Skip to main content
Top
Published in: BMC Gastroenterology 1/2019

Open Access 01-12-2019 | Fatty Liver | Research article

A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels

Authors: Pengzi Zhang, Wenhuan Feng, Xuehui Chu, Xitai Sun, Dalong Zhu, Yan Bi

Published in: BMC Gastroenterology | Issue 1/2019

Login to get access

Abstract

Backgrounds

To investigate the value of prolactin (PRL) in diagnosing non-alcoholic fatty liver disease (NAFLD).

Methods

Metabolic parameters and serum PRL levels were measured in 452 males and 421 females, who were randomized to the estimation or the validation group as a 1:1 ratio. Hepatic steatosis was diagnosed via abdominal ultrasound. Variables that significantly associated with NAFLD in univariate analysis were included in multiple logistic regression. We used the receiver operator characteristic (ROC) curves to test the model performance. Besides, 147 patients underwent metabolic and liver biopsy were analyzed to validate the diagnostic value of this model.

Results

Body mass index, alanine aminotransferase, prolactin, high density lipoprotein cholesterol and HbA1c were included into models. In males, the area under ROC curve (AUC) was 0.86 (95%CI: 0.82–0.91) for the validation group. With two cut-off points (− 0.79 and 1.71), the sensitivity and specificity for predicting NALFD was 95.2 and 91.1% in the validation group, respectively. In females, the AUC was 0.82 (95%CI: 0.76–0.88) for the validation group. With two cut-off points (− 0.68 and 2.16), the sensitivity and specificity for predicting NALFD was 97.1 and 91.4% in the validation group, respectively. In subjects with liver pathology, the AUC was higher than that of fatty liver index. A positive correlation between the scores of the model and the severities of NAFLD was observed. Importantly, we demonstrated a potential value of this model in predicting nonalcoholic steatohepatitis.

