74 Indian Medical Gazette — FEBRUARY 2013

Clinical Study

Study of Zinc in Cirrhosis of Liver

Kaushik Kar, Assistant Professor,
Gorachand Bhattyacharya, Professor
— Department of Biochemistry, Calcutta National Medical College, Kolkata.
Jayanta De, Professor and HOD,
Department of Biochemistry, Midnapore Medical College, Midnapore.

Abstract attention to this important and ever increasing cause of

73 liver cirrhosis patients have been selected. Serum
zinc and albumin levels were estimated in them in
comparison to controls. Significant decrease in zinc and
albumin levels were observed in liver cirrhosis patients.
This work is an attempt to understand the important role
that the zinc plays in the pathogenesis and therapy of liver
cirrhosis and the role of albumin in zinc transport.
Keywords
cirrhosis of liver, zinc, albumin
Introduction
Cirrhosis is defined anatomically as a diffuse process
of fibrosis and nodule formation due to different causes1.
Cirrhosis is elucidated histopathologically and has a variety
of clinical manifestations and complications, some of which
can be life threatening. Fibrosis and regenerative nodule
formation result in a decrease of hepatocellular mass,
function and alteration of blood flow. Induction of fibrosis
occurs with activation of hepatic stellate cells, resulting in
the formation of increased amount of collagen and other
components of extracellular matrix2.
From 1934 to 1964, Cirrhosis of liver was a leading
cause of death in United States. An increment in mortality
was close to 60%.Yet epidemiologists have paid very little
Address for correspondence: Dr Kaushik Kar, CE 184, Salt Lake City, Sector 1, Kolkata – 700 064. E-mail : kaushikkar37@yahoo.com
death3.
In India, several studies have shown that the two major
causative factors of cirrhosis are viral hepatitis and alcohol
abuse4.
Chronic hepatitis B (CHB) is an important global health
problem, with more than 350 million individuals affected
worldwide. Its prevalence in India is quite high. More than
1,000,000 Indian children run a lifetime risk of becoming
chronic carriers and about 100,000 Indians die from HBV
complications annually. During the course of hepatitis B
virus (HBV) infection, an estimated 15-40% of CHB patients
would develop complications such as acute exacerbation,
liver cirrhosis and hepatocellular carcinoma (HCC)5.
It has been observed that Hepatitis B Virus (HBV) is the
commonest cause of chronic liver disease in eastern India.
Alcohol and Hepatitis C Virus (HCV) are uncommon in this
part of the country6.
The study was carried out in the eastern part of India.
Majority of the study population are not well nourished
and may have micronutrient deficiency.
Zinc is second to iron as the most abundant trace
element in the body7. Symptoms of acute zinc deficiency
(anorexia, dysfunction of smell and taste and mental and
Indian Medical Gazette — FEBRUARY 2013 75

cerebellar disturbances) and chronic zinc deficiency Table 1 and Fig. 1 showed significant fall in (s) zinc
(growth retardation, anemia, testicular atrophy and impaired concentrations in liver cirrhosis patients, Table 2 and
wound healing) are common in cirrhosis patients. It remains Fig. 2 showed significant fall in (s) albumin levels in liver
unresolved whether these low serum zinc concentrations cirrhosis patients.
in these disease states are indicative of true symptomatic
or asymptomatic zinc deficiency, or merely reflect a
decrease in available zinc binding proteins, as well over
90% of serum zinc is bound to protein in normal subjects8.
Considering the fact, an attempt have been made to asses
the zinc level in cirrhotic patients with an object to establish
a correlation between zinc deficiency and manifestations
of cirrhosis of liver.

Albumin is the major plasma carrier of zinc, and the

amount of zinc transported in the blood depends not on
zinc but also on the availability of albumin9.
Fig. 1
In this study, we tried to asses the serum zinc as well Shows the serum zinc levels in controls and
as serum albumin levels in liver cirrhosis patients. liver cirrhosis patients

Materials and Methods

The study was conducted in the department of Bio-
chemistry, Calcutta National Medical College & Hospital,
Kolkata, West Bengal. Liver cirrhosis patients were collected
from outpatient department and wards of General Medicine
department of the hospital.73 cirrhosis patients, 42 males
and 31 females, age group of 30-60 years as well as 35
normal control subjects (age and sex matched) were selected
in the study. Diagnosis of cirrhosis was based on the Clinical,
Laboratory and Radiological criteria.

Cirrhosis associated with concomitant pathology like

diabetes mellitus, hypertension and renal failure were
excluded from the study. Severly ill,unconscious, disabled
and non co-operative patients were also excluded from the
study.

