41
CIinica Chimico Acta, 85 (1978) 41-47 0 Elsevier/North-Holland Biomedical Press
CCA 9201
LIPOPROTEIN-X AND DIAGNOSIS OF CHOLESTASIS: COMPARISON WITH OTHER BIOCHEMICAL PARAMETERS AND LIVER BIOPSY
R. FELLIN
*, E. MANZATO,
S. ZOTTI
**, G. BAGGIO,
G. BRIAN1
and M. RUGGE
Department of Internal Medicine, Division of Gerontology and Metabolic University Hospital, Via Giustiniani 2, 35100 Padova (Italy) (Received
September
22nd,
***
Diseases,
1977)
summary The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative in 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in y-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-x formation and the possible relationships between LP-X and gammaglutamyl transpeptidase.
Introduction It is well known that patients with cholestatic liver disease commonly present elevated levels of serum free cholesterol and phospholipids [ 1,2]. Several reports have revealed that this increase in lipid levels is contemporaneous to the appearance of a low density lipoprotein of abnormal composition and properties, called lipoprotein-X (LP-X) [ 3-61. * To whom correspondence should be addressed. * * Present address: 3rd Medical Division, Padova City Hospital. *** Present address: Department of Pathology, University of Padova.
42
An important feature of this particular lipoprotein is its mobility toward the cathode in agar electrophoresis, easily visualized by polyanion precipitation or by immunological means [ 7 $1. The determination of the presence of LP-X, therefore, represents a new diagnostic test in the differential diagnosis of liver diseases. Several studies in adults and children [g--13] have demonstrated that the presence of this lipoprotein is highly specific for cholestasis, with the sole exception of a rare familial disease, lecithin-cholesterol-acyltransferase deficiency [ 141. Recently it has been shown that LP-X formation occurs when the Iipidprotein complex, normally excreted with the bile, refluxes into the plasma stream [15]. It has been observed that modifications in concentration and stability of LP-X are related to the severity of cholestasis and to the albumin/bile salts ratio in the plasma [ 161. The aim of this work was to evaluate the incidence of LP-X in various liver diseases and the relationship between this parameter and histological signs of cholestasis and other liver function tests. Materials
and methods
One hundred and fifty seven (106 males and 51 females) liver patients ranging in age between 16 and 70 years were studied. Some of these were admitted to the Department of Internal Medicine of the University of Padova and others to the 3rd Medical Division of Padova City Hospital. The diagnosis of hepatopathy was made on the basis of clinical data, liver function tests, X-rays, liver biopsy and in a third of the cases of explorative laparoscopy. The patients were divided into various groups on the basis of clinical diagnosis (Table I). The group with chronic hepatitis included both the persistent and the active forms. The miscellaneous group was made up of patients affected with different diseases in whom evidence of liver involvement had been confirmed: hepatic cancer with cirrhosis (3), metastasis to the liver (4), fatty liver (4), nonoccluding gallstones (S), chronic lymphocytic leukemia (l), chronic myelocytic leukemia (l), congestive hepatomegaly (4), granulomatous hepatitis (l), porphyria cutanea tarda symptomatica (3). All the patients underwent the following examinations: total bilirubin (TB); TABLE
I
CASE
REPORTS
SUBDIVIDED
ACCORDING
TO
DIFFERENT
__ Liver
disease
Liver
cirrhosis
Chronic Acute
22
hepatitis
2
liver
disease
cirrhosis
Extrahepatic Miscellaneous Total
of patients
65
hepatitis
Alcoholic Biliary
No.
