Prevalence of NAFLD and cardiovascular risk assessment in patients with newly diagnosed of familial combined hyperlipidemia

Background: Nonalcoholic fatty liver disease (NAFLD), generally linked to obesity and metabolic syndrome, is the most common cause of liver disease worldwide. Patients with NAFLD compared to those without have higher risk of both cardiovascular and neoplastic disease and therefore have worse life expectation. NAFLD, defined as liver steatosis not caused by other known causes of liver disease, is characterized by a wide spectrum of clinic manifestation ranging from simple steatosis to nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma. NAFLD patients are often affected by other metabolic disorders such as diabetes mellitus and/or dyslipidemia. Dyslipidemias are disorders of lipid metabolism due to lipid accumulation in blood vessel, phenotypically classifiable into hypercholesterolemia, hypertriglyceridemia, and mixed forms. The most important complications of dyslipidemias are atherosclerosis and cardiovascular (CV) disease. No sufficient data are available on the prevalence and clinical significance of NAFLD in patients with new diagnosis of dyslipidemia. Aim: Aim of the study was to evaluate the prevalence of NAFLD and to assess CV risk in patients with new diagnosis of familial combined hyperlipemia. Materials and methods: We enrolled 80 patients [mean age 52.5 ±9.45 SD; median 53.5 (range 18-75 years); 37 males/43 females] referred by general practitioners to the Department of Internal Medicine of Messina University Hospital. All patients had dyslipidemia that was defined as follows: total cholesterol higher than 240 mg/dl and/or LDL higher than 160 mg/dl, HDL lower than 40 mg/dl (man) or 50 mg/dl (women), and ApoB >120 mg/dl. Steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB4). Presence of atherosclerosis was assessed by carotid ultrasound to identify carotid intima media thickness (c-IMT) and presence/absence of plaque. Results: Liver steatosis was found in 56/80 patients (70%) by US examination. According to HSI, liver steatosis was diagnosed in 34 patients (42.5%), absent in 8 patients (10%), inconclusive in 38 patients (47.5%). US examination identified liver steatosis in 22 patients in whom HSI did not reveal steatosis, whereas 4 patients had HSI diagnostic for steatosis, but they had no US steatosis. We therefore analyzed two group of patients: a) the steatosis group (subjects with steatosis diagnosed by either US or HSI [n=60, 75%]) and b) a group without steatosis, where both US and HSI excluded steatosis (n= 20, 25%). We found that patients with steatosis had a significantly higher BMI compared to those without (p < 0.05). Liver steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely correlated with HDL-cholesterol (p < 0.05). Liver fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and c-IMT (p< 0.05), and fibrosis assessed by FIB4 was significantly associated with sex (p < 0.05), c-IMT (p < 0.05) and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque (OR 4.760, p < 0.05), independently from arterial hypertension, sex and smoke habit (OR 4.624, p=0.008 from the multivariable model). Conclusion: In our cohort of patients with newly diagnosed familial combined hyperlipemia we found a high prevalence of hepatic steatosis. Indeed, the risk of atherosclerotic plaque increased in patients with liver fibrosis, making possible to speculate a possible connection between liver disease and CV damage in dyslipidemic patients.