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Elevated plasma copeptin levels identify the presence and severity of non-alcoholic fatty liver disease in obesity

Barchetta, Ilaria LU ; Enhörning, Sofia LU ; Cimini, Flavia Agata; Capoccia, Danila; Chiappetta, Caterina; Di Cristofano, Claudio; Silecchia, Gianfranco; Leonetti, Frida; Melander, Olle LU and Cavallo, Maria Gisella (2019) In BMC Medicine 17(1).
Abstract

Introduction: Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the... (More)

Introduction: Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH. Methods: For this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific). Results: Obese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD- 6.4 ± 2.6; and non-ob/NAFLD- 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02-2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components. Conclusions: Increased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention.

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type
Contribution to journal
publication status
published
subject
keywords
Antidiuretic hormone, Copeptin, Fatty liver, Metabolic syndrome, NAFLD, NASH, Obesity, Vasopressin
in
BMC Medicine
volume
17
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85065233205
ISSN
1741-7015
DOI
10.1186/s12916-019-1319-4
language
English
LU publication?
yes
id
e076091b-0aa5-4083-acf3-cccf70efd416
date added to LUP
2019-05-21 14:09:48
date last changed
2019-10-15 07:05:08
@article{e076091b-0aa5-4083-acf3-cccf70efd416,
  abstract     = {<p>Introduction: Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH. Methods: For this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific). Results: Obese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD- 6.4 ± 2.6; and non-ob/NAFLD- 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02-2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components. Conclusions: Increased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention.</p>},
  articleno    = {85},
  author       = {Barchetta, Ilaria and Enhörning, Sofia and Cimini, Flavia Agata and Capoccia, Danila and Chiappetta, Caterina and Di Cristofano, Claudio and Silecchia, Gianfranco and Leonetti, Frida and Melander, Olle and Cavallo, Maria Gisella},
  issn         = {1741-7015},
  keyword      = {Antidiuretic hormone,Copeptin,Fatty liver,Metabolic syndrome,NAFLD,NASH,Obesity,Vasopressin},
  language     = {eng},
  month        = {04},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Medicine},
  title        = {Elevated plasma copeptin levels identify the presence and severity of non-alcoholic fatty liver disease in obesity},
  url          = {http://dx.doi.org/10.1186/s12916-019-1319-4},
  volume       = {17},
  year         = {2019},
}