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The prevalence of nonalcoholic fatty liver disease (NAFLD) has been estimated to be between 20% and 30% in the general population, but this value is much higher (approximately 70% to 80%) in individuals with type 2 diabetes. Increasing recognition of NAFLD and its strong relationship with metabolic syndrome has stimulated an interest in its possible role in the development of cardiovascular disease (CVD) [Targher G et al. Diabetologia 2008]. Christopher Byrne, MB, PhD, University of Southampton and Southampton University Hospitals Trust Southampton, UK, and colleagues presented findings from a small retrospective study on the relation between NAFLD progression and risk of CVD, especially in patients with diabetes.

The study of 112 patients with biopsy-proven NAFLD used the Kleiner score, a histological measure of NAFLD severity [Kleiner D et al. Hepatology 2005]. Kleiner scores assess the degree of steatosis, lobular inflammation, hepatocyte “ballooning,” and fibrosis, with higher scores indicating more severe liver disease. The primary aim of the study was to see if this histopathological marker correlated with cardiovascular (CV) risk and if scores were higher in people who were already known to have a high CV risk (eg, those with diabetes).

Inclusion criteria included participant age >18 years; biopsy-proven NAFLD with associated Kleiner score; no preexisting underlying liver disorders (eg, alcoholic liver disease, autoimmune hepatitis, primary biliary cirrhosis), and lifetime weekly alcohol consumption that excluded harmful levels of consumption (<35 units [women] and <50 units [men]). The mean age of the study cohort was 48 years, and the mean Kleiner score was 5.3. Thirty-two subjects (31%) had diabetes. The median Framingham Risk Score (FRS) was 13.20% (16.20), and the median QRISK score was 7.85% (16.73). The mean body mass index (BMI) of participants was 34.33±5.91 kg/m².

Kleiner scores showed a high association with both CV risk models—FRS (95% CI, 1.1164 to 3.226; p<0.001; Figure 1) and QRISK2 (95% CI, 1.109 to 2.631; p<0.001; Figure 2). They were also higher in the subgroup with diabetes compared with participants without the disease (6.4±2.0 vs 4.7±2.1, respectively). The Kleiner score was associated with HbA1C (95% CI, 0.080 to 0.725; p=0.015), and diabetes was independently associated with Kleiner score (p=0.04).

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Figure 1.

Kleiner Score is Associated with FRS.

Reproduced with permission from C Byrne, MB, PhD.

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Figure 2.

Kleiner Score is Associated with QRISK2.

Reproduced with permission from C Byrne, MB, PhD.

The authors found a moderately strong association between a gold standard measure of NAFLD disease severity (Kleiner score) and two estimates of 10-year CVD risk scores. The relationships were independent of markers of glucose control (or diabetes) and obesity. Kleiner score was higher in people with diabetes, and diabetes was also independently associated with Kleiner score. Measures of body fat (BMI and truncal fat) were not strongly associated with Kleiner scores.

These findings are consistent with and provide further insight into understanding data from several epidemiological studies that have shown that NAFLD, especially in its more severe forms, is linked to an increased risk of CVD, independent of underlying cardiometabolic risk factors. The data from Prof. Byrne and colleagues suggest that NAFLD is not merely a marker of CVD but may also be actively involved in its pathogenesis, via a worsening of CV risk factors that occurs in more severe forms of NAFLD. “We need more prospective studies to see what markers may be used to help stratify who requires a diagnostic liver biopsy to diagnose the severity of NAFLD and how best to manage people who have NAFLD,” said Prof. Byrne.

• © 2011 MD Conference Express®