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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2015  |  Volume : 12  |  Issue : 1  |  Page : 24-28

Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome


Department of Clinical Pathology, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Web Publication14-Jul-2015

Correspondence Address:
Dr. Udenze Ifeoma Christiana
Department of Clinical Pathology, College of Medicine, University of Lagos, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1595-9587.160764

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  Abstract 

Aims and objectives: The aim of this study is to determine the plasma levels of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH) in people with metabolic syndrome and to determine the association between the liver enzymes and obesity, insulin resistance, interleukin 6 (IL-6), and C-reactive protein (CRP) in adult Nigerians with metabolic syndrome. Materials and Methods: This was a case control study of 50 adult men and women with metabolic syndrome, and 50 age- and sex-matched males and females without metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII) criteria. Written informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an overnight fast. The ethics committee of the Lagos University Teaching Hospital in Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the student's t-test. Regression and correlation analysis were used to determine the associations between variables. Statistical significance was set at P < 0.05. Results: There was a statistically significant increase in the liver enzymes ALP (P = 0.031), ALT (P = 0.019), and GGT (P = 0.037), as well as in the inflammatory markers CRP (P = 0.019) and the cytokine IL-6 (P = 0.040) between the two study groups. ALP and ALT showed significant correlation with waist circumference, BMI, fasting insulin, and waist/hip ratio (P < 0.05). Multivariate regression also identified ALT, AST, and ALP to be associated with IL-6 and CRP (P < 0.05). Conclusion: Liver enzyme levels were increased in metabolic syndrome and associated with obesity, fasting insulin, and CRP. Elevated liver enzymes may indicate dysmetabolism and increased cardiovascular risk in Nigerian adults with metabolic syndrome.

Keywords: CRP, inflammation, liver enzymes, metabolic syndrome


How to cite this article:
Christiana UI, Obiefuna AI, Egbuagha EU, Oshodi TA. Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome. J Clin Sci 2015;12:24-8

How to cite this URL:
Christiana UI, Obiefuna AI, Egbuagha EU, Oshodi TA. Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome. J Clin Sci [serial online] 2015 [cited 2018 Nov 19];12:24-8. Available from: http://www.jcsjournal.org/text.asp?2015/12/1/24/160764


  Introduction Top


Metabolic syndrome is a constellation of several cardiometabolic risk factors such as abdominal obesity, insulin resistance, hypertension, and dyslipidemia. [1] Individuals with the syndrome are at increased risk for atherosclerotic cardiovascular disease. [2]

Low-grade chronic inflammation has been associated with metabolic syndrome and has also been linked with the development of atherosclerosis and cardiovascular disease in people with metabolic syndrome. [3] Abdominal/central obesity appears to be a major contributor to the low-grade inflammation associated with metabolic syndrome. [4],[5]

The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing in both the developed and developing countries, and this increased prevalence is linked with the obesity and metabolic syndrome pandemic. [6],[7],[8]

There have been strong associations between components of metabolic syndrome and both NAFLD and NASH. [6],[9],[10] NAFLD and NASH can progress to end-stage liver disease and increase the risk of mortality. [11],[12] NAFLD is considered to be the liver manifestation of metabolic syndrome. [3]

The progression of NAFLD and NASH involves an initial metabolic disturbance with an abnormal deposition of fat within the liver parenchyma, which may be followed by increased oxidative stress and cytokine production. [13],[14]

It has been hypothesized that inflammatory processes that occur in the liver contribute to the systemic inflammation that characterizes metabolic syndrome. [15]

Studies have associated elevated liver enzymes with metabolic syndrome [3],[16] and increased levels of the liver enzymes have predicted the development of impaired glucose tolerance and incident type 2 diabetes in individuals with metabolic syndrome. [17] Few studies, however, have evaluated liver function tests and metabolic abnormalities in relation to the markers of inflammation. This study aims to examine the relationship between liver function tests, inflammation, and components of metabolic syndrome in adult Nigerians.


  Materials and Methods Top


Subjects

We studied 50 adult Nigerian males and females between the ages of 30 and 60 years who were diagnosed with metabolic syndrome and compared them with 50 age- and sex-matched controls without metabolic syndrome. Subjects with known inflammatory disease and coronary disease were excluded from the study. The subjects with metabolic syndrome were drawn from among patients attending the Obesity and Metabolic Clinic of the Lagos University Teaching Hospital and the controls were members of staff of the hospital. Informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. The Ethical Research and Review Committee of the hospital approved the study protocol.

