Genetic variants of the IgA Fc receptor (FcalphaR, CD89) promoter in chronic hepatitis C patients.

Fc receptor for IgA (FcalphaR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcalphaR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two -311T/C and -142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both -311CC and -142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53-6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14-3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, -311CC and -142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) (< 150,000/microl) (5.1 and 8.5%) compared with 91 patients with normal PLT (> or = 150,000/microl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), -311CC or -142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcalphaR expression affecting IgA-mediated immune responses and/or IgA catabolism.

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

BACKGROUND: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters. METHODS: Two hundred and ninety-five patients were enrolled in the study. The patients received either 6 or 10 million units (MU) of interferon alpha-2b every day for 2 weeks and then three times a week for 22 weeks with a daily dose of either 600 or 800 mg of ribavirin. The treatment response and safety of this treatment were examined. RESULTS: The sustained virologic response (SVR) rates were 26.8% in genotype 1 and 76.5% in genotype 2 (P < 0.001), and 36.1% with the 6 MU group and 45.8% with the 10 MU group (P = 0.09). Multivariate analysis indicated that SVR was associated with genotype 2, HCV RNA <500 kilointernational unit/ml (kIU/ml), and HCV RNA undetectability at week 8 of treatment. CONCLUSION: Our current study showed that a 24-week course of IFN plus ribavirin combination therapy was effective with respect to virologic response in Japanese hepatitis C patients, particularly in patients with HCV genotype 2.

Detection of telomerase activity, telomerase RNA component, and telomerase reverse transcriptase in human hepatocellular carcinoma.

The aim of this study was to estimate the correlation between telomerase activity and the expression of human telomerase RNA component (hTERC), human telomerase reverse transcriptase (hTERT) in patients with hepatocellular carcinoma (HCC), and to analyze the influence of the nucleotide homology of the hTERC template region on telomerase activity. Six HCC patients and two chronic hepatitis patients were enrolled in this study. Telomerase activity was determined using the fluorescence-based telomeric repeat amplification protocol (TRAP) method. Quantification of hTERC and hTERTmRNA was performed using a real-time PCR method. Furthermore, a portion of the hTERC gene was amplified using nested RT-PCR methods. After sub-cloning, the nucleotide sequence of the cloned hTERC that contained the template region was determined. Telomerase activity and hTERTmRNA was detected in all cancerous tissues, while hTERC was present in both tumorous and non-tumorous lesions. The level of telomerase activity correlated with expression of hTERTmRNA, but not that of hTERC. The nucleotide sequence of cloned hTERC was similar in both tumorous and non-tumorous lesions. The expression of hTERT may be a definitive factor in the activation of telomerase in hepatocarcinogenesis.