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Mechanisms and disease consequences of nonalcoholic fatty liver disease

期刊

CELL
卷 184, 期 10, 页码 2537-2564

出版社

CELL PRESS
DOI: 10.1016/j.cell.2021.04.015

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资金

  1. Department of Health and Human Services (NIH/NIDDK/NHLBI/NIEHS/NCATS) [R01 DK56621, DK128289, R01 DK113984, R01 DK114793, R01 DK116774, R01 DK119968, RC2 DK120534, P30 DK045735, UL1 TR001442, U01 DK061734, R01 DK106419, R01 DK121378, R01 DK124318, P30 DK120515, P01 HL147835, P42 ES01033]

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NAFLD and NASH are leading chronic liver diseases worldwide, causing progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. These diseases are associated with hepatic glucose and lipid metabolism, and are influenced by genetic, epigenetic, and environmental factors.
Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. Here we provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAFLD, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH.

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