Fon Tacer K, Rozman D. Nonalcoholic fatty liver disease: focus on lipoprotein and
lipid deregulation. Journal of Lipids 2011;1-14.
Hamaguchi M, Takeda N, Kojima T, et al. Identification of individuals with nonalcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome.
World J Gastroenterol 2012; 18: 1508-16.
Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of
nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan:
a multicenter large retrospective study. J Gastroenterol 2012;47:586-95.
Williams C, Stengel J, Asike M, et al. Prevalence of Nonalcoholic Fatty Liver Disease
and Nonalcoholic Steatohepatitis Among a Largely Middle-Aged Population Utilizing
Ultrasound and Liver Biopsy: A Prospective Study. Gastroenterology 2011;140:12431.
Younossi ZM, Koenig AB, Abdelatif D, et al. Global Epidemiology of Nonalcoholic
Fatty Liver Disease—Meta-Analytic Assessment of Prevalence, Incidence, and
Outcomes. Hepatology 2016;64:73-84.
Enomoto H, Ueno Y, Hiasa Y, et al. Transition in the Etiology of Liver Cirrhosis in
Japan: A Nationwide Survey. J Gastroenterol 2020;55:353-62.
Kojima H, Sakurai S, Uemura M, et al. Mitochondorial abnormality and oxidative
stress in nonalcoholic steatohepatitis. Alcohol Clin Exp Res 2007;31:S61-6.
El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease
and hepatocellular carcinoma. Gastroenterology 2004;126:460-8.
日本消化器病学会・日本肝臓学会編. NAFLD/NASH 診療ガイドライン 2020
(改訂第 2 版)
.南江堂.東京.2020.
10
Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of nonalcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-
90
controlled phase 3 trial. Lancet 2019;394:2184-96.
11
Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous
Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021;384:1113-24.
12
Le P, Chaitoff A, Rothberg MB, et al. Trends in pioglitazone use among U.S. adults
with type 2 diabetes and suspected nonalcoholic fatty liver disease. Expert Opin
2022;29:205-8.
13
Adams LA, Anstee, QM, Tilg H, et al. Non-alcoholic fatty liver disease and its
relationship with cardiovascular disease and other extrahepatic diseases. Gut
2017;66:1138-53.
14
Hamaguchi M, Kojima T, Takeda N, et al. Nonalcoholic Fatty Liver Disease Is a
Novel Predictor of Cardiovascular Disease. World J Gastroenterol 2007;13:1579-84.
15
Haring R, Wallaschofski H, Nauck M, et al.
Ultrasonographic Hepatic Steatosis
Increases Prediction of Mortality Risk From Elevated Serum Gamma-Glutamyl
Transpeptidase Levels. Hepatology 2009;50:1403-11.
16
Targher G., Bertolini, L., Padovani, R., Rodella, S., Zoppini, G., Zenari, L., Cigolini,
M., Falezza, G., Arcaro, G. Relations Between Carotid Artery Wall Thickness and
Liver Histology in Subjects With Nonalcoholic Fatty Liver Disease. Diabetes Care
2006;29(6):1325-30.
17
Ismaiel A, Leucuta DC, Popa SL, et al. Noninvasive biomarkers in predicting
nonalcoholic steatohepatitis and assessing liver fibrosis: systematic review and metaanalysis. Panminerva Med. 2021;63:508-18.
18
Wong VWS, Adams LA, de Lédinghen V, et al. Noninvasive biomarkers in NAFLD
and NASH - current progress and future promise. Nat Rev Gastroenterol Hepatol.
2018;25:461-78.
19
Sesti G, Sciacqua A, Fiorentino TV, et al. Association between noninvasive fibrosis
markers and cardio-vascular organ damage among adults with hepatic steatosis. PLoS
ONE. 2014;9:e104941.
20
Pais R, Redheuil A, Cluzel P, et al. Relationship Among Fatty Liver, Specific and
91
Multiple-Site Atherosclerosis, and 10-Year Framingham Score. Hepatology.
2019;69:1453-63.
21
Cicero AFG, Gitto S, Fogacci F, et al. Fatty liver index is associated to pulse wave
velocity in healthy subjects: Data from the Brisighella Heart Study. Eur J of Inter Med.
2018;53:29-33.
22
Targher G, Bertolini L, Rodella S, et al. Non-alcoholic Fatty Liver Disease Is
Independently Associated With an Increased Prevalence of Chronic Kidney Disease
and Proliferative/Laser-Treated Retinopathy in Type 2 Diabetic Patients. Diabetologia
2008;51:444-50.
23
Pan L, Zhang H, Huang Z, et al. Intrahepatic Triglyceride Content Is Independently
Associated With Chronic Kidney Disease in Obese Adults: A Cross-Sectional Study.
Metabolism 2015;64:1077-85.
24
Yasui K, Sumida Y, Mori Y, et al. Nonalcoholic Steatohepatitis and Increased Risk of
Chronic Kidney Disease. 2011;60:735-9.
25
Targher G, Bertolini L, Rodella S, et al. Relationship Between Kidney Function and
Liver Histology in Subjects With Nonalcoholic Steatohepatitis. Clin J Am Soc
Nephrol 2010;5:2166-71.
26
Sesti G, Fiorentino TV, Arturi F, et al. Association Between Noninvasive Fibrosis
Markers and Chronic Kidney Disease Among Adults With Nonalcoholic Fatty Liver
Disease. PLoS One 2014;9:e88569.
27
Targher G, Bertolini L, Rodella S, et al. Relationship between kidney function and
liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol.
2010;5:2166-71.
28
Takahashi S, Tanaka M, Furuhashi M, et al. Fatty liver index is independently
associated with deterioration of renal function during a 10-year period in healthy
subjects. Sci Rep. 2021;11.
29
日本糖尿病学会編. 糖尿病診療ガイドライン 2019. 南江堂. 東京. 2019.
30
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of
92
nonalcoholic fatty liver disease: practice guidance from the American Association for
the Study of Liver Diseases. Hepatology 2018;67:328–57.
31
Marchesini G, Day CP, Dufour JF, et al. EASL-EASD-EASO Clinical Practice
Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;
64: 1388–402.
32
Hozawa S, Maeda S, Kikuchi A, et al. Exploratory research on asthma exacerbation
risk factors using the Japanese claims database and machine learning: a retrospective
cohort study. J Asthma 2021; 59:1328-37.
33
Tuccori M, Filion KB, Yin H, et al. Pioglitazone use and risk of bladder cancer:
population based cohort study. BMJ 2016; 352: i1541.
34
Lincoff AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk of cardiovascular
events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.
JAMA 2007; 298: 1180-8.
35
Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in
type 2 diabetes: a meta-analysis. CMAJ 2009; 180: 32–9.
36
Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of
macrovascular events in patients with type 2 diabetes in the PROactive Study
(PROspective pioglitAzone Clinical Trial in macroVascular Events): A randomised
controlled trial. Lancet 2005; 366: 1279–89.
37
Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with
nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus a randomized
trial. Ann Intern Med 2016; 165: 305–15.
38
Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for
nonalcoholic steatohepatitis. NEJM 2010; 362: 1675–85.
39
Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in
subjects with nonalcoholic steatohepatitis. NEJM 2006; 355: 2297–307.
40
日本消化器病学会編. NAFLD/NASH 診療ガイドライン.南江堂.東京.
2014.
93
41
Komiya C, Tsuchiya K, Shiba K, et al. Ipragliflozin improves hepatic steatosis in
obese mice and liver dysfunction in type 2 diabetic patients irrespective of body
weight reduction. PLoS One 11; 2016: e0151511.
42
Ito D, Shimizu S, Inoue K, et al. Comparison of ipragliflozin and pioglitazone effects
on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24week, open-label, active-controlled trial. Diabetes Care 2017; 40: 1364–72.
43
Seko Y, Nishikawa T, Umemura A, et al. Efficacy and safety of canagliflozin in type 2
diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as
stage 1–3 fibrosis. Diabetes Metab Syndr Obes 2018: 11: 835–43.
