Is HMGB1 a New Indirect Marker for Revealing Fibrosis in Chronic Hepatitis and a New Therapeutic Target in Treatment?

Abstract

In chronic hepatitis B virus (HBV) infection, inflammation-associated cytokines including proinflammatory cytokines are involved in the development and progression of liver fibrosis. The liver is a source of many cytokines that may influence liver function. High-mobility group box 1 (HMGB1) was identified as an inflammatory cytokine. HMGB1 is present in nuclei of all mammalian cells and is released both through active secretion from various cells and by passive release from necrotic cells. Here we explore the relationship between HMGB1 plasma levels and liver fibrosis. HMGB1 serum levels, HBV-DNA, and ALT values were significantly higher in patients with chronic HBV than in controls. In addition, HMGB1 serum levels were significantly higher in patients with low fibrosis (fibrosis score 1-2) compared to those with high fibrosis (fibrosis score 3-4). In the present study, we have shown that HMGB1 is a noninvasive, repeatable, and convenient marker for distinguishing advanced fibrosis from low fibrosis in chronic HBV patients. We believe that the inhibition of HMGB1 may reduce inflammation, apoptosis, and fibrosis, and may stop the progression of chronic liver disease. Furthermore, we are of the opinion that fibrotic progression in chronic liver patients may be prevented by the inhibition of HMGB1, and that this substance can be a new means of following chronic HBV treatment.

HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion

“…It remains unclear whether HMGB1 directly or indirectly led to the cardiac fibrosis. However, some reports indicate that HMGB1 contributes to pulmonary fibrosis [32] and hepatic fibrosis [33]. Our results show that HMGB1 could directly lead to cardiac fibrosis; in addition, IL-17 secreted by Th17 cells also could directly lead to cardiac fibrosis (our unpublished data).…”

Emerging Role of High-Mobility Group Box 1 (HMGB1) in Liver Diseases

“…A prolonged fibrotic response resulting in cirrhosis is also common in both infections, which is accompanied by the appearance of localized hypoxia, rearrangement of tissue architecture (epithelial-mesenchymal transition) and angiogenesis (59). Thus, viral hepatitis confers a risk of developing a chronic infection that can lead to liver fibrosis and eventually evolve into liver cirrhosis and hepatocellular carcinoma (60). Although multiple signaling networks are responsible for coordinating the inflammatory and immune response during virus hepatitis, HMGB1 is critical in initiating and mediating these effects.…”

“…Hepatic stellate cells (HSCs) are quiescent cells in the perisinusoidal space in the liver that facilitate hepatocyte interactions in the process of liver fibrosis via the release of soluble inflammatory factors and the production of ECM (69). HMGB1 is involved in the development and progression of liver fibrosis ( Figure 4B) (60). Recombinant HMGB1 protein remarkably stimulates HSC growth, promotes α-smooth muscle actin (α-SMA) expression and inhibits MMP-2 activity (70).…”

Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes

“…Recently, it has been reported that one of the most well-known DAMPs, namely the afore-mentioned HMGB1, is passively released from necrotic cells (Scaffidi et al, 2002) and secreted from stressed monocytes/ macrophages (Gardella et al, 2002). Many studies have reported that extracellular HMGB1 has pro-inflammatory and immunostimulatory properties and contributes to the pathogenesis of chronic inflammatory and autoimmune diseases, including hepatitis (Albayrak et al, 2010), rheumatoid arthritis (Kokkola et al, 2002), inflammatory bowel disease (McDonnell et al, 2011), acute lung inflammation (Abraham et al, 2000) and atherosclerosis (Porto et al, 2006).…”