Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management

被引:174
作者
Marjot, Thomas [1 ,2 ]
Moolla, Ahmad [2 ]
Cobbold, Jeremy F. [1 ]
Hodson, Leanne [2 ]
Tomlinson, Jeremy W. [2 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Translat Gastroenterol Unit, Oxford, England
[2] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, NIHR Oxford Biomed Res Ctr, Oxford, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
NAFLD; NASH; liver; diabetes; obesity; DE-NOVO LIPOGENESIS; TISSUE INSULIN-RESISTANCE; TYPE-2; DIABETES-MELLITUS; POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE SLEEP-APNEA; POLYCYSTIC-OVARY-SYNDROME; NECROSIS-FACTOR-ALPHA; INTESTINAL BACTERIAL OVERGROWTH; SERUM ALANINE AMINOTRANSFERASE; HORMONE REPLACEMENT THERAPY;
D O I
10.1210/endrev/bnz009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disease, extending from simple steatosis to inflammation and fibrosis with a significant risk for the development of cirrhosis. It is highly prevalent and is associated with significant adverse outcomes both through liver-specific morbidity and mortality but, perhaps more important, through adverse cardiovascular and metabolic outcomes. It is closely associated with type 2 diabetes and obesity, and both of these conditions drive progressive disease toward the more advanced stages. The mechanisms that govern hepatic lipid accumulation and the predisposition to inflammation and fibrosis are still not fully understood but reflect a complex interplay between metabolic target tissues including adipose and skeletal muscle, and immune and inflammatory cells. The ability to make an accurate assessment of disease stage (that relates to clinical outcome) can also be challenging. While liver biopsy is still regarded as the gold-standard investigative tool, there is an extensive literature on the search for novel noninvasive biomarkers and imaging modalities that aim to accurately reflect the stage of underlying disease. Finally, although no therapies are currently licensed for the treatment of NAFLD, there are interventions that appear to have proven efficacy in randomized controlled trials as well as an extensive emerging therapeutic landscape of new agents that target many of the fundamental pathophysiological processes that drive NAFLD. It is highly likely that over the next few years, new treatments with a specific license for the treatment of NAFLD will become available. [GRAPHICS] .
引用
收藏
页码:66 / 117
页数:52
相关论文
共 534 条
[1]   Increased Fructose Consumption Is Associated with Fibrosis Severity in Patients with Nonalcoholic Fatty Liver Disease [J].
Abdelmalek, Manal F. ;
Suzuki, Ayako ;
Guy, Cynthia ;
Unalp-Arida, Aynur ;
Colvin, Ryan ;
Johnson, Richard J. ;
Diehl, Anna Mae .
HEPATOLOGY, 2010, 51 (06) :1961-1971
[2]  
Abel T, 2009, MED SCI MONITOR, V15, pMS6
[3]   Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease; the importance of an elevated mean platelet volume [J].
Abeles, Robin D. ;
Mullish, Benjamin H. ;
Forlano, Roberta ;
Kimhofer, Torben ;
Adler, Maciej ;
Tzallas, Alexandros ;
Giannakeas, Nikolaos ;
Yee, Michael ;
Mayet, Jamil ;
Goldin, Robert D. ;
Thursz, Mark R. ;
Manousou, Pinelopi .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2019, 49 (08) :1077-1085
[4]   Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8 [J].
Abu Shanab, Ahmed ;
Scully, Paul ;
Crosbie, Orla ;
Buckley, Martin ;
O'Mahony, Liam ;
Shanahan, Fergus ;
Gazareen, Sanaa ;
Murphy, Eileen ;
Quigley, Eamonn M. M. .
DIGESTIVE DISEASES AND SCIENCES, 2011, 56 (05) :1524-1534
[5]   A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease [J].
Abul-Husn, N. S. ;
Cheng, X. ;
Li, A. H. ;
Xin, Y. ;
Schurmann, C. ;
Stevis, P. ;
Liu, Y. ;
Kozlitina, J. ;
Stender, S. ;
Wood, G. C. ;
Stepanchick, A. N. ;
Still, M. D. ;
McCarthy, S. ;
O'Dushlaine, C. ;
Packer, J. S. ;
Balasubramanian, S. ;
Gosalia, N. ;
Esopi, D. ;
Kim, S. Y. ;
Mukherjee, S. ;
Lopez, A. E. ;
Fuller, E. D. ;
Penn, J. ;
Chu, X. ;
Luo, J. Z. ;
Mirshahi, U. L. ;
Carey, D. J. ;
Still, C. D. ;
Feldman, M. D. ;
Small, A. ;
Damrauer, S. M. ;
Rader, D. J. ;
Zambrowicz, B. ;
Olson, W. ;
Murphy, A. J. ;
Borecki, I. B. ;
Shuldiner, A. R. ;
Reid, J. G. ;
Overton, J. D. ;
Yancopoulos, G. D. ;
Hobbs, H. H. ;
Cohen, J. C. ;
Gottesman, O. ;
Teslovich, T. M. ;
Baras, A. ;
Mirshahi, T. ;
Gromada, J. ;
Dewey, F. E. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (12) :1096-1106
[6]   High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase [J].
Adachi, Masayuki ;
Brenner, David A. .
HEPATOLOGY, 2008, 47 (02) :677-685
[7]   Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases [J].
Adams, Leon A. ;
Anstee, Quentin M. ;
Tilg, Herbert ;
Targher, Giovanni .
GUT, 2017, 66 (06) :1138-1153
[8]   Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis [J].
Aithal, Guruprasad P. ;
Thomas, James A. ;
Kaye, Philip V. ;
Lawson, Adam ;
Ryder, Stephen D. ;
Spendlove, Ian ;
Austin, Andrew S. ;
Freeman, Jan G. ;
Morgan, Linda ;
Weeber, Jonathan .
GASTROENTEROLOGY, 2008, 135 (04) :1176-1184
[9]   Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease [J].
Ajmera, Veeral ;
Park, Charlie C. ;
Caussy, Cyrielle ;
Singh, Seema ;
Hernandez, Carolyn ;
Bettencourt, Ricki ;
Hooker, Jonathan ;
Sy, Ethan ;
Behling, Cynthia ;
Xu, Ronghui ;
Middleton, Michael S. ;
Valasek, Mark A. ;
Faulkner, Claire ;
Rizo, Emily ;
Richards, Lisa ;
Sirlin, Claude B. ;
Loomba, Rohit .
GASTROENTEROLOGY, 2018, 155 (02) :307-+
[10]   Impact of sodium glucose cotransporter 2 inhibitor on histological features and glucose metabolism of non-alcoholic fatty liver disease complicated by diabetes mellitus [J].
Akuta, Norio ;
Kawamura, Yusuke ;
Watanabe, Chizuru ;
Nishimura, Akihiro ;
Okubo, Minoru ;
Mori, Yasumichi ;
Fujiyama, Shunichiro ;
Sezaki, Hitomi ;
Hosaka, Tetsuya ;
Kobayashi, Masahiro ;
Kobayashi, Mariko ;
Saitoh, Satoshi ;
Suzuki, Fumitaka ;
Suzuki, Yoshiyuki ;
Arase, Yasuji ;
Ikeda, Kenji ;
Kumada, Hiromitsu .
HEPATOLOGY RESEARCH, 2019, 49 (05) :531-539