Conclusion

We established a mathematic model that can conveniently and effectively diagnose the existence and severities of NAFLD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10(6):330–44.PubMed Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10(6):330–44.PubMed
2.
go back to reference 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(1):73–84.PubMed 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(1):73–84.PubMed
3.
go back to reference Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617–49.PubMed Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617–49.PubMed
4.
go back to reference Hu KC, Wang HY, Liu SC, Liu CC, Hung CL, Bair MJ, Liu CJ, Wu MS, Shih SC. Nonalcoholic fatty liver disease: updates in noninvasive diagnosis and correlation with cardiovascular disease. World J Gastroenterol. 2014;20(24):7718–29.PubMedPubMedCentral Hu KC, Wang HY, Liu SC, Liu CC, Hung CL, Bair MJ, Liu CJ, Wu MS, Shih SC. Nonalcoholic fatty liver disease: updates in noninvasive diagnosis and correlation with cardiovascular disease. World J Gastroenterol. 2014;20(24):7718–29.PubMedPubMedCentral
5.
go back to reference Yadav D, Choi E, Ahn SV, Koh SB, Sung KC, Kim JY, Huh JH. Fatty liver index as a simple predictor of incident diabetes from the KoGES-ARIRANG study. Medicine (Baltimore). 2016;95(31):e4447. Yadav D, Choi E, Ahn SV, Koh SB, Sung KC, Kim JY, Huh JH. Fatty liver index as a simple predictor of incident diabetes from the KoGES-ARIRANG study. Medicine (Baltimore). 2016;95(31):e4447.
6.
go back to reference European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402.
7.
go back to reference Shao S, Yao Z, Lu J, Song Y, He Z, Yu C, Zhou X, Zhao L, Zhao J, Gao L. Ablation of prolactin receptor increases hepatic triglyceride accumulation. Biochem Biophys Res Commun. 2018;498(3):693–9.PubMed Shao S, Yao Z, Lu J, Song Y, He Z, Yu C, Zhou X, Zhao L, Zhao J, Gao L. Ablation of prolactin receptor increases hepatic triglyceride accumulation. Biochem Biophys Res Commun. 2018;498(3):693–9.PubMed
8.
go back to reference Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol. 2009;50(1):204–10.PubMed Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol. 2009;50(1):204–10.PubMed
9.
go back to reference Haring R, Hannemann A, John U, Radke D, Nauck M, Wallaschofski H, Owen L, Adaway J, Keevil BG, Brabant G. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2012;97(2):408–15.PubMed Haring R, Hannemann A, John U, Radke D, Nauck M, Wallaschofski H, Owen L, Adaway J, Keevil BG, Brabant G. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2012;97(2):408–15.PubMed
10.
go back to reference Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.PubMedPubMedCentral Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.PubMedPubMedCentral
11.
go back to reference Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.PubMed Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.PubMed
12.
go back to reference Roelfsema F, Pijl H, Keenan DM, Veldhuis JD. Prolactin secretion in healthy adults is determined by gender, age and body mass index. PLoS One. 2012;7(2):e31305.PubMedPubMedCentral Roelfsema F, Pijl H, Keenan DM, Veldhuis JD. Prolactin secretion in healthy adults is determined by gender, age and body mass index. PLoS One. 2012;7(2):e31305.PubMedPubMedCentral
13.
go back to reference Korevaar DA, Cohen JF, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Moher D, de Vet HCW, Altman DG, et al. Updating standards for reporting diagnostic accuracy: the development of STARD 2015. Res Integr Peer Rev. 2016;1:7.PubMedPubMedCentral Korevaar DA, Cohen JF, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Moher D, de Vet HCW, Altman DG, et al. Updating standards for reporting diagnostic accuracy: the development of STARD 2015. Res Integr Peer Rev. 2016;1:7.PubMedPubMedCentral
14.
go back to reference Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform. 2014;48:193–204.PubMed Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform. 2014;48:193–204.PubMed
15.
go back to reference Pencina MJ, D'Agostino RB, D’Agostino RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157–72.PubMed Pencina MJ, D'Agostino RB, D’Agostino RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157–72.PubMed
16.
go back to reference Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PMM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol. 2003;56(11):1129–35.PubMed Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PMM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol. 2003;56(11):1129–35.PubMed
17.
go back to reference Delong ER, Delong DM, Clarkepearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45.PubMed Delong ER, Delong DM, Clarkepearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45.PubMed
18.
go back to reference Tanner MJ, Hadlow NC, Wardrop R. Variation of female prolactin levels with menopausal status and phase of menstrual cycle. Aust N Z J Obstet Gynaecol. 2011;51(4):321–4.PubMed Tanner MJ, Hadlow NC, Wardrop R. Variation of female prolactin levels with menopausal status and phase of menstrual cycle. Aust N Z J Obstet Gynaecol. 2011;51(4):321–4.PubMed
19.
go back to reference Kerr KF, Bansal A, Pepe MS. Further insight into the incremental value of new markers: the interpretation of performance measures and the importance of clinical context. Am J Epidemiol. 2012;176(6):482–7.PubMedPubMedCentral Kerr KF, Bansal A, Pepe MS. Further insight into the incremental value of new markers: the interpretation of performance measures and the importance of clinical context. Am J Epidemiol. 2012;176(6):482–7.PubMedPubMedCentral
20.
go back to reference Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1):S47–64.PubMed Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1):S47–64.PubMed
21.
go back to reference Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17(6):510–9.PubMed Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17(6):510–9.PubMed
22.