Definitions

The definition of metabolic syndrome was based on the NCEP-ATPIII criteria [1] requiring a combination of at least three of the following five criteria: Abdominal circumference ≥102 cm in males or ≥88 cm in females, HDL cholesterol < 1.03 mmol/L (<40 mg/dL) in males or <1.3 mmol/L (<50 mg/dL) in females, triglycerides ≥ 1.7 mmol/L (≥150 mg/dL), blood pressure ≥ 130/85 mmHg, or the patient receiving hypotensive treatment and fasting glycemia > 6.1 mmol/L (>110 mg/dL).

Elevated liver enzymes were defined as greater than the fourth quartile of the study population.

Methods

Venous blood samples were collected from each subject after a 12-h fast and used for assays of glucose, total and HDL cholesterol, triglycerides, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) using reagents from Randox Laboratories Limited, (Antrim, UK, BT 29 4QY), on a semiautomatic biochemistry analyzer (BS3000P) (Sinnowa Medical Science and Technology Company Limited, Nanjing, China, 211135). Serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), and insulin were determined using reagents from Biovendor Laboratories (62100, Brno, Czech Republic) by an enzyme-linked immunoassay technique on Acurex Plate Read (Acurex Diagnostics, Ohio, USA, 419-872-4775).

Statistical analysis

The data were analyzed using the IBM SPSS version 19.0 package. An independent student's t-test was used to test the differences in the mean values for the continuous variables. Regression and correlation analysis were used to determine the association between variables. Statistical significance was set at P < 0.05.


  Results Top


The study population included 20 men and 30 women with metabolic syndrome with a mean age of 47.84 ± 6.4 years and age- and sex-matched controls. ALT, ALP, GGT, and AST elevation occurred in 7.1%, 10.7%, 54.54%, and 42.84% respectively, in the group with metabolic syndrome. The sociodemographic characteristics of the study participants are shown on [Table 1]. The ethnic distribution of the study participants, the type of work they were engaged in, their level of education, as well as their marital status were comparable between the subjects with metabolic syndrome and the control subjects without metabolic syndrome.
Table 1: Socio-demographic characteristics of study participants


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With regards to their smoking habits, 90% of the group with metabolic syndrome were nonsmokers compared to 98% of the control group without metabolic syndrome who also did not smoke. The difference between the two groups was not statistically significant. Twenty-two percent of those with metabolic syndrome drank alcohol, 68% did not drink, and 10% drank alcohol occasionally, compared to 8% in the control group who drank alcohol, 72% who did not drink, and 20% who drank alcohol occasionally. There was, however, no statistically significant difference in the alcohol habits of the two study groups.

[Table 2] shows the clinical and laboratory characteristics of the study participants.

The age- and sex-matched cases and controls differed in some of metabolic syndrome parameters. The inflammatory markers IL-6 and CRP were significantly higher in the group with metabolic syndrome. The liver enzymes ALP, ALT, and GGT were also significantly higher in the group with metabolic syndrome.
Table 2: Clinical and laboratory characteristics of study participants with and without metabolic syndrome


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[Table 3] shows the correlation coefficients of the associations of some of the components of metabolic syndrome with the liver enzymes ALP and ALT. AST, GGT, and LDH did not show a significant association with any of the components of the syndrome.
Table 3: Correlation of components of metabolic syndrome with ALP and ALT


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ALP showed a significant association with waist circumference, Body Mass Index (BMI), and insulin, while ALT showed a significant association with waist circumference and Waist/Hip ratio (WHR) (P < 0.05).

[Table 4] shows the regression characteristics of IL-6 and CRP with liver enzymes.
Table 4: Regression of IL-6 and CRP with liver enzymes


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For every unit increase in IL-6, the ALT, AST, and ALP increased by a factor of 0.075, 0.127, and 0.15 respectively. For every unit increase in CRP, the ALT, AST, and ALP increased by a factor of 0.34, 0.16, and 2.44 respectively.


