Analysis of the precore and core promoter DNA sequence in liver tissues from tients with hepatocellular carcinoma

To investigate the role of mutant hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC), 20 patients with HCC were studied for precore and core promoter mutations in tumorous and nontumorous tissues. The precore and core promoter region was amplified and analyzed by direct sequencing. Among the 20 tumorous and nontumorous tissues, precore mutant HBV was found in 12 (60%) and 18 (90%), respectively. Of the 12 tumorous tissues with precore mutant, nine tissues had a single mutation (1896) and one tissue had another single mutation (1899). The remaining two tissues had a double mutation (1896 and 1899). A single mutation (1896) and a single mutation (1899) were found in 11 and two of the 18 nontumorous tissues with precore mutant, respectively. Among 20 tumorous and nontumorous tissues, HBV with a C to T mutation at nucleotide (nt) 1846 was detected in six and eight, respectively, and was associated with the virus carrying a mutation (1896 or 1899) except in two tumorous tissues. Mutations at nt 1762 and 1764 in core promoter were observed in 16 (80%) tumorous tissues and 18 (90%) nontumorous tissues. Mutations in the precore and core promoter region were found frequently in nontumorous tissue and in tumorous tissue (18/20 and 12/20 in precore region, 18/20 and 16/20 in core promoter respectively). The high prevalence of precore and core promoter mutations in liver tissue from patients with HCC suggests that these mutations may contribute to the development of HCC.

Aspectos inmunológicos e inmunogenéticos de la hepatitis B. Evolución histórica

The most common cause of viral hepatitis in USA is the hepatitis B virus, and since 1983 is more common than hepatitis A. In 1980 a serum derived hepatitis B vaccine was evaluated and introduced to clinical practice. The fear of HIV transmission leads to the development in 1984 of a recombinant vaccine produced in the yeast Saccharomyces cerevisae through DNA recombinant technics. Both vaccines have been proved effective and safe, with seroconversion in 85-96 percent of homosexual males and 96-98 percent of healthy adults. Several recent studies have shown that 5-10 percent of healthy adults fail to respond to the vaccine, even after additional dosages. The mechanism for this lack of Anti-HBs response has been extensively studied by several groups and associated to the major histocompatibility antigens in relationships with T lymphocytes responses to specific antigens. Recent studies have demonstrated that the lack of response to the HBsAg is due to a mechanism of peripheral restriction previously shown by Crave, Alpert et al, and not related to gene suppression nor through CD8T+ cells. The absence of response is secondary to the macrophage-antigen interaction and CD4T+ cells and is also multifactorial. Studies in caucasian populations have shown that poor responders to hepatitis B vaccines have certain haplotypes such as: B8, Dr7, Dr3, Dr7, Dr4 and Dr7+B8. Alpert et al have shown for the first time in humans that persons homozygous for extended haplotype HLA B8-DR3-SCO1, have a poor response to a HBsAg and is recessive. Only one haplotype is sufficient to have an adequate Anti-HBs response. Sasasuki et al, in contrast have shown that Japanese haplotype HLA-BW54-DR4-DRW53 and DQW3 is associated to poor response to HBsAg, and is dominant, they also suggest that lack of response depends of an immunosupresion gene through CD8 cells. Finally our results suggest that no responders have a specific defect located to the level of helper T Cells stimulation, and its not mediated through immunosupresion through CD8T cells.