44
Akuta N, Watanabe C, Kawamura Y, et al. Effects of a sodium-glucose cotransporter 2
inhibitor in nonalcoholic fatty liver disease complicated by diabetes mellitus:
preliminary prospective study based on serial liver biopsies. Hepatol Commun 2017;
1: 46–52.
45
Yagi N, Komiya I, Arai K, et al. Current status of oral antidiabetic agent prescribing
patterns based on the body mass index for Japanese type 2 diabetes mellitus patients
and yearly changes in diabetologists’ prescribing patterns from 2002 to 2019
(JDDM61). J Diabetes Investig, 2021. doi: 10.1111/jdi.13621.
46
Cusi K, Sanyal AJ, Zhang S, et al. Non-alcoholic fatty liver disease (NAFLD)
prevalence and its metabolic associations in patients with type 1 diabetes and type 2
diabetes. Diabetes Obes Metab 2017; 19: 1630–4
47
Fan H, Pan Q, Xu Y, et al. Exenatide improves type 2 diabetes concomitant with nonalcoholic fatty liver disease. Arq Bras Endocrinol Metabo 2013; 57: 702-8.
48
Shao N, Kuang HY, Hao M, et al. Benefits of exenatide on obesity and non-alcoholic
fatty liver disease with elevated liver enzymes in patients with type 2 diabetes.
Diabetes Metab Res Rev 2014; 30: 521-9.
49
Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients
with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised,
placebo-controlled phase 2 study. Lancet 2016; 387 679-90.
50
Dave CV, Schneeweiss S, Wexler DJ, et al. Trends in Clinical Characteristics and
94
Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 20132018. Diabetes Care 2020; 43: 921-4.
51
Cui J, Philo L, Nguyen P, et al. Sitagliptin vs. placebo for non-alcoholic fatty liver
disease: A randomized controlled trial. J Hepatol 2016; 65: 369-76.
52
Joy TR, McKenzie CA, Tirona RG, et al. Sitagliptin in patients with non-alcoholic
steatohepatitis: A randomized placebo-controlled trial. World J Gastroenterol 2017; 23:
141-50.
53
Carbone LJ, Angus PW, Yeomans ND. Incretin-based therapies for the treatment of
non-alcoholic fatty liver disease: A systemic review and meta-analysis. J gastroenterol
Hepatol 2016; 31: 23-31.
54
Enjoji M, Kotoh K, Kato M, et al. Therapeutic effect of ARBs on insulin resistance
and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study. Int J
Mol Med 2008; 22: 521–7.
55
Georgescu EF, Ionescu R, Niculescu M, et al. Angiotensin-receptor blockers as
therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis.
World Journal of Gastroenterology 2009; 15: 942–54.
56
Yokohama S, Tokusashi Y, Nakamura K, et al. Inhibitory effect of angiotensin II
receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis.
World J Gastroenterol 2006; 12: 322-6.
57
Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II
receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004; 40:
1222–5.
58
Goh GB, Pagadala MR, Dasarathy J, et al. Renin-angiotensin system and fibrosis in
non-alcoholic fatty liver disease Liver Int 2014;35:979-85.
59
日本高血圧学会高血圧治療ガイドライン作成委員会編. 高血圧治療ガイドライ
ン 2014. ライフサイエンス出版. 東京. 2014.
60
Kohro T, Yamazaki T, Sato H, et al. The impact of a change in hypertension
management guidelines on diuretic use in Japan: trends in antihypertensive drug
95
prescriptions from 2005 to 2011. Hypertens Res 2013; 36: 559–63.
61
Kinoshita M, Yokote K, Arai H, et al. Japan Atherosclerosis Society (JAS) Guidelines
for Prevention of Atherosclerotic Cardiovascular Diseases 2017. J Atheroscler Thromb
2018;25:846-984.
62
Fleischman MW, Budoff M, Zeb I, et al. NAFLD prevalence differs among hispanic
subgroups: the Multi-ethnic Study of Atherosclerosis. World J Gastroenterol 2014; 20:
4987–93.
