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Summary: The treatment option in chronic hepatitis B (CHB) patients with persistent low‐level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)‐positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg‐positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03‐19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24‐9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04‐3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41‐4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development. [ABSTRACT FROM AUTHOR]

Recent studies have shown that some mammalian micro RNAs (mi RNAs) play a role in antiviral defence. However, little is known about the role of mi RNA-323b in hepatitis B virus ( HBV)-host interaction. We explored whether single nucleotide polymorphism ( SNP) of mi RNA-323b affects HBV replication in a Korean HBV cohort. Genotyping was performed in a total of 1439 subjects composed of 404 spontaneously recovered ( SR) subjects as normal controls and 1035 chronic carriers ( CC) of HBV who were further classified into 313 patients with chronic hepatitis, 305 patients with liver cirrhosis and 417 patients with hepatocellular carcinoma. To confirm the effect of SNP of mi RNA-323b on HBV replication in vitro, Hep AD38 cells were transfected with mi RNA-323b wild type or mi RNA-323b SNP plasmid vectors, and HBV replication was induced for 5 days. HBV DNA was isolated and quantified using real-time PCR. The polymorphism rs56103835 C> T in the pre-mi RNA region of mi RNA-323b revealed significant minor allele frequency (0.273). rs56103835 C> T SNP showed significantly affect persistence of HBV in CC group compared with SR group (OR = 1.29, P = 0.009 in a codominant model; OR = 1.29, P = 0.03 in a dominant model; and OR = 1.78, P = 0.03 in a recessive model). In vitro, the total intracellular HBV DNA content was significantly reduced by mi RNA-323b wild-type plasmid vector transfection ( P = 0.014). The polymorphism of mi RNA-323b was significantly associated with persistence of HBV by the enhancement of HBV replication ( P = 0.021). Our findings provide a novel perspective on the role SNP of mi RNAs in host-virus interactions in HBV infection. [ABSTRACT FROM AUTHOR]

Previous studies showed that several genetic polymorphisms might influence the clinical outcome of chronic hepatitis B virus (HBV) infection, including HBV clearance or development of hepatocellular carcinoma (HCC). The aim of this study was to determine whether polymorphisms of the transforming growth factor-alpha (TGF-alpha) gene are associated with clinical outcome of HBV infection. A total of 1096 Korean subjects having either present or past evidence of HBV infection were prospectively enrolled between January 2001 and August 2003. Among 16 genetic variants in TGFA gene, nine variants were genotyped using TaqMan assay and the genetic association with HBV clearance and HCC occurrence was analysed. Statistical analyses revealed that TGFA+103461T>C, TGFA+106151C>G and TGFA-ht2 were marginally associated with clearance of HBV infection. However, only TGFA-ht2 retained significance after multiple correction (OR = 0.39, P(corr) = 0.007 in recessive model). Although no variants were significant after multiple correction, TGFA+88344G>A and TGFA+103461T>C were weakly associated in recessive model in the analysis of HCC occurrence. In addition, Cox relative hazards model also revealed that TGFA+88344G>A was associated with onset age of HCC occurrence in subjects (RH = 1.46, P(corr) = 0.04). TGF-alpha polymorphisms might be an important factor in immunity, progression of inflammatory process and carcinogenesis, which explains the variable outcome of HBV infection at least in part. Further biological evidence is warranted in the future to support these suggestive associations.