Download Serum lipoprotein (a) levels in liver diseases caused by

Indian J Med Res 120, December 2004, pp 542-545
Serum lipoprotein (a) levels in liver diseases caused by hepatitis
M. Irshad
Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of
Medical Sciences, New Delhi, India
Received November 6, 2003
Lipoprotein (a) [LP(a)] is a genetic variant of low density lipoprotein (LDL) and is mainly
synthesized in liver. We conducted a study to evaluate the association of serum [ Lp(a)] level with
hepatitis viral infections. A total of 130 patients including 50 patients with acute viral hepatitis
(AVH), 30 with chronic active hepatitis (CAH), 30 with cirrhosis of liver and 20 patients with
fulminant hepatic failure (FHF) were analysed for different hepatitis viral markers and Lp(a)
level in their serum samples. For comparison, 50 healthy persons were also tested for Lp(a) level.
Serum Lp(a) level in patients in all the disease groups was significantly reduced compared to
that observed in controls. Lp(a) level could not be detected in 40 per cent cases with AVH, 46.6
per cent with CAH, 70 per cent with cirrhosis and 80 per cent of FHF patients. On correlating
Lp(a) level to viral etiology in these patients, it was found that the extent of diminution in Lp(a)
level did not follow any trend with some particular viral infection and was recorded nearly same
in all the infections. The findings of this study suggested that serum Lp(a) level was significantly
(P<0.001) reduced in patients with liver diseases irrespective of the viral etiology.
Key words HBV - HCV - hepatitis - HEV
Lipoprotein (a) [Lp(a)] is a circulating particle
closely related to low density lipoprotein (LDL). It is
a genetic variant of LDL and consists of covalent
association of the unique and enigmatic apolipoprotein
(a) to apolipoprotein B-100 by a single disulphide
bridge1.
diabetes7 and liver and renal failure8-10 have strong
influence on Lp(a) levels in plasma, suggesting that
factors other than genetic may also play a central role in
the intricate metabolism of the lipoprotein.
It has been reported that raised Lp (a)
concentrations have relation with genesis , progression
and complications of both atherosclerosis and
thrombosis11. These findings caused an interest among
researchers to correlate serum/plasma Lp(a) level with
clinical informations and use this parameter to predict
the risk of cardiovascular or thrombotic diseases in
patients belonging to various other disease groups.
The metabolism of Lp(a), from synthesis to
catabolism is not clear. More than 90 per cent of Lp(a)
level is under genetic regulation and greater part is
accounted for by size polymorphism in the sequence of
apo(a) gene2. Besides, metabolic abnormalities, such as
the acute phase response 3,4 , hormone disorders 5,6,
542
IRSHAD: LP(a) IN VIRAL HEPATITIS
The present study was planned to quantitate Lp(a)
level in patients with various forms of liver diseases
caused by hepatitis viral infections to establish the
possible relationship between different viral infections
and circulating Lp(a) level.
A total of 130 adults patients of both sexes were
included in the present study. These included 50
patients (age range: 21-48 yr) with acute viral
hepatitis (AVH); 30 (age range: 19-48 yr) with chronic
active hepatitis (CAH), 30 (age range: 34-57 yr) with
cirrhosis of the liver, and 20 patients (age range: 2846 yr) with fulminant hepatic failure (FHF). These
patients attended either outpatient department or were
admitted to the liver unit of All India Institute of
Medical Sciences (AIIMS), New Delhi, during March
1999 to February 2002. They were evaluated
clinically and biochemically and their sera were tested
for hepatitis viral markers. The diagnosis of different
types of liver diseases was based on accepted clinical,
biochemical and histological criteria12,13. None of the
patients had a past history of alcohol intake or using
any drug. Fifty age and sex matched healthy
individuals were included as controls.
From each patient, 6-10 ml of venous blood was
drawn and aliquoted in plain tubes without
anticoagulant. Serum was separated after
centrifugation and then stored at -70 0C until further
analysed for hepatitis viral markers and Lp(a). Sera
were investigated for hepatitis B surface antigen
(HBsAg) and IgM antibodies to hepatitis A virus (IgM
anti-HAV), hepatitis B core antigen (IgM anti-HBc)
(kits from Abbot Laboratories, USA), hepatitis D
virus (IgM anti-HDV) (kit from Wellcome,UK) and
hepatitis E virus (IgM anti-HEV) (ELISA kit from
Genlabs & Diagnostics, Singapore). Similarly, all
these sera were also tested for total antibodies against
hepatitis C virus (anti-HCV) using highly sensitive
third generation ELISA kit from Ortho diagnostics,
UK.
543
Lp(a) level in serum samples was estimated by a
specific and sensitive immunoturbidimetric assay
where agglutination occurs due to an antigen-antibody
reaction between Lp(a) in a sample and anti-Lp(a)
antibody adsorbed to latex particles. This
agglutination is detected as an absorbance change at
700 nm proportional to the concentration of Lp(a) in
the sample. Lp(a) estimation was done on
autoanalyser Hitachi-917, Japan using test kits from
Randox laboratories, UK. The standards and control
samples to calibrate equipment for serum Lp(a) level
were also obtained from Randox Laboratories, UK.
