Conventional biochemical and serological tests are of little value in
the diagnosis of the liver cirrhosis and the degree of fibrosis and the
activity of fibrogenesis and the presence of hepatocellular carcinoma so
percutaneous liver biopsy is used to assess the extent of liver fibrosis and
fibrogenesis and the presence of hepato-celluar carcinoma but a liver
biopsy is sometimes of questionable value because of the heterogenous
distribution of pathological changes in the liver, so non invasive
biochemical markers for assessing liver cirrhosis in chronic hepatitis and
for detecting malignancy in hepato-cellular carcinoma are being actively
sought to help evaluating the histologic damage and monitor the
progression of fibrosis
Matrix metalloproteinases are key enzymes in the regulation of the
cell matrix composition and in the metabolism of collagen and in the
physiopathology of fibrosis by their ability to cleave and degrade one or
several ECM constituents as well as non-matrix proteins and their activity
is regulated by interaction with a group of TIMPs (tissue inhibitor of
metallo-proteinases).
Gelatinases (type IV collagenases) may be especially important for
the development of organ fibrosis because they degrade type IV
(basement membrane) collagen and thus are involved in the early steps of
tissue remodeling that characterizes chronic viral liver diseases, also may
be especially important in invasion and metastasis of malignant tumors
because they destroy the surrounding extra-cellular matrix (Arthur,2000)
Summary
١١٥
There are two types of gelatinases which are MMP-2 and MMP-9
and studies have shown that serum levels of MMP-2 are increased in
chronic liver disease so the aim of this study is to assess the clinical
significance of MMP-2 as a diagnostic marker in both chronic hepatitis-C
and hepatocellular carcinoma and if there’s any difference between both
conditions and to evaluate if there’s any correlation between MMP-2 and
liver functions (namely, Bilirubin, Albumin and Prothrombin time) and
also with the severity of liver disease, this study was conducted on 50
patients, they were 32 males and 18 females their ages ranged between 30
years and 80 years and all cases were selected from the Internal Medicine
Department of Benha University Hospital in addition to 25 healthy
individuals of matched age and sex served as a control group.
The studied cases included the following groups:
Group I: Included 25 hepatic patients with positive HCV comprised 14
males and 11 females with their mean age (53.12 ± 10.5 years) ± SD.
Group II: Included 25 hepatic patients with positive HCV and with
hepatocellular carcinoma comprised 18 males and 7 females with their
mean age (55.64 ± 10.5 years) ± SD.
Group III (control group): Included 25 apparently healthy individuals
comprised 8 males and 17 females with their mean age (50.04 ± 10.5
years) ± SD.
All patients and controls were subjected to:
1- Full history taking of present illness.
2- Thorough clinical examination.
3- Abdominal ultrasonography to study the size and pattern of liver
and spleen and presence or absence of ascites.
4- Routine laboratory investigations:
Summary
١١٦
a) Complete blood picture.
b) Urine and stool analysis.
c) Serum creatinine.
d) Liver function tests: (Total protein, Serum Albumin,
Bilirubin (Total and Direct), ALT, AST, Alkaline
phosphatase and prothrombin time).
e) Serological test:
Hepatitis-C virus marker determined by Enzyme Linked
immunosorbant Assay (ELISA) and Polymerase Chain Reaction (PCR).
f) Specific laboratory investigations included:
· Alpha fetoprotein (a FP).
· Matrix metalloproteinase-2 (MMP-2).
The present study revealed that:
1- Serum levels of MMP-2 were highly significantly elevated in
patients with chronic hepatitis-C (group I) and in patients with HCC
(group II) than the controls with no significant statistical difference
between both patient groups.
2- Serum levels of MMP-2 correlated significantly with the severity of
liver disease as it showed a significant elevation in child C class
than child B class than child A class.
3- Serum MMP-2 is considered to be derived from the cirrhotic liver
in patients with chronic viral liver disease and correlated with the
degree and staging of fibrosis, so the measurement of serum MMP-
2 is the best test for diagnosing liver cirrhosis in patients with
chronic viral liver disease.
4- Serum MMP-2 levels had a strong correlation with serum markers
of liver function (positive for Bilirubin, AST, ALT, ALP and PT and negative for albumin) in both patient groups (group I and group
II).
5- The MMP-2 levels in an individual patient cannot be used as a
marker for liver function because of a wide overlap in levels
between the different child-Pugh classes but could be used as a
substitute for liver biopsy to assess the extent of liver fibrosis and
fibrogenesis especially when liver biopsy is contraindicated.
6- High serum levels of MMP-2 in patients with HCC may result form
the non tumorous part of the liver rather than from the carcinoma
and no relation between MMP2 and tumor size or tumor
differentiation so it cannot be used as a diagnostic marker for HCC
in the context of chronic liver diseases. |