go back to reference Yu J, Xiao F, Zhang Q, Liu B, Guo Y, Lv Z, Xia T, Chen S, Li K, Du Y, et al. PRLR regulates hepatic insulin sensitivity in mice via STAT5. Diabetes. 2013;62(9):3103–13.PubMedPubMedCentral Yu J, Xiao F, Zhang Q, Liu B, Guo Y, Lv Z, Xia T, Chen S, Li K, Du Y, et al. PRLR regulates hepatic insulin sensitivity in mice via STAT5. Diabetes. 2013;62(9):3103–13.PubMedPubMedCentral
23.
go back to reference Yu AS, Keeffe EB. Elevated AST or ALT to nonalcoholic fatty liver disease: accurate predictor of disease prevalence? Am J Gastroenterol. 2003;98(5):955–6.PubMed Yu AS, Keeffe EB. Elevated AST or ALT to nonalcoholic fatty liver disease: accurate predictor of disease prevalence? Am J Gastroenterol. 2003;98(5):955–6.PubMed
24.
go back to reference Loomba R, Sanyal AJ, Kowdley KV, Terrault NA, Chalasani N, Abdelmalek MF, Mccullough AJ, Shringarpure R, Ferguson B, Lee L. Factors associated with histologic response in adult patients with nonalcoholic Steatohepatitis. Gastroenterology. 2019;156(1):88-95. Loomba R, Sanyal AJ, Kowdley KV, Terrault NA, Chalasani N, Abdelmalek MF, Mccullough AJ, Shringarpure R, Ferguson B, Lee L. Factors associated with histologic response in adult patients with nonalcoholic Steatohepatitis. Gastroenterology. 2019;156(1):88-95.
25.
go back to reference Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S1-S2. Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S1-S2.
26.
go back to reference Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly P. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225–68.PubMed Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly P. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225–68.PubMed
27.
go back to reference Bernard V, Young J, Chanson P, Binart N. New insights in prolactin: pathological implications. Nat Rev Endocrinol. 2015;11(5):265–75.PubMed Bernard V, Young J, Chanson P, Binart N. New insights in prolactin: pathological implications. Nat Rev Endocrinol. 2015;11(5):265–75.PubMed
28.
go back to reference Zhang P, Ge Z, Wang H, Feng W, Sun X, Chu X, Jiang C, Wang Y, Zhu D, Bi Y. Prolactin improves hepatic steatosis via CD36 pathway. J Hepatol. 2018;68(6):1247-55. Zhang P, Ge Z, Wang H, Feng W, Sun X, Chu X, Jiang C, Wang Y, Zhu D, Bi Y. Prolactin improves hepatic steatosis via CD36 pathway. J Hepatol. 2018;68(6):1247-55.
29.
go back to reference Corona G, Wu FC, Rastrelli G, Lee DM, Forti G, O'Connor DB, O'Neill TW, Pendleton N, Bartfai G, Boonen S, et al. Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle-aged and elderly men: the European male aging study (EMAS). J Sex Med. 2014;11(1):240–53.PubMed Corona G, Wu FC, Rastrelli G, Lee DM, Forti G, O'Connor DB, O'Neill TW, Pendleton N, Bartfai G, Boonen S, et al. Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle-aged and elderly men: the European male aging study (EMAS). J Sex Med. 2014;11(1):240–53.PubMed
30.
go back to reference Bertolotti M, Lonardo A, Mussi C, Baldelli E, Pellegrini E, Ballestri S, Romagnoli D, Loria P. Nonalcoholic fatty liver disease and aging: epidemiology to management. World J Gastroenterol. 2014;20(39):14185–204.PubMedPubMedCentral Bertolotti M, Lonardo A, Mussi C, Baldelli E, Pellegrini E, Ballestri S, Romagnoli D, Loria P. Nonalcoholic fatty liver disease and aging: epidemiology to management. World J Gastroenterol. 2014;20(39):14185–204.PubMedPubMedCentral
31.
go back to reference Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240(4857):1285–93.PubMed Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240(4857):1285–93.PubMed
32.
go back to reference Koehler EM, Schouten JN, Hansen BE, Hofman A, Stricker BH, Janssen HL. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol. 2013;11(9):1201–4.PubMed Koehler EM, Schouten JN, Hansen BE, Hofman A, Stricker BH, Janssen HL. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol. 2013;11(9):1201–4.PubMed
33.
go back to reference Carvalhana S, Leitao J, Alves AC, Bourbon M, Cortez-Pinto H. How good is controlled attenuation parameter and fatty liver index for assessing liver steatosis in general population: correlation with ultrasound. Liver Int. 2014;34(6):e111–7.PubMed Carvalhana S, Leitao J, Alves AC, Bourbon M, Cortez-Pinto H. How good is controlled attenuation parameter and fatty liver index for assessing liver steatosis in general population: correlation with ultrasound. Liver Int. 2014;34(6):e111–7.PubMed
34.
go back to reference Wang J, Xu C, Xun Y, Lu Z, Shi J, Yu C, Li Y. ZJU index: a novel model for predicting nonalcoholic fatty liver disease in a Chinese population. Sci Rep. 2015;5:16494.PubMedPubMedCentral Wang J, Xu C, Xun Y, Lu Z, Shi J, Yu C, Li Y. ZJU index: a novel model for predicting nonalcoholic fatty liver disease in a Chinese population. Sci Rep. 2015;5:16494.PubMedPubMedCentral
35.
go back to reference Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwandertetri BA, Serfaty L, Negro F, Caldwell SH. Diagnostic MODALITIES FOR NON-ALCOHOLIC FATTY LIVER Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH) and Associated Fibrosis. Hepatology. 2017;68(1):349-60. Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwandertetri BA, Serfaty L, Negro F, Caldwell SH. Diagnostic MODALITIES FOR NON-ALCOHOLIC FATTY LIVER Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH) and Associated Fibrosis. Hepatology. 2017;68(1):349-60.
36.
go back to reference Gaidos JK, Hillner BE, Sanyal AJ. A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int. 2008;28(5):650–8.PubMed Gaidos JK, Hillner BE, Sanyal AJ. A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int. 2008;28(5):650–8.PubMed
Metadata
Title
A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels
Authors
Pengzi Zhang
Wenhuan Feng
Xuehui Chu
Xitai Sun
Dalong Zhu
Yan Bi
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Fatty Liver
Published in
BMC Gastroenterology / Issue 1/2019
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-019-1120-z

Other articles of this Issue 1/2019

BMC Gastroenterology 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.