63
Bedogni G, Bellentani S, Miglioli L, et al. The Fatty Liver Index: a simple and
accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol
2006;6:33.
64
Ishibashi S, Yamashita S, Arai H, et al. Effects of K-877, a novel selective PPARα
modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, activeand placebo controlled. Pjase 2 trial. Atherosclerosis 2016;249:36-43.
65
Nakajima A, Eguchi Y, Yoneda M, et al. Randomised clinical trial: Pemafibrate, a
novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα),
versus placebo in patients with non-alcoholic fatty liver disease. Aliment Pharmacol
Ther 2021;54:1263-77.
66
Sanyal AJ, Chalasani Nm Kowdeley KV, et al. Pioglitazone, vitamin E, or placebo for
nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-85.
67
Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with
NAFLD and elevated liver enzymes. Hepatology. 2006;44:865-73.
68
Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality
and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol.
2017;67:1265-73.
69
Bedogni G, Bellentani S, Miglioli L, et al. The fatty liver index: A simple and accurate
predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:17.
70
Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index
96
to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology.
2006;43:1317-25.
71
Ishikuro M, Noda A, Murakami K, et al. Families’ Health after the Great East Japan
Earthquake: Findings from the Tohoku Medical Megabank Project Birth and ThreeGeneration Cohort Study. Tohoku J Exp Med. 2022;256:93-101.
72
Kuriyama S, Metoki H, Kikuya M, et al. Cohort Profile: Tohoku Medical Megabank
Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study):
Rationale, progress and perspective. Int J Epidemiol. 2020;49:18-19M.
73
Ishikuro M, Obara T, Osanai T, et al. Strategic methods for recruiting grandparents:
The Tohoku medical megabank birth and three-generation cohort study. Tohoku J Exp
Med. 2018;246:97-105.
74
Kuriyama S, Yaegashi N, Nagami F, et al. The Tohoku Medical Megabank Project:
Design and mission. J Epidemiol. 2016;26:493-511.
75
Matsuo S, Imai E, Horio M, et al. Revised Equations for Estimated GFR From Serum
Creatinine in Japan. Am J Kidney Dis. 2009;53:982-92.
76
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;7:1104-12.
77
Tamaki N, Kurosaki M, Takahashi Y, et al. Liver fibrosis and fatty liver as independent
risk factors for cardiovascular disease. J Gastroenterol Hepatol. 2021;36:2960-6.
78
Hagström H, Nasr P, Ekstedt M, et al. Cardiovascular risk factors in non-alcoholic
fatty liver disease. Liver Int. 2019;39:197-204.
79
Huh JH, Kim JY, Choi E, et al. The fatty liver index as a predictor of incident chronic
kidney disease in a 10-year prospective cohort study. PLoS ONE. 2017;12.
80
Targher G, Bertolini L, Rodella S, et al. Relationship between kidney function and
liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol.
2010;5:2166-71.
81
Mantovani A, Csermely A, Petracca G,97et al. Non-alcoholic fatty liver disease and risk
of fatal and non-fatal cardiovascular events: an updated systematic review and metaanalysis. Lancet Gastroenterol Hepatol. 2021;6:903-13.
82
Santos RD, Valenti L, Romeo S. Does nonalcoholic fatty liver disease cause
cardiovascular disease? Current knowledge and gaps. Atherosclerosis. 2019;282:11020.
83
Shao Pin Tang A, En Chan K, et al. NAFLD Increases Risk of Carotid Atherosclerosis
and Ischemic Stroke. An Updated Meta-Analysis with 135,602 Individuals. Clin Mol
Hepatol 2022.
84
Wang C, Cai Z, Deng X, et al. Association of hepatic steatosis index and fatty liver
index with carotid atherosclerosis in type 2 diabetes. Int J Med Sci. 2021;18:3280-9.
85
Treeprasertsuk S, Björnsson E, Enders F, et al. NAFLD fibrosis score: a prognostic
predictor for mortality and liver complications among NAFLD patients. World J
Gastroenterol. 2013;19:1219-29.
