Hepatocyte and immune cell crosstalk in non-alcoholic fatty liver disease

ABSTRACT

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease in the world. It can evolve into nonalcoholic steatohepatitis (NASH) where inflammation and hepatocyte ballooning are key participants in the determination of this steatotic state.

Areas covered: To provide a systematic overview and current understanding of the role of inflammation in NAFLD and its progression to NASH, the function of the cells involved, and the activation pathways of the innate immunity and cell death; resulting in inflammation and chronic liver disease. A PubMed search was made with relevant articles together with relevant references were included for the writing of this review.

Expert opinion: Innate and adaptive immunity are the key players in the NAFLD progression; some of the markers presented during NAFLD are also known to be immunity biomarkers. All cells involved in NAFLD and NASH are known to have immunoregulatory properties and their imbalance will completely change the cytokine profile and form a pro-inflammatory microenvironment. It is necessary to fully answer the question of what initiators and metabolic imbalances are particularly important, considering sterile inflammation as the architect of the disease. Due to the shortage of elucidation of NASH progression, we discuss in this review, how inflammation is a key part of this development and we presume the targets should lead to inflammation and oxidative stress treatment.

KEYWORDS:

• Fat
• immune system
• liver
• inflammation
• nonalcoholic fatty liver disease
• obesity
• steatosis
• sterile inflammation

Article highlights

• NAFLD and its subsequent state, NASH, are the number one cause of chronic liver disease and liver transplantation in the world.

• Inflammation is a key role player in the chronic evolution of this pathology.

• Hepatocyte ballooning followed by sterile inflammation are the origin of the disease.

• In late stages hepatocellular death takes place following several programmed cell death mechanisms.

• New drugs and medication should target the inflammatory pathways to stop the fibrosis progression.

Declaration of interest

Both A Carranza and M Kralickova receive funding from the Ministry of Education, Youth and Sports of the Czech Republic/European Regional Development Fund. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The study was supported by the Ministry of Education, Youth and Sports of the Czech Republic, financed from The European Regional Development Fund, project number CZ.02.1.01/0.0/0.0/16_019/0000787 ‘Fighting Infectious Diseases’.