Elsevier

Clinics in Liver Disease

Volume 11, Issue 1, February 2007, Pages 105-117
Clinics in Liver Disease

Metabolic Syndrome and NASH

https://doi.org/10.1016/j.cld.2007.02.013Get rights and content

Clinical and epidemiologic studies have associated non-alcoholic fatty liver with the metabolic syndrome, with insulin resistance as the pivotal pathogenic factor. Obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension contribute to risk for liver disease and to disease progression. The presence of multiple metabolic abnormalities is associated with the severity of liver disease. Patients have a high risk for cardiovascular morbidity and mortality, mediated by early atherosclerosis. This evidence has precise therapeutic implications: only a behavioral approach to lifestyle correction will address all alterations characterizing the metabolic syndrome, including metabolic liver disease.

Section snippets

Non-alcoholic fatty liver disease/non-alcoholic stereohepatitis and the metabolic syndrome

The abstract of the pioneering study of Ludwig and colleagues [1], first describing non-alcoholic fatty liver disease (NAFLD) in 1980, reads, “Most patients were moderately obese, and many had obesity-associated diseases, such as diabetes mellitus.… ” Only a few years later, Reaven [2] described syndrome X as the association of hyperinsulinemia, hyperglycemia, hyperlipidemia, and hypertension, conditions observed frequently in NAFLD and having insulin resistance as their common pathogenic

Current concepts on metabolic syndrome

When Alberti and Zimmet [5], on behalf of a World Health Organization (WHO) committee of experts, proposed the name, metabolic syndrome, for a condition characterized by multiple metabolic abnormalities, they covered a long-debated area. Unfortunately, their provisional classification did not settle the debate, and in the following years there was a surfeit of articles dealing with the pros and cons of this definition. Several international associations and societies have taken sides and

Non-alcoholic fatty liver disease/non-alchoholic steatohepatitis, insulin resistance, and the metabolic syndrome

Insulin resistance is regarded as a hallmark and a causal factor of NAFLD, even in the absence of obesity and diabetes mellitus. Increasingly it is recognized that multiple genetic and acquired factors can influence insulin action and postprandial lipid metabolism. Diet and nutrition, in particular the amount and type of carbohydrate and fat intake, are linked to insulin resistance, increased risk for developing type 2 diabetes mellitus, and impaired postprandial lipid metabolism [22], thus

Obesity

As discussed previously, obesity is associated strongly with NAFLD. The prevalence of NAFLD is as high as 75% in obese persons who are obese, where truncal obesity becomes a risk factor even in patients who have normal BMI. Hepatic steatosis is documented in individuals who are only 10% above ideal body weight, but a few individuals who are morbidly obese do not have NAFLD. This suggests that obesity and NAFLD are consequences of a common underlying disorder (eg, insulin resistance) or that

Implications for treatment

Given the pathophysiologic association of NASH with insulin resistance and the MS, treatment strategies for metabolic liver disease should aim to improve insulin sensitivity and modify the metabolic risk factors or protect the liver from oxidative stress and further insults. Changes in lifestyle remain the baseline approach, and structured weight-reducing programs, based on diet and physical activity, are recommended by international agencies for all components of MS (Fig. 2). NAFLD of any

Summary

The prevalence of MS is expected to increase systematically in the next decades, because of the rising prevalence of obesity and type 2 diabetes mellitus. The prevalence of NAFLD also is expected to increase, and the presence of multiple metabolic disorders is associated with rates of fibrosis progression, NASH, and, finally, cryptogenic cirrhosis or HCC [69].

In the high number of cases potentially progressing to terminal liver failure, the cardiovascular risk associated with insulin resistance

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