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本帖最后由 风雨不动 于 2012-4-14 15:54 编辑
AASLD 2010:
368.Identification of patients at risk for the development of hepatocellular carcinoma in chronic hepatitis B and assessment of the impact of nucleoside analogue therapy on risk reduction: Evaluation of the current treatment guidelines and proposal of novel criteria by data mining analysis.
M. Kurosaki; N. Tamaki; Y. Yasui ; T. Kuzuya ; K. Tsuchiya; Y. Asahina ; N. Izumi
Background and aims: The criteria for the treatment of chronic hepatitis B virus (HBV) infection in the current guidelines are based on hepatitis B e antigen (HBeAg) status, HBV DNA levels, and alanine aminotransferase. Since it is not known whether these criteria could sufficiently cover patients at risk for developing hepatocellular carcinoma (HCC), we validated the current guidelines based on the natural history of a cohort of chronic hepatitis B. Using data mining analysis, we also analyzed other risk factors for HCC and the efficacy of nucleoside analog therapy for the prevention of HCC.
Methods: A cohort of 613 patients with chronic hepatitis B at a single regional hospital in Japan was studied. Patients who were positive for HBeAg and had persistently normal value of ALT (immune-tolerant) were not included. Patients were screened for HCC for the average period of 5.5 years. The guideline criteria for antiviral treatment were applied to this cohort to evaluate their efficacy in identifying patients at risk for HCC. Factors associated with the development of HCC were analyzed by data mining analysis using the IBM-SPSS Modeler 13 software. Data from 197 patients on long-term nucleoside analogue therapy was applied on this model to evaluate the efficacy of antiviral therapy in preventing HCC.
Results: The 5 year cumulative incidence of HCC in this untreated cohort was 12%. According to the guideline criteria, only 7% of the patients who developed HCC had indication for antiviral therapy. Data mining analysis revealed that age older than 40, platelet lower than 150 (109/L), serum HBV DNA higher than 5.8 (log copies/ml), and double mutations in basic core promoter 1762/1764 were significant risk factors for HCC. The 5 year cumulative incidence of HCC in patients fulfilling 0, 1, 2-3, and 4 of these criteria was 0%, 0-5%, 14%, and 50%, respectively. If age and platelet counts were included in the criteria, sensitivity of identifying patients at risk for HCC improved to 83%. If mutations in basic core promoter 1762/1764 were also included, the sensitivity further improved to 91%. By long-term nucleoside analogue therapy, the 5 year cumulative incidence of HCC reduced by 9-41% among patients at high risk.
Conclusions: The current treatment guidelines for chronic hepatitis B excluded significant proportion of patients at high risk for HCC. Novel criteria based on age, platelet counts, serum levels of HBV DNA, and basic core promoter 1762/1764 mutations covered over 90% of patients at high risk. Nucleotide analogue therapy significantly reduced the incidence of HCC among these high risk patients.
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发表于 2010-11-7 09:49
