Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease

for the NASH Clinical Research Network

Research output: Contribution to journalArticle

Abstract

Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology in order to identify markers of disease activity and severity in patients with biopsy-proven NAFLD. Thirty-two plasma biomarkers chosen a priori as possible discriminators of NAFLD were measured in participants enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network. Dichotomized histologic outcomes were evaluated using centrally read biopsies. Biomarkers with statistically significant associations with NAFLD histology were evaluated in multivariable models adjusted for clinical factors. Of 648 participants (74.4% white, 61.7% female, mean age 47.7 years), 58.0% had definite NASH, 55.5% had mild/no fibrosis (stage 0-1), and 44.4% had significant fibrosis (stage 2-4). Increased activated plasminogen activator inhibitor 1 had a strong association with definite NASH compared to not NASH or borderline NASH in multivariable analysis (odds ratio = 1.20, 95% confidence interval 1.08-1.34, P < 0.001). Biomarkers associated with significant fibrosis (versus mild/no fibrosis) in multivariable analysis included higher levels of interleukin-8, monocyte chemoattractant protein-1, resistin, soluble interleukin-1 receptor I, soluble interleukin-2 receptor alpha, and tumor necrosis factor alpha and lower levels of insulin-like growth factor 2. Conclusions: Specific plasma biomarkers are significantly associated with disease activity and severity of fibrosis in NAFLD and are potentially valuable tools for noninvasive stratification of patients with NAFLD and identification of targets for therapeutic intervention. (Hepatology 2017;65:65-77).

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
JournalHepatology
Volume65
Issue number1
DOIs
StatePublished - Jan 1 2017

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Liver Diseases
Biomarkers
Fibrosis
Histology
Non-alcoholic Fatty Liver Disease
Interleukin-2 Receptor alpha Subunit
Resistin
Biopsy
Interleukin-1 Receptors
Chemokine CCL2
Plasminogen Activator Inhibitor 1
Somatomedins
Gastroenterology
Interleukin-8
Tumor Necrosis Factor-alpha
Odds Ratio
Confidence Intervals
Liver
Therapeutics
Research

ASJC Scopus subject areas

  • Hepatology

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Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. / for the NASH Clinical Research Network.

In: Hepatology, Vol. 65, No. 1, 01.01.2017, p. 65-77.

Research output: Contribution to journalArticle

for the NASH Clinical Research Network. / Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. In: Hepatology. 2017 ; Vol. 65, No. 1. pp. 65-77.
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abstract = "Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology in order to identify markers of disease activity and severity in patients with biopsy-proven NAFLD. Thirty-two plasma biomarkers chosen a priori as possible discriminators of NAFLD were measured in participants enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network. Dichotomized histologic outcomes were evaluated using centrally read biopsies. Biomarkers with statistically significant associations with NAFLD histology were evaluated in multivariable models adjusted for clinical factors. Of 648 participants (74.4{\%} white, 61.7{\%} female, mean age 47.7 years), 58.0{\%} had definite NASH, 55.5{\%} had mild/no fibrosis (stage 0-1), and 44.4{\%} had significant fibrosis (stage 2-4). Increased activated plasminogen activator inhibitor 1 had a strong association with definite NASH compared to not NASH or borderline NASH in multivariable analysis (odds ratio = 1.20, 95{\%} confidence interval 1.08-1.34, P < 0.001). Biomarkers associated with significant fibrosis (versus mild/no fibrosis) in multivariable analysis included higher levels of interleukin-8, monocyte chemoattractant protein-1, resistin, soluble interleukin-1 receptor I, soluble interleukin-2 receptor alpha, and tumor necrosis factor alpha and lower levels of insulin-like growth factor 2. Conclusions: Specific plasma biomarkers are significantly associated with disease activity and severity of fibrosis in NAFLD and are potentially valuable tools for noninvasive stratification of patients with NAFLD and identification of targets for therapeutic intervention. (Hepatology 2017;65:65-77).",
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