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Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Fatty Liver | Research

Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study

Authors: Hideki Shinoda, Yuya Watanabe, Kota Fukai, Kayoko Kasuya, Yuko Furuya, Shoko Nakazawa, Toru Honda, Takeshi Hayashi, Toru Nakagawa, Masayuki Tatemichi, Masaaki Korenaga

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Fib4 index (Fib4) is clinically used as a noninvasive marker of liver fibrosis. In this study, we aimed to preliminarily investigate whether Fib4 can be used to detect individuals who need assessment for alcoholic liver disease (ALD) in the general population by clarifying the detailed association of Fib4 with alcohol consumption and gamma-glutamyl transferase (GGT) among male workers.

Methods

We analyzed data sets on the comprehensive medical examinations of male workers as cross-sectional and retrospectively longitudinal studies. We enrolled 10 782 males (mean age: 52.2 ± 10.2 years) in FY2019 and 7845 males (mean follow-up: 12.6 ± 6.7 years) who could be consecutively followed up for 20 years from FY2000 to FY2019. Data were evaluated using logistic regression and COX proportional analysis.

Results

In the cross-sectional setting, the rate of Fib4 ≥ 2.67 in heavy drinkers (≥ 40 g of ethanol/day) was increased dose dependently in those over 65 years old, and that of body mass index ≥ 30 kg/m2 was increased in those over 60 years old, but not in those with fatty liver. The odds ratio (OR) (95% confidence interval [CI]) for heavy drinking was 4.30 (95% CI = 1.90–9.72), and GGT ≥ 200 IU/L was considerably high (OR = 29.05 [95% CI = 17.03–49.56]). In the longitudinal setting, heavy drinkers and those with GGT ≥ 200 IU/L at 10 years after the baseline showed an increased risk for Fib4 ≥ 2.67 (hazard ratio = 2.17 [95% CI = 1.58–2.98] and 7.65 [95% CI 5.26–11.12], respectively).

