TY - JOUR
T1 - Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis
T2 - Exploiting similarities and differences in pathogenesis
AU - Greuter, Thomas
AU - Malhi, Harmeet
AU - Gores, Gregory J.
AU - Shah, Vijay H.
N1 - Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/9/7
Y1 - 2017/9/7
N2 - Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are among the most frequent causes of chronic liver disease in the United States. Although the two entities are triggered by different etiologies — chronic alcohol consumption (ASH) and obesity-associated lipotoxicity (NASH) — they share overlapping histological and clinical features owing to common pathogenic mechanisms. These pathogenic processes include altered hepatocyte lipid metabolism, organelle dysfunction (i.e., ER stress), hepatocyte apoptosis, innate immune system activation, and hepatic stellate cell activation. Nonetheless, there are several disease-specific molecular signaling pathways, such as differential pathway activation downstream of TLR4 (MyD88-dependence in NASH versus MyD88-independence in ASH), inflammasome activation and IL-1β signaling in ASH, insulin resistance and lipotoxicity in NASH, and dysregulation of different microRNAs, which clearly highlight that ASH and NASH are two distinct biological entities. Both pathogenic similarities and differences have therapeutic implications. In this Review, we discuss these pathogenic mechanisms and their therapeutic implications for each disease, focusing on both shared and distinct targets.
AB - Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are among the most frequent causes of chronic liver disease in the United States. Although the two entities are triggered by different etiologies — chronic alcohol consumption (ASH) and obesity-associated lipotoxicity (NASH) — they share overlapping histological and clinical features owing to common pathogenic mechanisms. These pathogenic processes include altered hepatocyte lipid metabolism, organelle dysfunction (i.e., ER stress), hepatocyte apoptosis, innate immune system activation, and hepatic stellate cell activation. Nonetheless, there are several disease-specific molecular signaling pathways, such as differential pathway activation downstream of TLR4 (MyD88-dependence in NASH versus MyD88-independence in ASH), inflammasome activation and IL-1β signaling in ASH, insulin resistance and lipotoxicity in NASH, and dysregulation of different microRNAs, which clearly highlight that ASH and NASH are two distinct biological entities. Both pathogenic similarities and differences have therapeutic implications. In this Review, we discuss these pathogenic mechanisms and their therapeutic implications for each disease, focusing on both shared and distinct targets.
UR - http://www.scopus.com/inward/record.url?scp=85038960754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038960754&partnerID=8YFLogxK
U2 - 10.1172/JCI.INSIGHT.95354
DO - 10.1172/JCI.INSIGHT.95354
M3 - Review article
C2 - 28878132
AN - SCOPUS:85038960754
SN - 2379-3708
VL - 2
JO - JCI Insight
JF - JCI Insight
IS - 17
M1 - e95354
ER -