biliary
23 3
obstruction
13 29 157
LIVER
DISEASES
43
protein electrophoresis; alkaline phosphatase (AP); gamma-glutamyl transpeptidase (y-GT); omithine carbamoyltransferase (OCT); glutamic-pyruvic transaminase (SGPT); glutamic-oxaloacetic transaminase (SGOT); prothrombin time; bromsulphalein test (BSP) and LP-X test. Percutaneous needle biopsy of the liver was carried out in two thirds of these cases while in one third liver biopsy was performed during explorative laparoscopy. The determination of SGPT (normal value
CIinica Chimico Acta, 85 (1978) 41-47 0 Elsevier/North-Holland Biomedical Press
CCA 9201
LIPOPROTEIN-X AND DIAGNOSIS OF CHOLESTASIS: COMPARISON WITH OTHER BIOCHEMICAL PARAMETERS AND LIVER BIOPSY
R. FELLIN
*, E. MANZATO,
S. ZOTTI
**, G. BAGGIO,
G. BRIAN1
and M. RUGGE
Department of Internal Medicine, Division of Gerontology and Metabolic University Hospital, Via Giustiniani 2, 35100 Padova (Italy) (Received
September
22nd,
***
Diseases,
1977)
summary The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative in 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in y-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-x formation and the possible relationships between LP-X and gammaglutamyl transpeptidase.
Introduction It is well known that patients with cholestatic liver disease commonly present elevated levels of serum free cholesterol and phospholipids [ 1,2]. Several reports have revealed that this increase in lipid levels is contemporaneous to the appearance of a low density lipoprotein of abnormal composition and properties, called lipoprotein-X (LP-X) [ 3-61. * To whom correspondence should be addressed. * * Present address: 3rd Medical Division, Padova City Hospital. *** Present address: Department of Pathology, University of Padova.
42
An important feature of this particular lipoprotein is its mobility toward the cathode in agar electrophoresis, easily visualized by polyanion precipitation or by immunological means [ 7 $1. The determination of the presence of LP-X, therefore, represents a new diagnostic test in the differential diagnosis of liver diseases. Several studies in adults and children [g--13] have demonstrated that the presence of this lipoprotein is highly specific for cholestasis, with the sole exception of a rare familial disease, lecithin-cholesterol-acyltransferase deficiency [ 141. Recently it has been shown that LP-X formation occurs when the Iipidprotein complex, normally excreted with the bile, refluxes into the plasma stream [15]. It has been observed that modifications in concentration and stability of LP-X are related to the severity of cholestasis and to the albumin/bile salts ratio in the plasma [ 161. The aim of this work was to evaluate the incidence of LP-X in various liver diseases and the relationship between this parameter and histological signs of cholestasis and other liver function tests. Materials
and methods
One hundred and fifty seven (106 males and 51 females) liver patients ranging in age between 16 and 70 years were studied. Some of these were admitted to the Department of Internal Medicine of the University of Padova and others to the 3rd Medical Division of Padova City Hospital. The diagnosis of hepatopathy was made on the basis of clinical data, liver function tests, X-rays, liver biopsy and in a third of the cases of explorative laparoscopy. The patients were divided into various groups on the basis of clinical diagnosis (Table I). The group with chronic hepatitis included both the persistent and the active forms. The miscellaneous group was made up of patients affected with different diseases in whom evidence of liver involvement had been confirmed: hepatic cancer with cirrhosis (3), metastasis to the liver (4), fatty liver (4), nonoccluding gallstones (S), chronic lymphocytic leukemia (l), chronic myelocytic leukemia (l), congestive hepatomegaly (4), granulomatous hepatitis (l), porphyria cutanea tarda symptomatica (3). All the patients underwent the following examinations: total bilirubin (TB); TABLE
I
CASE
REPORTS
SUBDIVIDED
ACCORDING
TO
DIFFERENT
__ Liver
disease
Liver
cirrhosis
Chronic Acute
22
hepatitis
2
liver
disease
cirrhosis
Extrahepatic Miscellaneous Total
of patients
65
hepatitis
Alcoholic Biliary
No.
biliary
23 3
obstruction
13 29 157
LIVER
DISEASES
43
protein electrophoresis; alkaline phosphatase (AP); gamma-glutamyl transpeptidase (y-GT); omithine carbamoyltransferase (OCT); glutamic-pyruvic transaminase (SGPT); glutamic-oxaloacetic transaminase (SGOT); prothrombin time; bromsulphalein test (BSP) and LP-X test. Percutaneous needle biopsy of the liver was carried out in two thirds of these cases while in one third liver biopsy was performed during explorative laparoscopy. The determination of SGPT (normal value
