Chronic hepatitis B virus (HBV) infection in children: 25 years' experience.

Whereas e-seroconversion represents the loss of hepatitis B e-antigen (HBeAg) followed by gain of antibody to HBeAg (anti-HBe), 'inactive chronic infection' extends this concept to include e-seroconversion with decreased serum viral load and biochemical remission. These events must be well-characterized before treatment outcomes can be evaluated. We examined the rates of e-seroconversion and achievement of inactive chronic infection among children with chronic HBV infection. Children who were HBsAg positive >6 months were identified retrospectively between 1983 and 2008 from the Hospital for Sick Children Liver Clinic. Inactive chronic infection was defined as loss of HBeAg, serum ALT ≤40 IU/mL, and HBV DNA <10(6 ) IU/mL. Both e-seroconversion and achievement of inactive chronic infection were characterized using survival analysis. The effect of transmission route, treatment, age at diagnosis, ethnicity, gender and baseline ALT on these rates was evaluated with univariate and multiple regression. Of 252 HBeAg-positive cases, 59.9% had HBV-infected mothers, 77% were Asian, and 33 received interferon-α. Untreated children were younger at last follow-up (mean 14.5 vs 17.6 years), had lower ALT (median 60 vs 116 IU/mL) and had shorter follow-up (6.6 vs 9.1 years, all P < 0.002) compared to treated children. Crude e-seroconversion rate was 41.7% over 0.5-19.1 years of follow-up, and this was not affected by transmission route (P = 0.93), gender (P = 0.62) nor treatment (P = 0.08). 49% achieved inactive chronic infection by age 19 years. Being non-Asian, age at diagnosis<3 years, and ALT ≥40 IU/mL were associated with a higher rate of e-seroconversion and achieving inactive chronic infection (P < 0.0001). Almost 50% of children achieved inactive chronic infection by early adulthood.

Kallikrein gene downregulation in breast cancer.

Recent evidence suggests that many members of the human kallikrein gene family are differentially regulated in breast cancer and other endocrine-related malignancies. In this study, we utilised the serial analysis of gene expression (SAGE) and expressed sequence tag (EST) databases of the Cancer Genome Anatomy Project (CGAP) to perform in silico analyses of the expression pattern of the 15 human kallikrein genes in normal and cancerous breast tissues and cell lines using different analytical tools such as Virtual Northern blotting, Digital Differential Display and X-profiler. Our results indicate that at least four kallikrein genes (KLK5, 6, 8, 10) are downregulated in breast cancer. Probing eight normal and 24 breast cancer SAGE libraries with gene-specific tags for each of the above kallikreins indicated moderate-to-high expression densities in normal breast (27-319 tags per million; tpm, in two to five out of eight libraries), compared to no or low expression (0 - 34 tpm in zero to two libraries out of 24) in breast cancer. These data were verified by screening the EST databases, where all mRNA clones isolated for these genes, except for one in each, were from normal breast libraries, with no clones detected from breast cancer tissues or cell lines (with the exception of KLK8). X-profiler comparison of two pools of normal and breast cancer libraries further verified the presence of significant downregulation of expression levels of 4 of the kallikreins genes (KLK5, 6, 10, 12). We experimentally verified the downregulation of these four kallikreins (KLK5, 6, 8, 10 and 12) by RT - PCR analysis.