The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It encompasses a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Growing evidence links NAFLD to cardiovascular (CV) disease; however, the association between the histologic severity of NAFLD and CV risk remains poorly understood.


OBJECTIVE
To assess the relationship between severity of liver injury and CV risk markers in a large, well-characterized group of patients with biopsy-proven NAFLD.


METHODS
Our cohort consisted of 83 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were subsequently divided into three groups: normal biopsy (n=11) simple steatosis (n=36), and NASH (n=36). CV risk markers included: triglyceride/high-density lipoprotein (HDL), total cholesterol/HDL, and low-density lipoprotein/HDL ratios.


RESULTS
All lipid ratios were found to be significantly associated with NAFLD (p<0.05) after adjusting for age and gender. More importantly, there was a stepwise, statistically significant increase in lipid ratios from patients with normal biopsies to patients with simple steatosis to those with NASH (p<0.05). A positive correlation was found between the lipid ratios and NAFLD activity score (NAS) as well as the individual histological features of the NAS (steatosis, inflammation, and ballooning) with the strongest correlation being with NAS (rho (95% CI) 0.41 (0.21, 0.62), p<0.001).


CONCLUSIONS
In patients with NAFLD, the histologic severity of liver injury and inflammation is strongly associated with an increased CV risk and an atherogenic lipid profile.
Alkhouri
Naim
N
Department of Pediatric Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. alkhoun@ccf.org.
Tamimi
Tarek Abu-Rajab
TA
Yerian
Lisa
L
Lopez
Rocio
R
Zein
Nizar N
NN
Feldstein
Ariel E
AE
D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000473:pathology*; D005260:Female; D006505:Hepatitis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009820:Ohio; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol