Liver-spleen axis in nonalcoholic fatty liver disease

ABSTRACT

Introduction: NAFLD is often under-diagnosed, even though rates of its co-morbidities such as obesity and type2 diabetes mellitus, prominent statuses of inflammation, are significantly high. The spleen-liver axis is gaining much credit in the last years like other well-known organ axes.

Areas covered: PubMed/MEDLINE was searched for relevant articles related to concomitant occurrence of NAFLD and spleen. Areas covered in this review include: (1) updated findings of spleen dimensions at ultrasonography, (2) discussion of current data on pathophysiological connections between obesity-related NAFLD and increased volume of the spleen, and (3) analysis of current immune-mediated mechanisms characterizing the so.called chronic low-grade inflammation leading to insulin resistance.

Expert opinion: The advances in explaining mechanisms underlying the spleen involvement in immune regulation, coupled with research about the role of spleen in NAFLD, could impact real world outcomes through establishing better tools for a precocious diagnosis. Using both liver and spleen ultrasonography, technique largely dealt with in this review, could expand the possibility to cover an adequate diagnostic path toward NAFLD, reaching a good sensibility and specificity.

KEYWORDS:

• Obesity
• NAFLD
• ultrasound
• spleen longitudinal diameter
• chronic low grade inflammation

Abbreviations

Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), metabolic syndrome (MS), metabolic associated fatty liver disease (MALFD), maximum length (ML), splenic length (SL), spleen longitudinal diameter (SLD), spleen width (SW), thickness (ST), craniocaudal length (CCL), vascular endothelial growth factor (VEGF), spleen-body index (SBI), diet-inducing obesity (DIO), visceral adipose tissue (VAT), regulatory T cells (Tregs), granulocyte and macrophage progenitors (CFU-GM), monosodium-glutamate (MSG), lysosomal acid lipase (LAL), insulin-like growth factor (IGF), metabolic rate of glucose (MRglu), dendritic cells (DCs), chronic renal failure (CRF), polycystic ovary syndrome (PCOS), obstructive sleep apnoea syndrome (OSAS).

Article highlights

• NAFLD is the most frequent chronic liver disease and is on the verge of being the main cause of liver transplantation.

• Increased awareness, particularly in subjects with obesity/metabolic syndrome, is needed to reach a precocious diagnosis of NAFLD.

• Spleen involvement in NAFLD has been reported by several authors.

• Potential pathogenic connections between low-grade chronic inflammation and insulin resistance, mediated by spleen immune system, have been unravelled. Their study help to deepen the understanding of this complex disease that is NAFLD, better defined as MALFD.

• A finding of enlarged spleen, based on ultrasonographic dimensions, could help standardise NAFLD assessment.

Declaration of interest

The authors have no 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