Conclusions

The development of Fib4 ≥ 2.67 after 10 years was associated with heavy alcohol drinking and GGT level ≥ 200 IU/L. Therefore, Fib4 combined with GGT could indicate high risk of ALD. However, clinical examinations and course observations are essentially needed.
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Literature
1.
go back to reference Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Mark SS, Torriani FJ, Dieterich DT, Thomas DL, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.CrossRef Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Mark SS, Torriani FJ, Dieterich DT, Thomas DL, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.CrossRef
2.
go back to reference Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol Hepatol. 2021;6(7):578–88.CrossRef Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol Hepatol. 2021;6(7):578–88.CrossRef
3.
go back to reference Balakrishnan M, Loomba R. The role of noninvasive tests for differentiating NASH From NAFL and diagnosing advanced fibrosis among patients with NAFLD. J Clin Gastroenterol. 2020;54(2):107–13.CrossRef Balakrishnan M, Loomba R. The role of noninvasive tests for differentiating NASH From NAFL and diagnosing advanced fibrosis among patients with NAFLD. J Clin Gastroenterol. 2020;54(2):107–13.CrossRef
4.
go back to reference Kechagias S, Ekstedt M, Simonsson C, Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones (Athens). 2022. Kechagias S, Ekstedt M, Simonsson C, Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones (Athens). 2022.
5.
go back to reference Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: a meta-analysis. Hepatology. 2017;66(5):1486–501.CrossRef Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: a meta-analysis. Hepatology. 2017;66(5):1486–501.CrossRef
6.
go back to reference Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF, Aboyans V, Adetokunboh O, Afshin A, Agrawal A, et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2017;390(10100):1151–210.CrossRef Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF, Aboyans V, Adetokunboh O, Afshin A, Agrawal A, et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2017;390(10100):1151–210.CrossRef
7.
go back to reference Sugiyama A, Kurisu A, E B, Ouoba S, Ko K, Rakhimov A, Akita T, Harakawa T, Sako T, Koshiyama M et al. Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups. BMC Gastroenterol. 2022, 22(1):241. Sugiyama A, Kurisu A, E B, Ouoba S, Ko K, Rakhimov A, Akita T, Harakawa T, Sako T, Koshiyama M et al. Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups. BMC Gastroenterol. 2022, 22(1):241.
8.
go back to reference Seitz HK, Bataller R, Cortez-Pinto H, Gao B, Gual A, Lackner C, Mathurin P, Mueller S, Szabo G, Tsukamoto H. Alcoholic liver disease. Nat Rev Dis Primers. 2018;4(1):16.CrossRef Seitz HK, Bataller R, Cortez-Pinto H, Gao B, Gual A, Lackner C, Mathurin P, Mueller S, Szabo G, Tsukamoto H. Alcoholic liver disease. Nat Rev Dis Primers. 2018;4(1):16.CrossRef
9.
go back to reference Kamper-Jørgensen M, Grønbaek M, Tolstrup J, Becker U. Alcohol and cirrhosis: dose–response or threshold effect? J Hepatol. 2004;41(1):25–30.CrossRef Kamper-Jørgensen M, Grønbaek M, Tolstrup J, Becker U. Alcohol and cirrhosis: dose–response or threshold effect? J Hepatol. 2004;41(1):25–30.CrossRef
10.
go back to reference Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med. 2004;38(5):613–9.CrossRef Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med. 2004;38(5):613–9.CrossRef
11.
go back to reference Popham RE, Schmidt W. Words and deeds: the validity of self-report data on alcohol consumption. J Stud Alcohol. 1981;42(3):355–68.CrossRef Popham RE, Schmidt W. Words and deeds: the validity of self-report data on alcohol consumption. J Stud Alcohol. 1981;42(3):355–68.CrossRef
12.
go back to reference Watson CG, Tilleskjor C, Hoodecheck-Schow EA, Pucel J, Jacobs L. Do alcoholics give valid self-reports? J Stud Alcohol. 1984;45(4):344–8.CrossRef Watson CG, Tilleskjor C, Hoodecheck-Schow EA, Pucel J, Jacobs L. Do alcoholics give valid self-reports? J Stud Alcohol. 1984;45(4):344–8.CrossRef
13.
go back to reference Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.CrossRef Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.CrossRef
14.
go back to reference Scouller K, Conigrave KM, Macaskill P, Irwig L, Whitfield JB. Should we use carbohydrate-deficient transferrin instead of gamma-glutamyltransferase for detecting problem drinkers? A systematic review and metaanalysis. Clin Chem. 2000;46(12):1894–902.CrossRef Scouller K, Conigrave KM, Macaskill P, Irwig L, Whitfield JB. Should we use carbohydrate-deficient transferrin instead of gamma-glutamyltransferase for detecting problem drinkers? A systematic review and metaanalysis. Clin Chem. 2000;46(12):1894–902.CrossRef
