Tarantino G, Citro V. Liver-spleen axis: Deciphering a crucial crosstalk in non-alcoholic fatty liver disease progression and therapeutic implications. World J Gastroenterol 2026; 32(34): 119467 [DOI: 10.3748/wjg.119467]
Corresponding Author of This Article
Giovanni Tarantino, MD, Department of Clinical Medicine and Surgery, Federico II University Medical School, Via Pietro Castellino 128, Naples 80131, Italy. tarantin@unina.it
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Sep 14, 2026; 32(34): 119467 Published online Sep 14, 2026. doi: 10.3748/wjg.119467
Liver-spleen axis: Deciphering a crucial crosstalk in non-alcoholic fatty liver disease progression and therapeutic implications
Giovanni Tarantino, Vincenzo Citro
Giovanni Tarantino, Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples 80131, Italy
Giovanni Tarantino, Department of Internal Medicine, Medical Faculty, Ataturk University, Erzurum 25240, Türkiye
Vincenzo Citro, Department of General Medicine, Umberto I Hospital, Nocera Inferiore 84014, Italy
Author contributions: Tarantino G was responsible for the conceptualization, methodology, software, writing (original draft, review, and editing), visualization, and validation; Citro V was responsible for writing (review and editing), methodology, and data curation.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Corresponding author: Giovanni Tarantino, MD, Department of Clinical Medicine and Surgery, Federico II University Medical School, Via Pietro Castellino 128, Naples 80131, Italy. tarantin@unina.it
Received: January 29, 2026 Revised: March 5, 2026 Accepted: April 20, 2026 Published online: September 14, 2026 Processing time: 203 Days and 9.4 Hours
Core Tip
Core Tip: Traditional models of non-alcoholic fatty liver disease focus on the “liver-adipose-gut axis,” but emerging evidence establishes the “liver-spleen axis” as a critical immunometabolic rheostat. The spleen acts as an active “priming station” where metabolic stress triggers immune reprogramming. Splenic monocytes and pro-inflammatory cytokines are deployed via the portal circulation to the liver, accelerating steatohepatitis and fibrosis. Clinically, spleen longitudinal diameter measured by ultrasound and splenic metabolic activity assessed via positron emission tomography/computed tomography serve as high-reliability, non-invasive biomarkers of disease severity. Targeting this axis offers a novel frontier for precision diagnostics and interventions to halt metabolic and systemic inflammatory decay.
