Spotlight on liver macrophages for halting injury and progression in nonalcoholic fatty liver disease

ABSTRACT

Introduction

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and is rapidly emerging as the leading cause of liver-related morbidity and mortality. Macrophages play an essential role in the development and progression of NAFLD.

Areas covered

In this review, we provide an update on recent studies of drugs, which directly or indirectly affect macrophages in NAFLD, and discuss the implication of macrophage biomarkers to monitor the disease stage and progression/regression.

Expert opinion

There is an unmet need for a better understanding of disease pathogenesis from hepatic fat accumulation to disease progression with inflammation and fibrosis. We expect that future research will uncover additional objects/pathways as treatment targets. We speculate that this will involve better characterization of the gut microbiome, damage-associated molecular patterns (DAMPS) or molecules and pathways involved in the development of DAMPS, and advanced molecular biology studies including single-cell sequencing of macrophage subpopulations. In addition, we speculate that studies focusing on pharmaceuticals that improve insulin resistance, diminish the metabolic syndrome, and reduce fibrosis will prevail.

KEYWORDS:

• Macrophages
• metabolic syndrome
• nonalcoholic fatty liver disease (NAFLD)
• nonalcoholic steatohepatitis (NASH)
• obesity
• soluble CD163

Article highlights

• Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease affecting approximately 25% of the world population.

• Macrophages play a key role in NAFLD disease development and progression.

• Macrophages may be activated through different pathways of interorgan cross-talk, e.g. the gut microbiota and pathogen-associated molecular patterns, adipose tissue with free fatty acids and adipocytokines, and damage-associated molecular patterns from hepatocytes.

• Targeting macrophages directly or indirectly may ameliorate liver inflammation and fibrosis in NAFLD patients.

• Macrophage activation markers may be used as surrogate markers for disease severity and treatment response or even prognosis.

This box summarizes key points contained in the article.

Declaration of interest

H Grønbæk has received research grants from AbbVie, Intercept, ARLA Food for Health, ADS AIPHIA Development Services AG and consulting fees from Ipsen, NOVO, and Pfizer. He has served as a lecturer for AstraZeneca and EISAI, and on the data Monitoring Committee for IQVIA.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.