15.
go back to reference Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K. Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet. 2011;26(1):30–46.CrossRef Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K. Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet. 2011;26(1):30–46.CrossRef
16.
go back to reference Fukai K, Terauchi R, Noro T, Ogawa S, Watanabe T, Nakagawa T, Honda T, Watanabe Y, Furuya Y, Hayashi T, et al. Real-time risk score for glaucoma mass screening by spectral domain optical coherence tomography: development and validation. Transl Vis Sci Technol. 2022;11(8):8.CrossRef Fukai K, Terauchi R, Noro T, Ogawa S, Watanabe T, Nakagawa T, Honda T, Watanabe Y, Furuya Y, Hayashi T, et al. Real-time risk score for glaucoma mass screening by spectral domain optical coherence tomography: development and validation. Transl Vis Sci Technol. 2022;11(8):8.CrossRef
17.
go back to reference Honda T, Nakagawa T, Watanabe Y, Hayashi T, Nakano T, Horie S, Tatemichi M. Association between information and communication technology use and ocular axial length elongation among middle-aged male workers. Sci Rep. 2019;9(1):17489.CrossRef Honda T, Nakagawa T, Watanabe Y, Hayashi T, Nakano T, Horie S, Tatemichi M. Association between information and communication technology use and ocular axial length elongation among middle-aged male workers. Sci Rep. 2019;9(1):17489.CrossRef
18.
go back to reference Nakano T, Hayashi T, Nakagawa T, Honda T, Owada S, Endo H, Tatemichi M. Applicability of automatic spectral domain optical coherence tomography for glaucoma mass screening. Clin Ophthalmol. 2017;11:97–103.CrossRef Nakano T, Hayashi T, Nakagawa T, Honda T, Owada S, Endo H, Tatemichi M. Applicability of automatic spectral domain optical coherence tomography for glaucoma mass screening. Clin Ophthalmol. 2017;11:97–103.CrossRef
19.
go back to reference Nakano T, Hayashi T, Nakagawa T, Honda T, Owada S, Endo H, Tatemichi M. Increased incidence of visual field abnormalities as determined by frequency doubling technology perimetry in high computer users among Japanese workers: a retrospective cohort study. J Epidemiol. 2018;28(4):214–9.CrossRef Nakano T, Hayashi T, Nakagawa T, Honda T, Owada S, Endo H, Tatemichi M. Increased incidence of visual field abnormalities as determined by frequency doubling technology perimetry in high computer users among Japanese workers: a retrospective cohort study. J Epidemiol. 2018;28(4):214–9.CrossRef
20.
go back to reference Watanabe Y, Nakagawa T, Fukai K, Honda T, Furuya H, Hayashi T, Tatemichi M. Descriptive study of chest x-ray examination in mandatory annual health examinations at the workplace in Japan. PLoS ONE. 2022;17(1): e0262404.CrossRef Watanabe Y, Nakagawa T, Fukai K, Honda T, Furuya H, Hayashi T, Tatemichi M. Descriptive study of chest x-ray examination in mandatory annual health examinations at the workplace in Japan. PLoS ONE. 2022;17(1): e0262404.CrossRef
21.
go back to reference Fukai K, Kuwahara K, Chen S, Eguchi M, Kochi T, Kabe I, Mizoue T. The association of leisure-time physical activity and walking during commuting to work with depressive symptoms among Japanese workers: a cross-sectional study. J Occup Health. 2020;62(1): e12120.CrossRef Fukai K, Kuwahara K, Chen S, Eguchi M, Kochi T, Kabe I, Mizoue T. The association of leisure-time physical activity and walking during commuting to work with depressive symptoms among Japanese workers: a cross-sectional study. J Occup Health. 2020;62(1): e12120.CrossRef
22.
go back to reference Watanabe S, Hashimoto E, Ikejima K, Uto H, Ono M, Sumida Y, Seike M, Takei Y, Takehara T, Tokushige K, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol. 2015;50(4):364–77.CrossRef Watanabe S, Hashimoto E, Ikejima K, Uto H, Ono M, Sumida Y, Seike M, Takei Y, Takehara T, Tokushige K, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol. 2015;50(4):364–77.CrossRef
23.
go back to reference Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–12.CrossRef Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–12.CrossRef
24.
go back to reference Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, Zelber-Sagi S, Wai-Sun Wong V, Dufour JF, Schattenberg JM, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73(1):202–9.CrossRef Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, Zelber-Sagi S, Wai-Sun Wong V, Dufour JF, Schattenberg JM, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73(1):202–9.CrossRef