  Discussion Top


This study reports significantly higher levels of the liver enzymes ALP, ALT, and GGT in individuals with metabolic syndrome compared to controls [Table 2]. This is similar to reports from several studies from different regions and countries. A cross-sectional study on Taiwanese adults [18] also reported increased levels of the liver enzymes AST, ALT, and GGT in metabolic syndrome. A study by Villegas et al.; [16] in middle-aged urban Chinese men reported elevated levels of AST and ALT in those with metabolic syndrome. Studies where the participants were classified based on the presence of one or more components of metabolic syndrome, also reported elevated liver enzyme levels compared to controls. [16],[17] Studies that reported within reference interval results for the liver enzymes nevertheless noted that metabolic syndrome was associated with the upper quartiles of the reference interval liver enzyme results. [19],[20]

Elevated liver enzymes are markers of fatty liver changes and therefore crude markers of NAFLD. NAFLD describes a clinico-pathologic condition characterized by a significant deposit of fat in the liver parenchyma. It is a spectrum of disorders ranging from a simple steatosis to more severe forms that include NASH, which may progress to fibrosis and hepatic cirrhosis. [21] NAFLD represents the liver component of metabolic syndrome. Definitive diagnosis of NAFLD and NASH is by histology following liver biopsy. Fatty liver can also be visualized by the use of ultrasonography, but this procedure is not cost-effective in resource-poor settings and lacks sufficient sensitivity and specificity on a population level for screening apparently healthy individuals. Therefore, the quantitative analysis of liver enzymes becomes an important diagnostic tool. Prospective population-based studies to determine the cut-off levels for the liver enzymes for the diagnosis of NAFLD and metabolic syndrome will be useful.

This study also reports significant positive association between the enzyme ALP and components of metabolic syndrome: Waist circumference, BMI, and fasting insulin levels. ALT also had a positive association with waist circumference and WHR [Table 3]. Many authors also reported associations of increasing liver enzyme levels with a number of the components of metabolic syndrome. Nannipieri et al.[17] reported an association between ALP and waist circumference and BMI in subjects with metabolic syndrome and type 2 diabetes. Villegas et al. [16] reported an association of ALT and AST with BMI and WHR also in subjects with metabolic syndrome and type 2 diabetes and Sternvil et al.[20] reported an association of ALT with metabolic syndrome and its components. Worthy of note here is the association of the liver enzymes with one or other of the markers of general obesity (BMI) and abdominal obesity (waist circumference and WHR). There are some data linking obesity and elevated liver enzymes. [22],[23] Obesity is a state of increased adiposity, which is associated with insulin resistance and dysmetabolism. [24] In the hepatocytes, free fatty acids are normally oxidized or incorporated into triglyceride or cholesterol esters in the presence of normal insulin levels. In a state of insulin resistance, the adipocytes are resistant to the effects of insulin. There is decreased fatty acid incorporation into tryglycerides in the adipocytes and increased efflux of free fatty acids from adipose tissue under the influence of hormone-sensitive lipase. The increased free fatty acid flux to the liver causes increased hepatic very-low-density lipoprotein (VLDL) production and steatosis. [25]

Alcohol consumption is also associated with increased serum levels of ALT and AST, [26] but in this study, only a small percentage of the cases and controls take alcohol and there was no statistically significant difference in alcohol consumption between the two groups [Table 1].

This study also found increased levels of the markers of inflammation IL-6 and CRP in the group with metabolic syndrome [Table 2] and a significant association of IL-6 and CRP with ALP, ALT, and AST in our study population [Table 4].

The adipose tissue has been identified as the major regulator of chronic low-grade inflammation in patients with metabolic syndrome. [27],[28] Adipose tissue produces proinflammatory cytokines, such as tumor necrosis factor-α and IL-6, which stimulates the liver to produce the acute phase reactant, CRP. [29]

CRP has been shown to be a strong predictor of incident myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. [30],[ 31]

Similar to infiltration of lipoprotein particles into the arterial wall, fat accumulation in the liver stimulates hepatic cytokine production, which could further contribute to the increased CRP levels.

The association between raised liver enzyme levels and increased IL-6 and CRP concentrations suggests that inflammatory processes that accompany NAFLD contribute to the systemic inflammation observed in subjects with metabolic syndrome.

It is important that nonspecific elevations in liver enzymes are not disregarded, especially in a setting of metabolic syndrome, as they correlate with specific histolopathologic features. [32]

Given the association between inflammation, CRP, and cardiovascular events, these liver abnormalities may be relevant not only in relation to dysmetabolism but also in the context of cardiovascular risk.


  Conclusion Top


Metabolic syndrome and its components are associated with elevations in liver enzymes in adult Nigerians. The liver enzyme abnormalities are also positively associated with IL-6 and CRP levels and this may relate to the cardiovascular risk status of people with metabolic syndrome.

Limitations of the study

The study was based on total enzyme assays. Isoenzyme studies were not done to isolate liver fraction.

Source of funding

No financial support exists.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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