I Sghaier1, S Zidi1, L Mouelhi2, E Ghazoueni3, E Brochot4,5, W Y Almawi6, B Y Loueslati6. 1. a Faculty of Sciences of Tunis , University of Tunis El Manar , Tunis , Tunisia. 2. b Hepato-Gastro-Enterology department , Charles Nicolle Hospital , Tunis , Tunisia. 3. c Laboratory of Immunology , Military Hospital of Tunis , Tunis , Tunisia. 4. d Department of Virology , Amiens University Medical Centre , Amiens , France. 5. e Virology Research Unit, EA 4294 , Jules Verne University of Picardie , Amiens , France. 6. f Faculty of Sciences of Tunis, Laboratory of Mycology , University of Tunis El Manar , Tunis , Tunisia.
Abstract
BACKGROUND: Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC. MATERIALS AND METHODS: We recruited 174 HCV-infected patients, 100 HBV-infected patients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest. RESULT: The TLR3 rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4 rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3 rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4 rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease. CONCLUSION: TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.
BACKGROUND:Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC. MATERIALS AND METHODS: We recruited 174 HCV-infectedpatients, 100 HBV-infectedpatients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest. RESULT: The TLR3rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease. CONCLUSION:TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.
Authors: Wen-Yue Liu; Mohammed Eslam; Kenneth I Zheng; Hong-Lei Ma; Rafael S Rios; Min-Zhi Lv; Gang Li; Liang-Jie Tang; Pei-Wu Zhu; Xiao-Dong Wang; Christopher D Byrne; Giovanni Targher; Jacob George; Ming-Hua Zheng Journal: J Clin Transl Hepatol Date: 2021-02-22