86
Chen Y, Xu M, Wang T, et al. Advanced fibrosis associates with atherosclerosis in
subjects with nonalcoholic fatty liver disease. Atherosclerosis. 2015;241:145-50.
87
Gentili A, Daviddi G, de Vuono S, et al. Non-alcoholic fatty liver disease fibrosis
score and preclinical vascular damage in morbidly obese patients. Dig Liver Dis.
2016;48:904-8.
88
Sinn DH, Cho SJ, Gu S, et al. Persistent Nonalcoholic Fatty Liver Disease Increases
Risk for Carotid Atherosclerosis. Gastroenterol. 2016;151:481-8.e1
89
Sun K, Lin D, Li F, et al. Fatty liver index, albuminuria and the association with
chronic kidney disease: A population-based study in China. BMJ Open. 2018;8.
90
Crasto C, Semba RD, Sun K, et al. Serum fibroblast growth factor 21 is associated
with renal function and chronic kidney disease in community-dwelling adults. J Am
Geriat Soc. 2012;60:792-3.
91
Dogru T, Genc H, Tapan S, et al. Plasma fetuin-A is associated with endothelial
dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver
disease. Clin Endocrinol. 2013;78:712-7
98
92
Ix JH, Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver
disease: The roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol.
2010;21:406-12.
93
Yilmaz Y, Eren F, Yonal O, et al. Increased serum FGF21 levels in patients with
nonalcoholic fatty liver disease. Eur J Clin Investig. 2010;40:887-92.
94
Cheung A, Ahmed A. Nonalcoholic fatty liver disease and chronic kidney disease: A
review of links and risks. Clin Exp Gastroenterol. 2021;14:457-65.
95
Kim DH, Park JS, Choi HI, et al. The critical role of FXR is associated with the
regulation of autophagy and apoptosis in the progression of AKI to CKD. Cell Death
Dis. 2021;12.
96
Menon V, Gul A, Sarnak MJ. Cardiovascular risk factors in chronic kidney disease.
Kidney Int. 2005:68:1413-8.
97
日本高血圧学会高血圧治療ガイドライン作成委員会編. 高血圧治療ガイドライ
ン 2019. ライフサイエンス出版. 東京. 2019.
98
Suzuki Y, Kaneko H, Okada A, et al. Kidney outcomes in patients with diabetes
mellitus did not differ between individual sodium-glucose cotransporter-2 inhibitors.
Kidney Int 2022; 102: 1147-53.
99
Shao SC, Chang KC, Lin SJ, et al. Differences in outcomes of hospitalizations for
heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic
cardiovascular disease. 2021; 20: 213.
100
Lin YH, Huang YY, Hsieh SH, et al. Renal and Glucose-Lowering Effects of
Empagliflozin and Dapagliflozin in Different Chronic Kidney Disease Stages. Front
Endocrinol (Lausanne) 2019; 10: 820.
101
Tager T, Frankenstein L, Atar D, et al. Influence of receptor selectivity on benefits
from SGLT2 inhibitors in patients with heart failure: a systematic review and head-tohead comparative efficacy network meta-analysis. Clin Res Cardiol 2022; 111: 42839.
102
Ishida T, Oh A, Hiroi S, et al. Current prescription status of antihypertensive drugs in
99
Japanese patients with hypertension: Analysis by type of comorbidities. Clin Exp
Hypertens. 2019;41:203-210.
103
Jimba S, Nakagami T, Takahashi M, et al. Prevalence of non-alcoholic fatty liver
disease and its association with impaired glucose metabolism in Japanese adults.
Diabet Med 2005; 22: 1141–5.
104
Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease burden in
China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for
the period 2016–2030. J Hepatol 2018; 69: 896–904.
105
Luise C, Sugiyama N, Morishima T, et al. Validity of claims-based algorithms for
selected cancers in Japan: Results from the VALIDATE-J study. Pharmacoepidemiol
Drug Saf 2021; 30: 1153-61.
100
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