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Metabolic syndrome cardiovascular disease risk and more
  .....fatty liver has become an issue of major concern due to occurrence of this lesion in subjects with hepatitis C virus (HCV) chronic hepatitis.....The prevalence of fatty liver in the context of HCV (30-70%) is higher than that observed in other forms of liver disease.....
Alimentary Pharmacology & Therapeutics
November 2005
N. Carulli
Dipartimento di Medicine e Specialita Mediche
Universita di Modena e Reggio Emilia
Modena, Italy
Monsieur died of apoplexy two years later. The new job had kept him in idleness and without any exercise, he had grown excessively stout and died of an excess of health (Guy de Maupassant, La Maison Tellier, 1881).
The definition of metabolic syndrome as a cluster of metabolic abnormalities (disturbance in glucose metabolism, obesity, mainly abdominal, hypertension and atherogenic dyslipidemia) sharing insulin resistance as a possible pathogenetic factor is of great clinical relevance for drawing attention to the concurrence of several risk factors for cardiovascular disease (CVD). Indeed due to life style habits of increased caloric intake and reduced or absent physical activity, the prevalence of the metabolic syndrome will continue to rise as well as obesity, diabetes type 2 and CVD.
The same genesis of insulin resistance, the mechanistic relation linking insulin resistance to the various metabolic abnormalities of the syndrome, the different phenotypes of the syndrome, the role of the adipose tissue as an endocrine organ and the relevance of genetic factors are all important issues under active investigation.
Several definitions of the metabolic syndrome proposed by health organizations and scientific societies have emphasized one or the other of the different components of the syndrome, however there is much overlap among the criteria utilized for diagnosis. A recent report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program has proposed a simple working diagnosis of the syndrome using criteria based on the values of variables such as: fasting blood glucose, triglycerides, HDL cholesterol, blood pressure and waist circumference.1
Although this proposed definition might have a low sensitivity in detecting subjects with insulin resistance,2 it has the potential to be used in epidemic studies and to easily identify and manage individuals with the syndrome.
To the well-known components of the clinical spectrum of the metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has recently been added. This increasingly recognized condition, including a wide spectrum of lesions from simple steatosis to end stage liver disease, has relation to insulin resistance.3, 4 It is possible that NAFLD is responsible for those forms of cirrhosis termed as 'cryptogenic' due to the absence of known etiology5, 6 and may adversely affect liver transplant outcome.
The knowledge this 'added' risk of the metabolic syndrome bears on clinical practice is that it provides the pathophysiological basis of so far unexplained and overlooked hypertransaminasemia often observed in subjects with diabetes and obesity.7, 8 We are now aware that the natural history of such borderline increase of serum transaminases might not be so benign as it was supposed to be.9
Furthermore, fatty liver has become an issue of major concern due to occurrence of this lesion in subjects with hepatitis C virus (HCV) chronic hepatitis. Both NAFLD and HCV hepatitis are the most common liver disease potentially bearing significant morbidity. The prevalence of fatty liver in the context of HCV (30-70%) is higher than that observed in other forms of liver disease. This suggest a mechanistic causal relationship between HCV and host factors.10
On one hand, HCV genotype 3 seems to be cytopathic in that the extent of steatosis relates to the viral load and the clearance of the virus following anti-viral therapy leads to resolution of the steatosis; on the other hand, the mechanism(s) responsible of NAFLD, linked to insulin resistance, seems to apply also for the steatosis in genotype non-3 HCV hepatitis.
In this context, evidence suggests that steatosis seems to exert an aggravating role in the progression of the disease towards fibrosis and HCC and to have a negative impact on the response to anti-viral treatment. Important implication of this observation is that treatment aimed to correct steatosis, adjunctive to the anti-viral therapy, could improve in these subjects the outcome of HCV hepatitis.11
A better understanding of the complex mechanism behind the metabolic syndrome will perhaps lead to better therapeutic strategies for its prevention and control. Actually several drug therapies for the treatment of CVD risks factors are available. Furthermore, drugs able to reduce insulin resistance, such as metformin and tiazolidinediones, already in the therapeutic armamentarium of type 2 diabetes, could be used in subjects with the metabolic syndrome as a preventive measure.12
To date, however, a first level management of the syndrome should consider life style changes such as increased physical activity, optimal weight maintenance and diet composition.
The reviews in this supplement to Alimentary Pharmacology and Therapeutics provide an authoritative summary of the current knowledge on some important aspects of the metabolic syndrome.
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