25.
go back to reference Tanaka J, Kurisu A, Ohara M, Ouoba S, Ohisa M, Sugiyama A, Wang ML, Hiebert L, Kanto T, Akita T. Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: a simulation study. Lancet Reg Health West Pac. 2022;22: 100428.CrossRef Tanaka J, Kurisu A, Ohara M, Ouoba S, Ohisa M, Sugiyama A, Wang ML, Hiebert L, Kanto T, Akita T. Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: a simulation study. Lancet Reg Health West Pac. 2022;22: 100428.CrossRef
26.
go back to reference Ma Q, Liao X, Shao C, Lin Y, Wu T, Sun Y, Feng ST, Ye J, Zhong B. Normalization of γ-glutamyl transferase levels is associated with better metabolic control in individuals with nonalcoholic fatty liver disease. BMC Gastroenterol. 2021;21(1):215.CrossRef Ma Q, Liao X, Shao C, Lin Y, Wu T, Sun Y, Feng ST, Ye J, Zhong B. Normalization of γ-glutamyl transferase levels is associated with better metabolic control in individuals with nonalcoholic fatty liver disease. BMC Gastroenterol. 2021;21(1):215.CrossRef
27.
go back to reference Kunutsor SK, Apekey TA, Seddoh D. Gamma glutamyltransferase and metabolic syndrome risk: a systematic review and dose-response meta-analysis. Int J Clin Pract. 2015;69(1):136–44.CrossRef Kunutsor SK, Apekey TA, Seddoh D. Gamma glutamyltransferase and metabolic syndrome risk: a systematic review and dose-response meta-analysis. Int J Clin Pract. 2015;69(1):136–44.CrossRef
28.
go back to reference Kim YG, Han K, Jeong JH, Roh SY, Choi YY, Min K, Shim J, Choi JI, Kim YH. Metabolic syndrome, gamma-glutamyl transferase, and risk of sudden cardiac death. J Clin Med. 2022; 11(7). Kim YG, Han K, Jeong JH, Roh SY, Choi YY, Min K, Shim J, Choi JI, Kim YH. Metabolic syndrome, gamma-glutamyl transferase, and risk of sudden cardiac death. J Clin Med. 2022; 11(7).
29.
go back to reference Ho FK, Ferguson LD, Celis-Morales CA, Gray SR, Forrest E, Alazawi W, Gill JM, Katikireddi SV, Cleland JG, Welsh P, et al. Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: a prospective cohort study in the UK Biobank. EClinicalMedicine. 2022;48: 101435.CrossRef Ho FK, Ferguson LD, Celis-Morales CA, Gray SR, Forrest E, Alazawi W, Gill JM, Katikireddi SV, Cleland JG, Welsh P, et al. Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: a prospective cohort study in the UK Biobank. EClinicalMedicine. 2022;48: 101435.CrossRef
30.
go back to reference Li S, Wang A, Tian X, Zuo Y, Meng X, Zhang Y. Elevated gamma-glutamyl transferase levels are associated with stroke recurrence after acute ischemic stroke or transient ischemic attack. CNS Neurosci Ther. 2022. Li S, Wang A, Tian X, Zuo Y, Meng X, Zhang Y. Elevated gamma-glutamyl transferase levels are associated with stroke recurrence after acute ischemic stroke or transient ischemic attack. CNS Neurosci Ther. 2022.
31.
go back to reference Ikeda Y, Taniguchi N. Gene expression of gamma-glutamyltranspeptidase. Methods Enzymol. 2005;401:408–25.CrossRef Ikeda Y, Taniguchi N. Gene expression of gamma-glutamyltranspeptidase. Methods Enzymol. 2005;401:408–25.CrossRef
32.
go back to reference Ishii H, Ebihara Y, Okuno F, Munakata Y, Takagi T, Arai M, Shigeta S, Tsuchiya M. Gamma-Glutamyl transpeptidase activity in liver of alcoholics and its localization. Alcohol Clin Exp Res. 1986;10(1):81–5.CrossRef Ishii H, Ebihara Y, Okuno F, Munakata Y, Takagi T, Arai M, Shigeta S, Tsuchiya M. Gamma-Glutamyl transpeptidase activity in liver of alcoholics and its localization. Alcohol Clin Exp Res. 1986;10(1):81–5.CrossRef
33.
go back to reference Li H, Liu R, Li J, Li J, Wu H, Wang G, Li Z, Li D. Prognostic significance of gamma-glutamyl transpeptidase to albumin ratio in patients with intrahepatic cholangiocarcinoma after hepatectomy. J Cell Mol Med. 2022;26(11):3196–202.CrossRef Li H, Liu R, Li J, Li J, Wu H, Wang G, Li Z, Li D. Prognostic significance of gamma-glutamyl transpeptidase to albumin ratio in patients with intrahepatic cholangiocarcinoma after hepatectomy. J Cell Mol Med. 2022;26(11):3196–202.CrossRef
34.
go back to reference Deprince A, Haas JT, Staels B. Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol Metab. 2020;42: 101092.CrossRef Deprince A, Haas JT, Staels B. Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol Metab. 2020;42: 101092.CrossRef
35.
