Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n ‫؍‬ 182) or placebo (n ‫؍‬ 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log 10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log 10 reduction at week 34 and 2.02 log 10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B. (

A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.

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Using messenger RNA (mRNA) differential display, we identified a single complementary DNA (cDNA) fragment (HG23T1) that was over-expressed in a hepatocellular carcinoma (HCC) specimen. We cloned the full-length HG23T1 gene by the rapid amplification of cDNA end (RACE) polymerase chain reaction (PCR) method. It perfectly matched the gene encoding human ribosomal protein L36a (RPL36A also referred to as RPL44). RPL36A mRNA was preferentially over-expressed in 34 of 40 HCC cases (85%, P < .001) and in all of 8 HCC cell lines. Ectopically over-expressed L36a ribosomal protein localized in the nucleoli of cells, and this localization seemed to be controlled by the N-terminal or the internal tetrapeptide consensus with its adjacent N-terminal domain. Over-expression of L36a led to enhanced colony formation and cell proliferation, which may have resulted from rapid cell cycling, and an antisense cDNA effectively reversed these alterations. In conclusion, RPL36A plays a role in tumor cell proliferation and may be a potential target for anticancer therapy of HCC. (HEPATOLOGY 2004;39:129 -138.) H epatocellular carcinoma (HCC) is a major malignancy with an increasing incidence worldwide. 1 The major risk factors for development of HCC are cirrhosis, chronic viral hepatitis B and C, exposure to aflatoxin, alcohol, and/or iron overload. HCCs are highly resistant to chemotherapeutic agents and radiotherapy. 2 Despite a variety of treatment options, including surgical resection, chemoembolization, percutaneous injection of ethanol, radiofrequency thermal ablation, and liver transplantation, the prognosis for HCC is poor. [3][4][5] Thus, the need to discover effective therapeutic molecules to suppress the growth of HCC is urgent. One approach is to find target genes and their molecular products and understanding how genetic and molecular changes can lead to cancer development through multistep carcinogenesis.Altered gene expression caused either by mutations or by changes in the regulatory characteristics of HCC compared with corresponding nontumor tissues have been reported. 6 -8 Such alterations can occur in various cell cycle-related oncogenes, such as c-myc, K-ras, and H-ras, and/or in tumor suppressor genes, such as retinoblastoma and p53. 9 -12 In addition, glutamine synthetase, alfa-fetoprotein (AFP), the insulin receptor substrate-1-like gene, cyclin D1, MAGE-1, HIP/PAP, and CD24 have been reported to be over-expressed during hepatocarcinogenesis. [13][14][15][16][17][18][19] However, these genetic changes do not precisely reflect the biologic nature or clinical characteristics of all HCCs. Previously, we identified and reported genes that were differentially expressed in HCC cells using the differential-display polymerase chain reaction (PCR) method. 20 Among them, we focused preferentially on an up-regulated gene in human HCC in comparison with the nontumor surrounding tissues. This gene later proved to encode the ribosomal protein L36a (RPL36A) protein, which is localized in the nucleolus.The biogenesis of eukary...