The additive effect of genetic and metabolic factors in the pathogenesis of nonalcoholic fatty liver disease

被引：5

作者：

Seko, Yuya ^{[1
]}

Yamaguchi, Kanji ^{[1
]}

Yano, Kota ^{[1
]}

Takahashi, Yusuke ^{[1
]}

Takeuchi, Kento ^{[1
]}

Kataoka, Seita ^{[1
]}

Moriguchi, Michihisa ^{[1
]}

Itoh, Yoshito ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, Kamigyou Ku, Kawaramachi Hirokji, Kyoto 6028566, Japan

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

PNPLA3; RISK; FIBROSIS; VARIANT; STEATOHEPATITIS; CIRRHOSIS;

D O I：

10.1038/s41598-022-22729-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Both genetic and metabolic factors influence the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to evaluate the impact of these factors at each stage of disease. We analysed the impact of obesity, diabetes mellitus and genetic risk factors (alleles of PNPLA3 or HSD17B13) on nonalcoholic steatohepatitis (NASH), significant fibrosis (stage >= 2) and advanced fibrosis (stage >= 3) in 346 patients. Genetic high risk was defined as having at least 2 risk alleles. The median age was 59 years, median body mass index was 27.1 kg/m(2), and 46.8% had diabetes mellitus. Obesity was a risk factor for NASH, significant fibrosis, and advanced fibrosis. Diabetes mellitus increased the risk of NASH. Genetic risk increased the risk of significant and advanced fibrosis. Odds ratios for NASH, significant fibrosis and advanced fibrosis increased with the number of genetic and metabolic risk factors. The patients with both metabolic and genetic risks had an odds ratio of 12.30 for NASH, 5.50 for significant fibrosis, and 6.25 for advanced fibrosis. Factors strongly impact on the pathology of NAFLD differed according to the fibrosis stages. Synergistic effects were observed between genetic and metabolic factors at all stages.

引用

页数：8

共 35 条

[11] Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study [J].

Fujii, Hideki ;

Iwaki, Michihiro ;

Hayashi, Hideki ;

Toyoda, Hidenori ;

Oeda, Satoshi ;

Hyogo, Hideyuki ;

Kawanaka, Miwa ;

Morishita, Asahiro ;

Munekage, Kensuke ;

Kawata, Kazuhito ;

Yamamura, Sakura ;

Sawada, Koji ;

Maeshiro, Tatsuji ;

Tobita, Hiroshi ;

Yoshida, Yuichi ;

Naito, Masafumi ;

Araki, Asuka ;

Arakaki, Shingo ;

Kawaguchi, Takumi ;

Noritake, Hidenao ;

Ono, Masafumi ;

Masaki, Tsutomu ;

Yasuda, Satoshi ;

Tomita, Eiichi ;

Yoneda, Masato ;

Kawada, Norifumi ;

Tokushige, Akihiro ;

Kamada, Yoshihiro ;

Takahashi, Hirokazu ;

Ueda, Shinichiro ;

Aishima, Shinichi ;

Sumida, Yoshio ;

Nakajima, Atsushi ;

Okanoue, Takeshi .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2023, 21 (02) :370-379

[12] Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population [J].

Gellert-Kristensen, Helene ;

Richardson, Tom G. ;

Davey Smith, George ;

Nordestgaard, Borge G. ;

Tybjaerg-Hansen, Anne ;

Stender, Stefan .

HEPATOLOGY, 2020, 72 (03) :845-856

[13] Metabolic and Genetic Risk Factors Are the Strongest Predictors of Severity of Alcohol-Related Liver Fibrosis [J].

Israelsen, Mads ;

Juel, Helene Baek ;

Detlefsen, Sonke ;

Madsen, Bjorn Staehr ;

Rasmussen, Ditlev Nytoft ;

Larsen, Trine R. ;

Kjaergaard, Maria ;

Jensen, Mary Jo Fernandes ;

Stender, Stefan ;

Hansen, Torben ;

Krag, Aleksander ;

Thiele, Maja .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2022, 20 (08) :1784-+

[14] Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease [J].

Kanwal, Fasiha ;

Kramer, Jennifer R. ;

Li, Liang ;

Dai, Jianliang ;

Natarajan, Yamini ;

Yu, Xian ;

Asch, Steven M. ;

El-Serag, Hashem B. .