Fasting blood was collected and serum was separated

within optimum timing. Serum zinc and albumin was
analysed immediately. (S) Zinc was estimated by
colorimetric method. (Crest Biosystems)10. (S) Albumin was
estimated by Bromocresol green (BCG) dye binding method
(Crest Biosystems)11.
Discussion
Observations
Biochemical alterations in cirrhosis :
The results were tabulated and expressed as mean and
standard deviation. The data were compared by SPSS The transformation of normal liver to fibrotic liver and
software for significance. eventually cirrhosis is a complex process involving several
76
Fig. 2
Shows serum Albumin levels in controls and
liver cirrhosis patients
key components in particular stellate cells, cytokines, and
proteinases and their inhibitors. There is interaction between
stellate cells and adjacent sinusoidal and parenchymal cells,
cytokines and growth factors, proteases and their inhibitors,
and the extracellular matrix. The formation of fibrous tissue
depends not only on the synthesis of excess matrix but
also changes in its removal. This depends upon the balance
between enzymes that degrades the matrix and their
inhibitors.
Normal liver has a connective tissue matrix which
includes type IV collagen (non fibrillary), glycoproteins
(including fibronectin and laminin) and proteoglycans
(including heparin sulphate). These comprise the low density
basement membrane in the space of Disse. Following hepatic
injury there is a three to eightfold increase in the extracellular
matrix, which is of a high density interstitial type, containing
fibril-forming collagens (type I and III) as well as cellular
fibronectin, hyaluranic acid and other matrix proteoglycans
and glycoconjugates. There is a loss of endothelial cell
fenestrations and hepatocyte microvilli, and capillarization
of sinusoids, which impedes the metabolic exchange
between blood and liver cells.
The hepatic stellate cells (lies in the space of Disse) is
the principle cell involved in fibrogenesis. In the resting
state these cells have intracellular droplets containing vitamin
A. Stellate cells are activated by factors released when
Indian Medical Gazette — FEBRUARY 2013
adjacent cells are injured. Such factors include Transforming
Growth Factor β1 (TGF-β1) from endothelial, Kupffer cells
and platelets, lipid peroxides from hepatocytes, Platelet
Derived Growth Factors (PDGF) and Epidermal Growth
Factor (EGF) from platelets12. Stellate cell activation is
accompanied by loss of retinoid droplets, cellular
proliferation and enlargement, and increased endoplasmic
reticulum. The cells become contractile. They release
cytokines, chemotactic factors, extracellular matrix and
enzymes that degrade matrix13. The increase in interstitial
matrix is a further stimulus to stellate cell activation.
Imbalance between matrix synthesis and degradation
plays a major role in hepatic fibrogenesis14. The degree of
hepatic fibrosis following hepatocellular injury varies
according to the cause and the balance between the response
of stellate and Kupffer cells to the cytokines and growth
factors that resolves with removal of the insult to severe
scarring and nodule formation (cirrhosis) that is
irreversible15.
Present study (Table 1 and Fig. 1) shows significant
fall in serum Zinc concentrations in liver cirrhosis patients
(p<0.001).
Many of the clinical features of liver cirrhosis have been
linked to zinc deficiency, including loss of body hair,
testicular atrophy, poor apetite, immune dysfunction, altered
taste and smell, reduced Vitamin A and thyroid hormone
metabolism, altered protein metabolism, delayed wound
healing and reduced drug elimination capacity. One of the
most interesting and novel aspects is the role of zinc
deficiency in producing liver cirrhosis is the possible
relationship of zinc and hepatic encephalopathy (Mental and
cerebellar disturbances)16. Zinc is responsible for the
activation of at least 200 metalloenzymes.
There is a hypothesis that zinc ions present in the
cytoplasm at 10 -11 mol/litre and in equilibrium with
numerous zinc metalloenzymes and transcription factors
can act as a master hormone particularly in relation to cell
division and growth7.
Present study (Table 2 and Fig. 2) also shows significant
fall of serum albumin(p<0.001) in liver cirrhosis patients.
As the absorbed zinc is transported to the liver by portal
circulation where active incorporation into metalloenzymes
and plasma proteins such as albumin and α2 macroglobulin
occurs.
Indian Medical Gazette — FEBRUARY 2013
About 80% of plasma zinc is associated with albumin
and rest is tightly bound to high molecular weight protein
α2 macroglobulin. The zinc on albumin is in eqillibrium
with plasma amino acids. Zinc is loosely bound with albumin
and tightly bound to α2 macroglobulin. Albumin level is
lowered in liver cirrhosis, zinc is mostly bound to α2
macroglobulin and became unavailable7.
In this study, fall in serum albumin concentrations with
simultaneous decrease in serum zinc concentrations were
observed, and it can be proposed that low albumin level
may be a cause of zinc deficiency in liver cirrhosis patients.
Evaluation of zinc and albumin status may indicate the
pathophysiological as well as therapeutic role of zinc and
albumin in liver cirrhosis, so that long term supplementation
of zinc and balanced protein diet to achieve nitrogen balance,
may improve the neurological symptoms of cirrhosis of
liver.
Summary
Cirrhosis of liver reflects irreversible chronic injury of
the hepatic parenchyma and include extensive fibrosis in
association with the formation of regenerative nodules. Since
many of the clinical features of cirrhosis of liver simulates
zinc deficiency, and major transporter of zinc in blood is
albumin, (S) zinc and albumin levels were estimated in liver
cirrhosis patients (n=73), in comparison to controls in our
study.
Significant decrease of (S) zinc and albumin levels were
found in liver cirrhosis patients.
From our study it can be hypothesized that some of
the clinical features of liver cirrhosis may be contributed
by zinc deficiency. Our study also indicates that zinc
deficiency may be contributed by reduced (S) albumin
level in liver cirrhosis patients.
According to our study, measured zinc and protein
supplementation in diet may improve some events of liver
cirrhosis like testicular atrophy, immune dysfunction,
reduced vitamin A and thyroid hormone levels, altered
protein metabolism, delayed wound healing and hepatic
encephalopathy.
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