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Serum apolipoprotein C-III is independently associated with chronic hepatitis C infection and advanced fibrosis

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Abstract

Background

The hepatitis C virus (HCV) is known to disrupt lipid metabolism, making serum lipoprotein levels good candidates to explore as markers of HCV disease progression. Assessment of the major apolipoproteins (Apo) and their relationship to hepatic fibrosis remain largely unexplored.

Methods

We compared the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and Apo A-I, -B, -C-III, and -E between patients with cleared versus active infection (n = 83), and between those chronically infected patients (n = 216) with advanced versus mild–moderate hepatic fibrosis (METAVIR stage F3–4 vs. F0–2) using multiple logistic regression.

Results

Apo C-III levels were 25% higher in subjects with cleared infection versus those with active infection (p = 0.009). Low levels of Apo C-III (p = 1.3 × 10−5), Apo A-I (p = 2.9 × 10−5), total cholesterol (p = 5.0 × 10−4), LDL-C (p = 0.005), and HDL-C (p = 2.0 × 10−4) were associated with advanced fibrosis in univariate analyses. Multivariable analysis revealed Apo C-III as the most significant factor associated with advanced fibrosis (p = 0.0004), followed by age (p = 0.013) and Apo A-I (p = 0.022). Inclusion of both Apo C-III and Apo A-I in a model to predict advanced fibrosis improved the area under the receiver operator curve only modestly.

Conclusions

Relative to other lipoproteins, low serum Apo C-III levels are the most strongly associated with chronic versus cleared infection and decline with increasing severity of hepatic fibrosis. Apo C-III deserves further attention as a possible marker of HCV disease progression.

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Acknowledgements

The authors would like to thank all of the study participants who contributed their biospecimens and data to the Duke Hepatology Clinic Database and Biorepository, and acknowledge Diane Uzarski, Crystal Cates, Chris Delionbach, and Melissa Austin for continued maintenance of this valuable resource. This study was funded in large part by a generous grant from the David H Murdock Institute for Business and Culture via the M.U.R.D.O.C.K. Study and NIH CTSA award 1 UL1 RR024128-01. Dr. Rowell is supported by NIH Training Grant T32-DK007012-31 at Duke University Medical Center. Dr. Thompson received funding support from the Duke Clinical Research Institute, a generous research gift from the Richard B. Boebel Family Fund, the National Health and Medical Research Council of Australia, and the Gastroenterology Society of Australia. There are no conflicts to disclose.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Metabolism and Nutrition, Duke University, Durham, NC, USA

    J. Rowell & J. R. Guyton

  2. Department of GI/Hepatology Research Program, Duke Clinical Research Institute, Duke University, PO Box 17969, Durham, NC, 27715, USA

    A. J. Thompson, J. G. McHutchison & K. Patel

  3. Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA

    X. Q. Lao & J. J. McCarthy

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  1. J. Rowell
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Correspondence to K. Patel.

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Rowell, J., Thompson, A.J., Guyton, J.R. et al. Serum apolipoprotein C-III is independently associated with chronic hepatitis C infection and advanced fibrosis. Hepatol Int 6, 475–481 (2012). https://doi.org/10.1007/s12072-011-9291-x

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  • DOI: https://doi.org/10.1007/s12072-011-9291-x

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