The diagnosis of HAV infection was confirmed by
the presence of IgM anti-HAV in serum HBV by the
presence of IgM anti-HBc in sera of AVH and FHF
patients and by the persistent HBsAg antigenaemia
and/or presence of IgG anti-HBc in sera of CAH and
cirrhosis cases. Presence of IgM anti-HCV and IgM
anti-HDV in sera samples was used for the diagnosis
of HCV and recent HDV infections, respectively.
Active or recent HEV infection was diagnosed by the
presence of IgM anti- HEV in serum. Sera positive
for HBsAg but negative for all other viral markers
were labelled as HBV-carriers. Absence of all the
markers including HBsAg labelled the patients with
hepatitis non-ABCDE infection on exclusion criteria.
HAV and HDV infections were absent in all the
patients. AVH patients had hepatitis B infection in 10
cases, hepatitis C in 2 and hepatitis E in 16 patients,
respectively. Three patients had mixed BCE infection.
Four patients had no marker and were labelled as
hepatitis non- BCE cases; 15 patients were positive
for HBsAg only and labelled as HBV-carriers. CAH
patients had hepatitis B, C and mixed BC infection in
11, 7 and 7 patients, respectively. Five patients had
no marker and labelled as hepatitis non-BC cases. In
cirrhosis group, hepatitis B,C, mixed BC and nonBC were detected in 8, 6, 1 and 15 cases, respectively.
In FHF group , hepatitis B, C, E and mixed BCE
infection was recorded in 4, 7, 7 and 1 cases,
respectively. One patient was detected with non-BCE
infection and none was found to be the HBV-carrier.
544
INDIAN J MED RES, DECEMBER 2004
Table. Serum Lp(a) level in different liver diseases
Disease group
Acute viral hepatitis (AVH)
Chronic active hepatitis (CAH)
Cirrhosis of liver
Fulminant hepatic failure (FHF)
Healthy controls
Lp(a) level
(mg/dl)
7.4
10.3
6.7
10.2
15.4
±
±
±
±
±
15.3*
18.2*
12.9*
14.9*
13.1
* P<0.001 compared to control
Lp(a) level in all the patients with different liver
diseases, irrespective of viral etiology, was found to
be significantly diminished (P< 0.001) as compared
to controls. Interestingly, Lp(a) level was not detected
in 20 of 50 (40%) patients with AVH, 14 of 30 (46.6%)
patients with CAH, 21 of 30 (70%) with hepatic
cirrhosis, and 16 of 20 (80%) patients with FHF. Five
patients with AVH, who were followed up for six
months, showed an increasing level of serum Lp(a)
with recovery of the disease. The mean value of Lp(a)
observed in acute phase (9.2 ± 3.6 mg/dl) of these
five patients reached to 22.4 ± 4.0 mg/dl after six
months of recovery.
Lp(a) was first demonstrated by Berg in 196314
as a circulating particle which consists of
apolipoprotein B-100 linked to apolipoprotein (a) by
a disulphide bridge. Liver is the major source of
circulating Lp(a)15,16. This finding was also confirmed
by the observation that after liver transplantation,
the recipients acquired donors’ apo(a) phenotype17.
Subsequent studies reported that it is apo(a) and not
the total Lp(a) particle, which is secreted by the
hepatocyte18, and this apo(a) is extracellularly linked
to apo B-100 on liver cell surface19.
Some studies have described a possible relation
between Lp(a) and liver diseases. Geiss et al 20
demonstrated acute viral hepatitis with diminished
Lp(a) serum concentration. Valimaki et al21 reported
low Lp(a) in chronic liver diseases of different
etiology. Our study showed that both acute and chronic
liver diseases including cirrhosis of liver were
associated with diminished serum Lp(a)
concentrations. Lp(a) concentrations tended to be
reduced in high proportions in patients with more
severe forms of liver diseases like FHF and cirrhosis
of liver as compared to acute and chronic liver failure
(Table). Absence of detectable Lp(a) level in some
patients is in agreement with the findings of Feely et
al8 who could not detect Lp(a) level in patients with
hepatic cirrhosis. Since liver is the organ synthesising
Lp(a)16,17, reduced Lp(a) level during liver diseases
was supposed to result from its diminished synthesis
by the damaged liver. This view is also supported
by other studies8,22,23. Our data indicate that there is
an apparent decline in Lp(a) level in all types of
hepatitis viral infections. Though, reduction in Lp(a)
level does not appear to follow any trend in relation
to the causative hepatitis virus, it seems that reduction
in Lp(a) level is not dependent on the nature of
causative virus.
In conclusion, serum Lp(a) level in patients with
liver diseases induced by hepatitis viral infections was
significantly reduced compared to healthy controls.
Reduction in Lp(a) level appears to be independent of
causative hepatitis viral infection.
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Reprint requests: Dr M. Irshad, Additional Professor, Department of Laboratory Medicine,
All India Institute of Medical Sciences, New Delhi 110029, India
e-mail: [email protected]