HEPATOLOGY, 2020, 71 (03) :808-819

[15] Design and validation of a histological scoring system for nonalcoholic fatty liver disease [J].

Kleiner, DE ;

Brunt, EM ;

Van Natta, M ;

Behling, C ;

Contos, MJ ;

Cummings, OW ;

Ferrell, LD ;

Liu, YC ;

Torbenson, MS ;

Unalp-Arida, A ;

Yeh, M ;

McCullough, AJ ;

Sanyal, AJ .

HEPATOLOGY, 2005, 41 (06) :1313-1321

[16] Adiponutrin Functions as a Nutritionally Regulated Lysophosphatidic Acid Acyltransferase [J].

Kumari, Manju ;

Schoiswohl, Gabriele ;

Chitraju, Chandramohan ;

Paar, Margret ;

Cornaciu, Irina ;

Rangrez, Ashraf Y. ;

Wongsiriroj, Nuttaporn ;

Nagy, Harald M. ;

Ivanova, Pavlina T. ;

Scott, Sarah A. ;

Knittelfelder, Oskar ;

Rechberger, Gerald N. ;

Birner-Gruenberger, Ruth ;

Eder, Sandra ;

Brown, H. Alex ;

Haemmerle, Guenter ;

Oberer, Monika ;

Lass, Achim ;

Kershaw, Erin E. ;

Zimmermann, Robert ;

Zechner, Rudolf .

CELL METABOLISM, 2012, 15 (05) :691-702

[17] Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma [J].

Liu, Y. -L. ;

Patman, G. L. ;

Leathart, J. B. S. ;

Piguet, A. -C. ;

Burt, A. D. ;

Dufour, J. -F. ;

Day, C. P. ;

Daly, A. K. ;

Reeves, H. L. ;

Anstee, Q. M. .

JOURNAL OF HEPATOLOGY, 2014, 61 (01) :75-81

[18] 17-Beta Hydroxysteroid Dehydrogenase 13 Is a Hepatic Retinol Dehydrogenase Associated With Histological Features of Nonalcoholic Fatty Liver Disease [J].

Ma, Yanling ;

Belyaeva, Olga V. ;

Brown, Philip M. ;

Fujita, Koji ;

Valles, Katherine ;

Karki, Suman ;

de Boer, Ynto S. ;

Koh, Christopher ;

Chen, Yanhua ;

Du, Xiaomeng ;

Handelman, Samuel K. ;

Chen, Vincent ;

Speliotes, Elizabeth K. ;

Nestlerode, Cara ;

Thomas, Emmanuel ;

Kleiner, David E. ;

Zmuda, Joseph M. ;

Sanyal, Arun J. ;

Kedishvili, Natalia Y. ;

Liang, T. Jake ;

Rotman, Yaron .

HEPATOLOGY, 2019, 69 (04) :1504-1519

[19] Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients [J].

Nakahara, Takashi ;

Hyogo, Hideyuki ;

Yoneda, Masato ;

Sumida, Yoshio ;

Eguchi, Yuichiro ;

Fujii, Hideki ;

Ono, Masafumi ;

Kawaguchi, Takumi ;

Imajo, Kento ;

Aikata, Hiroshi ;

Tanaka, Saiyu ;

Kanemasa, Kazuyuki ;

Fujimoto, Kazuma ;

Anzai, Keizo ;

Saibara, Toshiji ;

Sata, Michio ;

Nakajima, Atushi ;

Itoh, Yoshito ;

Chayama, Kazuaki ;

Okanoue, Takeshi .

JOURNAL OF GASTROENTEROLOGY, 2014, 49 (11) :1477-1484

[20] Clinical, Laboratory and Histological Associations in Adults with Nonalcoholic Fatty Liver Disease [J].

Nettschwander-Tetri, Brent A. ;

Clark, Jeanne M. ;

Bass, Nathan M. ;

Van Natta, Mark L. ;

Unalp-Arida, Aynur ;

Tonascia, James ;

Zein, Claudia O. ;

Brunt, Elizabeth M. ;

Kleiner, David E. ;

McCullough, Arthur J. ;

Sanyal, Arun J. ;

Diehl, Anna Mae ;

Lavine, Joel E. ;

Chalasani, Naga ;

Kowdley, Kris V. .

HEPATOLOGY, 2010, 52 (03) :913-924

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