Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) plays a pivotal role in regulating T cell activation, which is believably critical for the outcome of hepatitis B virus (HBV) infection. The expression and function of CTLA-4 may be affected by gene polymorphisms. This study investigated the influence of CTLA-4 polymorphisms on disease susceptibility in Chinese Han patients with chronic HBV infection. CTLA-4 +49A/G and -318C/T polymorphisms were evaluated by DNA amplification with polymerase chain reaction followed by the restriction fragment length polymorphism analysis. The patients with chronic HBV infection had higher frequencies of genotype AA and allele A of CTLA-4 +49A/G polymorphism. The haplotype +49A-318C was significantly over-represented (P < 0.001) and haplotype +49G-318C under-represented (P = 0.006) in the patients. The +49GG genotype was more frequent (P = 0.009) and +49A allele was less frequent in patients with lower ALT levels (P = 0.012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients.
CTLA4 +49GG genotype was associated to lower TNF-α and IFN-γ levels in patients with chronic HBV infection but this association was diminished by haplotype formation with -318C/T alleles, indicating that the influence of CTLA4 -318C/T and +49A/G polymorphisms on the susceptibility and disease progress of chronic HBV infection may not be effectuated by affecting TNF-α and IFN-γ secretion.
Laminin participates in regulating immune response in addition to being a biomarker of liver fibrosis. Lamivudine has been shown to be able to restore cytotoxic T-cell response in chronic hepatitis B. In this study, fifty-two patients with HBeAg-positive chronic hepatitis B received lamivudine treatment for more than 12 months. Serum laminin levels were determined at baseline and during treatment and analyzed regarding treatment responses at the end of 12 months of therapy. The results showed that laminin levels at 12 months of treatment in patients who lost HBeAg were significantly lower compared with baseline (P = 0.001). The baseline laminin levels were higher in HBeAg seroconversion group than those without seroconversion (P = 0.037). Compared with baseline, the levels of serum laminin in HBeAg seroconversion group showed significant decrease (P = 0.001). It is concluded that higher pretherapy and significant decrease during the first 12 months of therapy in laminin levels may associate with HBeAg seroconversion in chronic hepatitis B patients treated with lamivudine, indicating the possible novel information of laminin for clinical reference.
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