Associations between liver histology and carotid intima-media thickness in patients with nonalcoholic fatty liver disease.

Carotid Intima-Media Thickness in Patients With Nonalcoholic Fatty Liver Disease To the Editor: NAFLD is a clinicopathological syndrome that is closely associated with visceral obesity, dyslipidemia, insulin resistance, and type 2 diabetes, thus suggesting that NAFLD is another feature of the metabolic syndrome (MetS).1 Recent cross-sectional studies2–4 have shown that NAFLD is associated with increased carotid intimamedia thickness (IMT) as a reliable marker of early atherosclerosis.5 However, in these studies the NAFLD diagnosis was exclusively based on ultrasound imaging, but was not confirmed by liver biopsy, which is the best diagnostic tool for confirming NAFLD.1 The aim of this study was to assess whether patients with biopsy-proven NAFLD had greater carotid IMT than control subjects and to evaluate whether there were significant associations between liver histopathology and carotid IMT among NAFLD patients. Fifty consecutive patients with NAFLD were recruited from clinics. All patients had chronically elevated liver enzymes. The NAFLD diagnosis was based on liver biopsy and exclusion of known etiologic factors of chronic liver disease. Seven men and 4 women had preexisting type 2 diabetes, 8 managed their diabetes with diet alone, and 3 were taking metformin. The control group, recruited from hospital staff member and relatives, consisted of 40 healthy volunteers with normal liver function tests and normal liver ultrasonography, who were comparable for age, sex, and body mass index (BMI). The protocol was approved by the local Ethical Committee. Plasma liver function tests and other biochemical blood measurements were determined by standard laboratory procedures. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR score).6 The presence of MetS was defined by the Adult Treatment Panel (ATP) III criteria.7 Carotid IMT was ultrasonographically measured by a single trained operator, who was blind to clinical features of participants. Carotid IMT was measured at the level of the common carotid artery far wall, as previously reported.2 Repeated measurements on the same subjects gave coefficients of variation within 8%. A pathologist blinded to subjects’ details scored liver biopsy specimens using the classification of Brunt et al.8 Nonalcoholic steatohepatitis (NASH) was defined as the presence of steatosis plus lobular inflammation plus hepatocellular ballooning or steatosis plus any stage of fibrosis. Liver histopathology results were steatosis alone in 7 subjects, NASH with fibrosis stage of 0 in 14 subjects, NASH/fibrosis stage 1 in 16 subjects, NASH/fibrosis stage 2 in 8 subjects, and NASH/fibrosis stage 3 in 5 subjects; none had cirrhosis (a fibrosis stage of 4). By study design, cases and controls were almost identical in terms of sex (M/F 30/20 versus 26/14), age (mean SD; 46 4 versus 46 3 years), and BMI (26.6 1.6 versus 26.2 1.8 kg/m). NAFLD patients had higher liver enzymes (AST 48 21 versus 22 3 U/L; ALT 102 50 versus 24 4 U/L; P 0.001), but comparable values of LDL cholesterol concentration (3.20 0.3 versus 3.22 0.3 mmol/L) and smoking status (20% versus 22.5%). As shown in the Table, HOMA-IR score and prevalence of MetS were significantly increased in NAFLD patients. They also had a markedly greater carotid IMT than controls, with no differences between sexes (not shown). Additionally, carotid IMT was significantly different between patients with NASH, patients with simple steatosis, and controls. The marked differences in carotid IMT among the groups were little affected by adjustment for age, sex, HOMA-IR score, and MetS. Results did not change after excluding diabetic