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.

Serum Galectin-3 in Hepatitis C Virus Infection Declines after Successful Virus Eradication by Direct-Acting Antiviral Therapy

“…Further analysis showed that serum galectin-3 was induced in active HBV infection. According to this study, HCV infected patients even had lower serum galectin-3 than healthy controls [18]. It was also reported that serum galectin-3 did not differ between HCV infected patients and non-infected controls [19].…”

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

“…To date, 15 subtypes of galectins family have been identified in humans, of which galectin-1, -3, and -9 are the most implicated in liver disease. Numerous experimental and clinical study results suggest that galectins play important and diverse roles in fibrogenesis, cellular immunity and inflammatory response, cell cycle regulation, apoptosis, regeneration, and tumorigenesis [ 77 , 78 ].…”

“…A systematic review and meta-analysis by An et al found that serum galectin-3/9 levels correlate with the risk of liver failure and cirrhosis, and high galectin-1/3 expression is associated with poor prognosis in HCC. However, the evidence for galectin involvement in chronic liver disease remains controversial, and the impact of galectin-3 levels on NAFLD/NASH is thought to be dependent upon the stage and severity of liver damage [ 78 ]. Hence, modern galectin-targeting drug candidates are intended for use in advanced NASH complicated by liver fibrosis and/or cirrhosis.…”

Galectin-1 in Obesity and Type 2 Diabetes

“…Galectin-1 is involved in key cellular functions related to tissue maturation, homeostasis and remodelling through regulation of cell migration, proliferation, angiogenesis, apoptosis, inflammation, among others [ 1 ]. The interest in galectins in human disease has increased over the recent years, and several comprehensive reviews have previously provided overviews on the effects of galectins in various conditions [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Recently, several galectins, including galectin-1, have also been identified as important for adipose tissue homeostasis, both as regulators of adipose tissue function, and in metabolic disease [ 7 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”