The spleen in liver cirrhosis: revisiting an old enemy with novel targets

Abstract

The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.

The Spleen Promotes the Secretion of CCL2 and Supports an M1 Dominant Phenotype in Hepatic Macrophages During Liver Fibrosis

“…Splenic immune cells, particularly the resident macrophages and mobilizable monocytes within the reservoir in red pulp, are involved in various inflammatory diseases. Previously, the spleen was thought to promote the progression of liver fibrosis through the generation of pro-inflammatory and pro-fibrogenic factors [15]. However, whether and how the spleen can modulate hepatic monocytes/macrophages to affect liver fibrosis remains unclear.…”

“…Given the anatomical proximity between the spleen and liver via the portal vein as well as the frequent involvement of splenic abnormalities in liver diseases, a "liver-spleen axis" has been proposed [15,16]. Clinically, liver cirrhosis is often accompanied by splenomegaly and hypersplenism.…”

IMPORTANCE OF THE LEPTIN/GRELIN RATIO AS A BIOMARKER IN DIETARY INDUCED HYPERLIPIDEMIA IN FEMALE C57Black/6 MICE

“…Анатомическая и функциональная связь этих органов в регуляции метаболических процессов в норме и при патологии общеизвестна. В частности, при фиброзных изменениях в печени (независимо от этиологического фактора) неизбежно происходят дистрофические изменения в тканях селезенки [16,25]. Взаимосвязь между изменениями L/Gh и массой органов и тканей может быть обусловлена участием лептина и грелина в регуляции ангиогенеза и формировании фиброзных изменений, которые наблюдаются при ожирении и метаболическом синдроме.…”

“…На этом фоне системное введение грелина мышам, получающим обогащенный жирами рацион, способствовало увеличению сывороточного VEGF (фактор роста эндотелия) и снижению сывороточных концентраций лептина и NO (окись азота II) [19]. Лептин и грелин, наравне с цитокинами, обладают плейотропной активностью и участвуют в механизмах регуляции воспаления, как одного из компонентов метаболического синдрома [23,25,33]. Корреляционная зависимость L/Gh, показателей абсолютной и относительной массы органов и тканей с рядом достоверно изменяющихся концентраций цитокинов в плазме мышей -достаточно интересная и закономерная находка.…”

Correlation of postoperative splenic volume increase with prognosis of hepatocellular carcinoma after curative hepatectomy

“…Immunologically, they both play important roles in immune homeostasis. 3 Previous studies have shown that splenic volume increased after major hepatectomy. [4][5][6] Cortez-Retamozo and colleagues 7 found that removal of the spleen, before or after tumour origination, significantly reduced the responses of tumour-associated macrophages and neutrophils, and delayed tumour growth, which confirmed the close connection between the spleen and the hepatic tumour.…”