go back to reference Wang Y, Shen W, Huang F, Yu C, Xi L, Gao J, Yin M, Liu X, Lin J, Liu L, et al. HDL-C levels added to the MELD score improves 30-day mortality prediction in Asian patients with cirrhosis. J Int Med Res. 2022;50(7):3000605221109385.CrossRef Wang Y, Shen W, Huang F, Yu C, Xi L, Gao J, Yin M, Liu X, Lin J, Liu L, et al. HDL-C levels added to the MELD score improves 30-day mortality prediction in Asian patients with cirrhosis. J Int Med Res. 2022;50(7):3000605221109385.CrossRef
36.
go back to reference Ren XY, Shi D, Ding J, Cheng ZY, Li HY, Li JS, Pu HQ, Yang AM, He CL, Zhang JP, et al. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study. Lipids Health Dis. 2019;18(1):47.CrossRef Ren XY, Shi D, Ding J, Cheng ZY, Li HY, Li JS, Pu HQ, Yang AM, He CL, Zhang JP, et al. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study. Lipids Health Dis. 2019;18(1):47.CrossRef
37.
go back to reference Liu Z, He H, Dai Y, Yang L, Liao S, An Z, Li S. Comparison of the diagnostic value between triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio in metabolic-associated fatty liver disease patients: a retrospective cross-sectional study. Lipids Health Dis. 2022;21(1):55.CrossRef Liu Z, He H, Dai Y, Yang L, Liao S, An Z, Li S. Comparison of the diagnostic value between triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio in metabolic-associated fatty liver disease patients: a retrospective cross-sectional study. Lipids Health Dis. 2022;21(1):55.CrossRef
38.
go back to reference Xing Y, Chen J, Liu J, Ma H. Associations between GGT/HDL and MAFLD: a cross-sectional study. Diabetes Metab Syndr Obes. 2022;15:383–94.CrossRef Xing Y, Chen J, Liu J, Ma H. Associations between GGT/HDL and MAFLD: a cross-sectional study. Diabetes Metab Syndr Obes. 2022;15:383–94.CrossRef
39.
go back to reference Berger D, Williams EC, Bryson CL, Rubinsky AD, Bradley KA. Alcohol questionnaires and HDL: screening scores as scaled markers of alcohol consumption. Alcohol. 2013;47(6):439–45.CrossRef Berger D, Williams EC, Bryson CL, Rubinsky AD, Bradley KA. Alcohol questionnaires and HDL: screening scores as scaled markers of alcohol consumption. Alcohol. 2013;47(6):439–45.CrossRef
40.
go back to reference Høiseth G, Hilberg T, Trydal T, Husa A, Vindenes V, Bogstrand ST. The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C. Basic Clin Pharmacol Toxicol. 2022;130(1):182–90.CrossRef Høiseth G, Hilberg T, Trydal T, Husa A, Vindenes V, Bogstrand ST. The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C. Basic Clin Pharmacol Toxicol. 2022;130(1):182–90.CrossRef
41.
go back to reference Sillanaukee P, Massot N, Jousilahti P, Vartiainen E, Sundvall J, Olsson U, Poikolainen K, Pönniö M, Allen JP, Alho H. Dose response of laboratory markers to alcohol consumption in a general population. Am J Epidemiol. 2000;152(8):747–51.CrossRef Sillanaukee P, Massot N, Jousilahti P, Vartiainen E, Sundvall J, Olsson U, Poikolainen K, Pönniö M, Allen JP, Alho H. Dose response of laboratory markers to alcohol consumption in a general population. Am J Epidemiol. 2000;152(8):747–51.CrossRef
42.
go back to reference Kiefer F, Batra A, Petersen KU, Ardern IS, Tananska D, Bischof G, Funke W, Lindenmeyer J, Mueller S, Preuss UW, et al. German guidelines on screening, diagnosis, and treatment of alcohol use disorders: update 2021. Eur Addict Res. 2022;28(4):309–22.CrossRef Kiefer F, Batra A, Petersen KU, Ardern IS, Tananska D, Bischof G, Funke W, Lindenmeyer J, Mueller S, Preuss UW, et al. German guidelines on screening, diagnosis, and treatment of alcohol use disorders: update 2021. Eur Addict Res. 2022;28(4):309–22.CrossRef
43.
go back to reference New guidelines for the diagnosis and treatment of alcohol and drug use disorders Shinko Igaku Shuppansha.; 2018. New guidelines for the diagnosis and treatment of alcohol and drug use disorders Shinko Igaku Shuppansha.; 2018.
44.
go back to reference Miyata H, Takahashi M, Murai Y, Tsuneyoshi K, Hayashi T, Meulien D, Sørensen P, Higuchi S. Nalmefene in alcohol-dependent patients with a high drinking risk: randomized controlled trial. Psychiatry Clin Neurosci. 2019;73(11):697–706.CrossRef Miyata H, Takahashi M, Murai Y, Tsuneyoshi K, Hayashi T, Meulien D, Sørensen P, Higuchi S. Nalmefene in alcohol-dependent patients with a high drinking risk: randomized controlled trial. Psychiatry Clin Neurosci. 2019;73(11):697–706.CrossRef
Metadata
Title
Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study
Authors
Hideki Shinoda
Yuya Watanabe
Kota Fukai
Kayoko Kasuya
Yuko Furuya
Shoko Nakazawa
Toru Honda
Takeshi Hayashi
Toru Nakagawa
Masayuki Tatemichi
Masaaki Korenaga
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Fatty Liver
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-022-00976-6

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