[Show abstract][Hide abstract]ABSTRACT: Objective:
To identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).
A total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014.All participants were Chinese Han residing in Shanghai and the surrounding areas.The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434).History of hepatitis B infection and HCC,as well as clinical data from serological,imaging and pathological examinations were collected for analysis.SPSS software,version 19.0,was used for all statistical comparisons.
Single factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex,age of 50 years or more,family history of HCC,alcohol consumption,fatty liver,detectable levels of hepatitis B virus (HBV) DNA,and history of HBV infection without effective antiviral treatment.Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005,odds ratio [OR] =1.766),history of alcohol consumption (P =0.002,Or = 2.570),family history ofHCC (P =0.014,Or = 2.268),fatty liver (P =0.023,Or = 3.390),and history of HBV infection without effective antiviral treatment (P less than 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014,Or = 2.537),family history ofHCC (P =0.037,Or = 3.339) and fatty liver (P =0.018,Or = 11.646).
Risk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC,fatty liver,and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC,and fatty liver disease,were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.
No preview · Article · Sep 2015 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
[Show abstract][Hide abstract]ABSTRACT: To determine the potential of the high mobility group box-1 protein 1 (HMGB1) to activate Toll-like receptor 4 (TLR4) signaling in hepatic stellate cells (HSCs) and investigate the subsequent transition of HSC towards the inflammatory phenotype. Three immortalized mouse HSC cell lines, wild-type (JS1), TLR4-/- (JS2) and MyD88-/- (JS3), were subcultured in plates and divided into groups of normal control (untreated), postive control (lipopolysaccaride, LPS treatment), and experimental (HMGB1 treatment). All groups were transfected with luciferase reporter plasmids carrying responsive elements for either the nuclear factor-kappa B (NF-kB) or activator protein-1 AP-1 transcription factors. Following stimulation with normal saline, LPS (100 ng/mL) or HMGB1 (100 ng/mL), the activation of NF-kB or AP-1 was detected by a dual-luciferase reporter assay system. The induction of monocyte chemotactic protein-1 (MCP-1) transcription was determined by measuring the mRNA levels using real time quantitative reverse transcription PCR (qRT-PCR). The secreted protein levels of MCP-1 were determined by enzyme-linked immunosorbent assay (ELISA) of the culture supernatants. Activation of NF-kB- and AP-1-responsive reporters was significantly up-regulated in JS1 cells treated with HMGB1 or LPS, and the activation was coincident with markedly up-regulated transcription and secretion of MCP-1. However, HMGB1 and LPS treatment produced no responsive of the NF-kB and AP-1 reporters, and no increase in expression or secretion of MCP-1, in JS2 or JS3 cells. As an endogeous ligand of TLR4, HMGB1 may activate TLR4 signaling and the TLR4-mediated inflammatory response of HSC.
No preview · Article · Aug 2012 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
[Show abstract][Hide abstract]ABSTRACT: A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.
No preview · Article · Mar 2011 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology