Mikkel Breinholt Kjær

TY - JOUR

T1 - Current perspectives on the pathophysiology of metabolic associated fatty liver disease: are macrophages a viable target for therapy?

AU - Kjær, Mikkel Breinholt

AU - George, Jacob

AU - Kazankov, Konstantin

AU - Grønbæk, Henning

PY - 2021/1

Y1 - 2021/1

N2 - INTRODUCTION: Metabolic associated fatty liver disease (MAFLD) is a new nomenclature for fatty liver replacing non-alcoholic fatty liver disease (NAFLD). MAFLD has emerged as the leading cause of liver-related morbidity and mortality with increasing incidence due to its close association with the global epidemic of obesity and type 2 diabetes mellitus. Macrophages play a key role in MAFLD development and progression of steatohepatitis and fibrosis. Therefore, targeting macrophages may be a new therapeutic approach for MAFLD and MAFLD with steatohepatitis.AREAS COVERED: We provide a comprehensive review of the significant role of macrophages in MAFLD. Further, we evaluate the current status of lifestyle interventions and pharmacological treatments with a focus on effects mediated through direct or indirect targeting of macrophages.EXPERT OPINION: Targeting macrophages holds promise as a treatment option for the management of MAFLD and steatohepatitis. Improved stratification of patients according to MAFLD phenotype would contribute to more adequate design enhancing the yield of clinical trials ultimately leading to personalized medicine for patients with MAFLD. Furthermore, reflecting the multifactorial pathogenesis of MAFLD, combination therapies based on the various pathophysiological driver events including as pertinent to this review, macrophage recruitment, polarization and action, present an intriguing target for future investigation.

AB - INTRODUCTION: Metabolic associated fatty liver disease (MAFLD) is a new nomenclature for fatty liver replacing non-alcoholic fatty liver disease (NAFLD). MAFLD has emerged as the leading cause of liver-related morbidity and mortality with increasing incidence due to its close association with the global epidemic of obesity and type 2 diabetes mellitus. Macrophages play a key role in MAFLD development and progression of steatohepatitis and fibrosis. Therefore, targeting macrophages may be a new therapeutic approach for MAFLD and MAFLD with steatohepatitis.AREAS COVERED: We provide a comprehensive review of the significant role of macrophages in MAFLD. Further, we evaluate the current status of lifestyle interventions and pharmacological treatments with a focus on effects mediated through direct or indirect targeting of macrophages.EXPERT OPINION: Targeting macrophages holds promise as a treatment option for the management of MAFLD and steatohepatitis. Improved stratification of patients according to MAFLD phenotype would contribute to more adequate design enhancing the yield of clinical trials ultimately leading to personalized medicine for patients with MAFLD. Furthermore, reflecting the multifactorial pathogenesis of MAFLD, combination therapies based on the various pathophysiological driver events including as pertinent to this review, macrophage recruitment, polarization and action, present an intriguing target for future investigation.

KW - CD163

KW - NAFLD

KW - NASH

KW - cirrhosis

KW - kupffer cells

KW - macrophages

KW - metabolic associated fatty liver disease

KW - nonalcoholic fatty liver disease

KW - nonalcoholic steatohepatitis

U2 - 10.1080/17474124.2020.1817740

DO - 10.1080/17474124.2020.1817740

M3 - Review

C2 - 32878486

VL - 15

SP - 51

EP - 64

JO - Expert Review of Gastroenterology & Hepatology

JF - Expert Review of Gastroenterology & Hepatology

SN - 1747-4124

IS - 1

ER -