Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis

Abstract

Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model. Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61–2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62–6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18–2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58–5.60, p = 0.001); but, high expression of galectin-4 and −9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36–0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44–0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19–0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37–0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79–4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23–0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15–2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91–27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57–4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61–9.99, p < 0.001). Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.