Abstract

BackgroundDyslipidemia, typically recognized as high serum triglyceride, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease (NAFLD). However, low LDL-C levels could result from defects in lipoprotein metabolism or impaired liver synthetic function, and may serve as ab initio markers for unrecognized liver diseases. Whether such relationships exist in the general population has not been investigated. We hypothesized that despite common conception that low LDL-C is desirable, it might be associated with elevated liver enzymes due to metabolic liver diseases.Methods and FindingsWe examined the associations between alanine aminotransferase (ALT), aspartate aminotransferase (AST) and major components of serum lipid profiles in a nationally representative sample of 23,073 individuals, who had no chronic viral hepatitis and were not taking lipid-lowering medications, from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with triglyceride. After adjusting for potential confounders, individuals with LDL-C less than 40 and 41–70 mg/dL were associated with 4.2 (95% CI 1.5–11.7, p = 0.007) and 1.6 (95% CI 1.1–2.5, p = 0.03) times higher odds of abnormal liver enzymes respectively, when compared with those with LDL-C values 71–100 mg/dL (reference group). Surprisingly, those with HDL-C levels above 100 mg/dL was associated with 3.2 (95% CI 2.1–5.0, p<0.001) times higher odds of abnormal liver enzymes, compared with HDL-C values of 61–80 mg/dL.ConclusionsBoth low LDL-C and high HDL-C, often viewed as desirable, were associated with significantly higher odds of elevated transaminases in the general U.S. adult population. Our findings underscore an underestimated biological link between lipoprotein metabolism and liver diseases, and raise a potential need for liver evaluation among over 10 million people with particularly low LDL-C or high HDL-C in the United States.

Highlights

  • Measurement of triglyceride and cholesterol concentrations among different lipoproteins as part of the serum lipid panel is a routine part of cardiovascular disease risk stratification

  • Dyslipidemia typically refers to elevated low-density lipoprotein cholesterol (LDL-C) or triglyceride or low high-density lipoprotein cholesterol (HDL-C), a pattern that is associated with cardiovascular risk and is frequently seen in nonalcoholic fatty liver disease (NAFLD) [3,4]

  • NAFLD, a spectrum of disease ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis, is the most common form of chronic liver disease and the most likely cause of elevated transaminases in otherwise healthy individuals [4,5]

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Summary

Introduction

Measurement of triglyceride and cholesterol concentrations among different lipoproteins as part of the serum lipid panel is a routine part of cardiovascular disease risk stratification. Dyslipidemia typically refers to elevated LDL-C or triglyceride or low HDL-C, a pattern that is associated with cardiovascular risk and is frequently seen in nonalcoholic fatty liver disease (NAFLD) [3,4]. Low LDL-C levels could result from defects in lipoprotein metabolism or impaired liver synthetic function, and may serve as ab initio markers for unrecognized liver diseases. Whether such relationships exist in the general population has not been investigated. We hypothesized that despite common conception that low LDL-C is desirable, it might be associated with elevated liver enzymes due to metabolic liver diseases

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