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Current and future directions for treating hepatitis B virus infection

World Journal of Hepatology 2015年第11期7卷 1541-1552页

作者： akinobu tawada Tatsuo Kanda Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba Univer-sity Graduate School of Medicine

Hepatitis B virus(HBV) persistently infects approximately 350 million people, and approximately 600000 liverrelated deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma(HCC). The persistence of serum hepatitis B e antigen(HBe Ag) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues(NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBe Ag to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate.

关键词： Hepatocellular carcinoma Peginterferon Nucleotide analogue Chronic hepatitis B

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Transcatheter arterial infusion for advanced hepatocellular carcinoma: Who are candidates?

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World Journal of Gastroenterology 2015年第29期21卷 8888-8893页

作者： Eiichiro Suzuki Tetsuhiro Chiba Yoshihiko Ooka Sadahisa Ogasawara akinobu tawada Tenyu Motoyama Naoya Kanogawa Tomoko Saito Masaharu Yoshikawa Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University

AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years(range: 37-82 years). Six patients(6.3%) showedcomplete response and 18 patients(18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good(prognostic index = 0-1; n = 54), intermediate(prognostic index = 2; n = 26), or poor(prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively(P < 0.01). CONCLUSION: Our simple pro

关键词： Hepatocellular carcinoma Interventionalradiology Prognostic factor Survival Transcatheterarterial infusion

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Biological features and biomarkers in hepatocellular carcinoma

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World Journal of Hepatology 2015年第16期7卷 2020-2028页

作者： Tetsuhiro Chiba Eiichiro Suzuki Tomoko Saito Sadahisa Ogasawara Yoshihiko Ooka akinobu tawada Atsushi Iwama Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University Department of Cellular and Molecular Medicine Graduate School of Medicine Chiba University

Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma(HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers.

关键词： Hepatocellular carcinoma Heterogenity Molecular biology Oncology Sorafenib

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