Serum C16:1n7/C16:0 ratio as a diagnostic marker for non-alcoholic steatohepatitis.
fatty acid
non-alcoholic fatty liver disease
palmitic acid
palmitoleic acid
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
30
04
2018
revised:
28
02
2019
accepted:
04
03
2019
pubmed:
14
3
2019
medline:
6
5
2020
entrez:
14
3
2019
Statut:
ppublish
Résumé
Accurate diagnosis of non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver disease (NAFLD) is clinically important. Therefore, there is a need for easier ways of diagnosing NASH. In this study, we investigated the serum fatty acid composition and evaluated the possibility of using the serum fatty acid composition as a diagnostic marker of NASH. The subjects were 78 NAFLD patients (non-alcoholic fatty liver [NAFL]: 30, NASH: 48) and 24 healthy individuals. Fatty acids extracted from the liver tissue and serum were identified and quantified by gas chromatography. In addition, we evaluated the relationship between serum and liver tissue fatty acid composition, patient background, and liver histology. The diagnostic performance of NASH was evaluated by calculating the area under the receiver operating characteristic (AUROC). The results of the fatty acid analysis showed the C16:1n7/C16:0 ratio to have the strongest correlation between serum and liver tissue (r = 0.865, P < 0.0001). The serum C16:1n7/C16:0 ratio in the NASH group was higher compared with that in the NAFL group (P = 0.0007). Evaluation of the association of the serum C16:1n7/C16:0 ratio with liver histology revealed significant correlation with lobular inflammation score, ballooning score, and fibrosis score. The AUROC for predicting NASH in all NAFLD patients was 0.7097. The AUROC was nearly equivalent even when the study subjects were restricted to patients with a fibrosis score ≤ 2 only (AUROC 0.6917). Measuring the serum C16:1n7/C16:0 ratio may be an effective non-invasive method for diagnosing NASH, particularly in its early stages.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Accurate diagnosis of non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver disease (NAFLD) is clinically important. Therefore, there is a need for easier ways of diagnosing NASH. In this study, we investigated the serum fatty acid composition and evaluated the possibility of using the serum fatty acid composition as a diagnostic marker of NASH.
METHODS
METHODS
The subjects were 78 NAFLD patients (non-alcoholic fatty liver [NAFL]: 30, NASH: 48) and 24 healthy individuals. Fatty acids extracted from the liver tissue and serum were identified and quantified by gas chromatography. In addition, we evaluated the relationship between serum and liver tissue fatty acid composition, patient background, and liver histology. The diagnostic performance of NASH was evaluated by calculating the area under the receiver operating characteristic (AUROC).
RESULTS
RESULTS
The results of the fatty acid analysis showed the C16:1n7/C16:0 ratio to have the strongest correlation between serum and liver tissue (r = 0.865, P < 0.0001). The serum C16:1n7/C16:0 ratio in the NASH group was higher compared with that in the NAFL group (P = 0.0007). Evaluation of the association of the serum C16:1n7/C16:0 ratio with liver histology revealed significant correlation with lobular inflammation score, ballooning score, and fibrosis score. The AUROC for predicting NASH in all NAFLD patients was 0.7097. The AUROC was nearly equivalent even when the study subjects were restricted to patients with a fibrosis score ≤ 2 only (AUROC 0.6917).
CONCLUSION
CONCLUSIONS
Measuring the serum C16:1n7/C16:0 ratio may be an effective non-invasive method for diagnosing NASH, particularly in its early stages.
Substances chimiques
Biomarkers
0
Fatty Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1829-1835Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology of Japan
Informations de copyright
© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Références
Kojima S, Watanabe N, Numata M, Ogawa T, Matsuzaki S. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J. Gastroenterol. 2003; 38: 954-961.
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment. Pharmacol. Ther. 2011; 34: 274-285.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84.
Adams LA, Lymp JF, St Sauver J et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: 113-121.
Rafiq N, Bai C, Fang Y et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin. Gastroenterol. Hepatol. 2009; 7: 234-238.
Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-1419.
Ratziu V, Charlotte F, Heurtier A et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898-1906.
Younossi ZM, Gramlich T, Liu YC et al. Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod. Pathol. 1998; 11: 560-565.
Merriman RB, Ferrell LD, Patti MG et al. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology 2006; 44: 874-880.
Bravo AA, Sheth SG, Chopra S. Liver biopsy. N. Engl. J. Med. 2001; 344: 495-500.
Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 2007; 46: 582-589.
Yamaguchi K, Yang L, McCall S et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 2007; 45: 1366-1374.
Yamada K, Mizukoshi E, Sunagozaka H et al. Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis. Liver Int. 2015; 35: 582-590.
Puri P, Wiest MM, Cheung O et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009; 50: 1827-1838.
Zhang J, Zhao Y, Xu C et al. Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study. Sci. Rep. 2014; 4: 5832.
Wang S, Ma A, Song S et al. Fasting serum free fatty acid composition, waist/hip ratio and insulin activity in essential hypertensive patients. Hypertens. Res. 2008; 31: 623-632.
Hua MC, Su HM, Yao TC et al. Alternation of plasma fatty acids composition and desaturase activities in children with liver steatosis. PLoS ONE 2017; 31: e0182277.
Tomita K, Teratani T, Yokoyama H et al. Plasma free myristic acid proportion is a predictor of nonalcoholic steatohepatitis. Dig. Dis. Sci. 2011; 56: 3045-3052.
Wang XH, Li CY, Muhammad I, Zhang XY. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet. Environ. Toxicol. Pharmacol. 2016; 44: 140-150.
Kotronen A, Seppänen-Laakso T, Westerbacka J et al. Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum. Obesity (Silver Spring) 2010; 18: 937-944.
Kleiner DE, Brunt EM, Van Natta M et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321.
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology 2012; 142: 711-725 e6.
Ma C, Kesarwala AH, Eggert T et al. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature 2016; 531: 253-257.
Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-2023.
Chitturi S, Abeygunasekera S, Farrell GC et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002; 35: 373-379.
Kowdley KV, Belt P, Wilson LA et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2012; 55: 77-85.
Sumida Y, Yoneda M, Hyogo H et al. A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J. Gastroenterol. 2011; 46: 257-268.
Shah AG, Lydecker A, Murray K et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2009; 7: 1104-1112.
Wong VW, Vergniol J, Wong GL et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462.
Angulo P, Kleiner DE, Dam-Larsen S et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2015; 149: 389-397 e10.
Seko Y, Sumida Y, Tanaka S et al. Predictors of malignancies and overall mortality in Japanese patients with biopsy-proven non-alcoholic fatty liver disease. Hepatol. Res. 2015; 45: 728-738.
Wong VW, Chitturi S, Wong GL, Yu J, Chan HL, Farrell GC. Pathogenesis and novel treatment options for non-alcoholic steatohepatitis. Lancet Gastroenterol. Hepatol. 2016; 1: 56-67.
Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J. Hepatol. 2009; 51: 371-379.