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The Inflamed Liver and Atherosclerosis: A Link Between Histologic Severity of Nonalcoholic Fatty Liver Disease and Increased Cardiovascular Risk

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Abstract

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.

Aim

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).

Conclusion

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.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

MS:

Metabolic syndrome

BMI:

Body mass index

IR:

Insulin resistance

CV:

Cardiovascular

TG:

Triglyceride

TC:

Total cholesterol

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

HOMA:

Homeostatic model assessment

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

BP:

Blood pressure

NAS:

NAFLD activity score

WC:

Waist circumference

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Acknowledgments

This work was supported by NIH DK076852 to AEF.

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Authors and Affiliations

  1. Department of Pediatric Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Naim Alkhouri & Ariel E. Feldstein

  2. Digestive Disease Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Tarek Abu-Rajab Tamimi, Lisa Yerian & Nizar N. Zein

  3. Quantitative Health Sciences, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Rocio Lopez

  4. Cell Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Ariel E. Feldstein

Authors
  1. Naim Alkhouri
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  2. Tarek Abu-Rajab Tamimi
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  3. Lisa Yerian
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  4. Rocio Lopez
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  5. Nizar N. Zein
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  6. Ariel E. Feldstein
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Correspondence to Naim Alkhouri.

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Alkhouri, N., Tamimi, T.AR., Yerian, L. et al. The Inflamed Liver and Atherosclerosis: A Link Between Histologic Severity of Nonalcoholic Fatty Liver Disease and Increased Cardiovascular Risk. Dig Dis Sci 55, 2644–2650 (2010). https://doi.org/10.1007/s10620-009-1075-y

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  • DOI: https://doi.org/10.1007/s10620-009-1075-y

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