Alpha-fetoprotein (AFP) is a marker of the presence of hepatocellular carcinoma (HCC), but is also elevated in advanced chronic hepatitis B. The detection and usage of AFP tests need to be improved. A cohort of 101 patients with advanced chronic hepatitis B and elevated AFP values was treated with entecavir (ETV) or peginterferon-alpha2a. ETV was more effective in reducing AFP levels; mean time to AFP normalization was 11.9 weeks after ETV treatment initiation vs 22.3 weeks in peginterferon treated patients (P = 0.000). An additional cohort of 93 hepatitis B virus (HBV) cirrhotic patients with elevated AFP were treated with ETV prospectively and maintained under intensive surveillance. HCC developed in 16 (17.2%) patients in whom the strongest independent predictor was a continued AFP rise in spite of ongoing treatment. In this context, nodules of sizes 10-14 mm and 15-20 mm were detected in 40% of patients each. In conclusion, HBV cirrhotic patients with rising AFP levels were at very high risk of HCC development. Early detection of minute lesions may be possible by monitoring AFP levels, whilst patients are on treatment in conjunction with enhanced computed tomography examination.
The biological implications of substitutions L60V and I97L in the core (c) gene of hepatitis B virus (HBV) were investigated in order to determine whether they could change the immunogenicity of HBcAg or influence the immune response in mice. Three strains of recombinant adenoviruses--AdHBV-WT, AdHBV-L60V and AdHBV-I97L--containing wild-type or mutant HBV genomes were constructed using the AdEasy system and used to infect BALB/c mice intranasally. Infected mice produced anti-HBc efficiently to comparable levels. IgG1 and IgG2a specific for HBcAg were present in mice sera, and the response was dominated by IgG2a. The lymphocyte proliferative response specific for HBcAg was assessed by [3H]-thymidine uptake. We found that AdHBV-WT induced a stronger T-cell proliferation response than AdHBV-L60V and AdHBV-I97L. In conclusion, the L60V and I97L substitutions had no influence on humoral immune responses, but could downregulate T-cell responses to HBcAg, suggesting that L60V and I97L were immune escape mutants.
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