63
Reference Values and Drug Effects on Hepatic Enzymes
Y. Artur, G. Siest, G. J, Sanderink, M. Wellman, M, M. Galteau,
F. Schiele .................... . 75
Plasma Amylase in Pancreatic and Hepatobiliary Disease
S. B. Rosalki ... . . . . . . . . . . . . . . . . . . 93
Clinical Significance of Recent Developments in Serum Bilirubins
N. Blanckaert, J. Fevery, F. Vanstapel, M. Muraca . . . . . . . 105
Methodological and Clinical Aspects of Bile Acid Analysis in Biological Fluids
A. Roda, D. Festi, C. Armanino, R. Rizzoli, P. Simoni, A. Minutello,
E. Roda . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
Strategies to Integrate Laboratory Information into the Clinical Diagnosis
of Hepatic and Acute Pancreatic Disease
M. Werner. . . . . . . . 175
Author Index Volumes 1-8 . 187
Subject Index. . . . . . . 189
The Clinical Biochemistry of Hepatobiliary
Diseases
~. w. Percy-Robb
Professor in Pathological Biochemistry, Department of Pathological Biochemistry,
Western Infirmary, Glasgow GIl 6NT, UK
Biochemical tests of liver function are a part of the routine investigation of patients who give a history
which suggests that liver disease is present.
The transport function of the liver is usually assessed by measurements of total bilirubin
concentration in the patient's plasma. The enterohepatic circulation of bile acids provides an
endogenous background against which transport can be assessed, the molar ratio of bile acids to
bilirubin traversing the liver being about 150: I.
The integrity of hepatic parenchymal cells is most commonly assessed by measurements of the
activities of the aminotransferase enzymes in serum. Using radioimmunoassay, mass measurements
of the glutathione transferase are available and may show rises in liver disease. These enzymes represent
about 5 % of the total cytosolic protein in hepatic parenchymal cells and it appears that these
immunoassay measurements can provide an extremely sensitive liver function test.
Liver biopsy is both invasive and not without risk to the patient. Measurements of proc ollagen III
peptide may provide a non-invasive method for assessing hepatic fibrosis in alcoholic liver disease and
cirrhosis.
The use of bile acid measurements and of high performance liquid chromatography of bilirubin
in assessing hepatic transport, of mass measurements of the glutathione transferase, and of procollagen
III peptide is reviewed.
I Introduction. . . . . . . . . . . . . . . 2
2 Bilirubin and Bile Acid Measurements. . . . 3
2.1 Background Physiological Considerations 3
2.2 Methods of Bile Acid Measurement in Plasma. 5
2.3 Bile Acid Measurements in Chronic Liver Disease and Terminal Ileal Disease . 5
2.4 Bile Acid Measurements in Mild Hyperbilirubinaemia. . . . . . . . 5
2.5 HPLC Assessment of Conjugated/Unconjugated Bilirubin . .. . . . 7
3 Clinical Biochemistry and the Glutathione-S-transferase Enzymes (GST) . 9
3.1 GST in Paracetamol Overdose . . . . . 9
3.2 GST in Alcoholic Cirrhosis. . . . . . . 11
4 Procollagen III Peptide and Hepatic Fibrosis. 11
5 References. . . . . . . . . . . . . . . . 14
Progress in Clinical Biochemistry
and Medicine, Vol. 8
© Springer·V erlag Berlin Heidelberg 1989
2 I. W. Percy-Robb
1 Introduction
The clinical investigation of patients suspected of having liver disease, or in whom
liver disease has previously been established, is based on a complex matrix of data
which include not only a carefully taken case history and full clinical examination
but in most cases also depends on laboratory tests as well as ultrasound and radiological
investigations. The principal aims of this approach are I) to detect whether liver
disease is present, 2) to make a differential diagnosis of the type of liver disease
present, 3) to assess the severity of the disease, 4) to follow the progress of the
disease and where possible, 5) to assess the likely prognosis. In addition to these
laboratory and radiological and ultrasound investigations, the diagnosis in a propor
tion of cases rests on histological examination of tissue taken at biopsy.
Biochemical tests are used to assess the structural integrity of the liver, its
ability to transport substances from the blood' into bile and its ability to synthesise
and secrete substances into the blood. Many tests of these functions have been
advocated, but in clinical practice only a few have proved both informative and
feasible to perform on a large scale. The most widely used combination includes
the serum total bilirubin concentration as an index of hepatic transport function
and of the severity of clinical jaundice, the serum transaminase activity as a measure
of the integrity of hepatic parenchymal cells, the serum alkaline phosphatase activity
as an index cholestasis and the serum albumin concentration as a measure of hepatic
synthetic capacity. Collectively this group of tests are known as "the liver function
tests" even though they do not all measure hepatic function. They should, however,
not be considered to be routine but rather should be used only when there is some
reason to suspect hepatic disorder.
In addition to these widely used tests, the prothrombin time is sometimes used
as a test of hepatic synthetic function because it depends on coagulation factors
that are synthesised in the liver and the serum globulin concentration may be helpful
in assessing the severity of chronic liver disease. A specific set of biochemical
tests may be used to detect specific diseases. These include serum alpha-fetoprotein,
alpha-I-antitrypsin and ceruloplasmin.
Collectively these biochemical investigations are now widely used and it is not
the purpose of this chapter to review their use in detail. Rather, I wish to consider
some aspects of three types of investigation which may prove to be useful additional
biochemical investigations in patients with liver disease. These are I) the use of
fractionated bilirubin measurements and bile acid measurements especially in the
assessment of patients with mild, anicteric hyperbilirubinaemia, 2) the use of
immunoassay measurements of the hepatic glutathione-S-transferase enzymes in
plasma and 3) the measurement of the procollagen-Ill-peptide in plasma which may
provide a non-invasive method for assessing hepatic fibrosis in alcoholic liver disease
and in hepatic cirrhosis.
The Clinical Biochemistry of Hepatobiliary Diseases 3
2 Bilirubin and Bile Acid Measurements
2.1 Background Physiological Considerations
One of the commonly recognised clinical features of liver disease is the presence
of jaundice. The yellow tinge to sclera and skin leads naturally to clinical curiosity
about the plasma bilirubin concentration which has become one of the main
components of the group of investigations which together constitute the liver function
tests. Bilirubin is transported in the plasma mainly in a reversibly bound form
with albumin, its uptake by the liver apparently being carrier mediated. Conjugation
of bilirubin at the surface of the endoplasmic reticulum is enzymatic and i~followed
by excretion of mainly mono-and di-glucuronides of bilirubin in bile. Once secretion
of bilirubin conjugates by the biliary tree is completed there is no significant
reabsorption of bilirubin from the gut. Bilirubin concentrations in plasma therefore
represent the algebraic sum of the rates of entry of bilirubin into the plasma space
and of its exit by way of the hepatic uptake process.
Bile acids, on the other hand, are subjected to a rather dynamic enterohepatic
circulation, which depends on bile acid secretion by the liver, followed by uptake from
Systemic _ Urinary
11 jLmol/ 24 h l
/ circulation excretion
I
I
\
f
Faecal
excretion
(1mmol/24hl
Fig. 1. Diagramatic representation of the enterohepatic circulation of the bile acids in man