| Project/Area Number |
16K09379
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | B型肝炎ウイルス / ウイルス遺伝子変異 / 急性肝炎 / 肝細胞癌 / 次世代シークエンス解析 / ウイルス遺伝子多型 / APOBEC / 肝臓学 |
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| Outline of Final Research Achievements |
Nucleot(s)ide analogues therapy cannot completely eliminate and inhibit the development of hepatocellular carcinoma (HCC). We investigated diversity of viral genome mutations during clinical feature of hepatitis B virus infection. A total of 20 acute hepatitis B (AH-B) cases were collected. For applying next-generation sequencing platform, we prepared pan-genotypic primers and have been working. Next, we investigated the presence of viral genome mutations representing important predictive markers for HCC in patients with chronic HBV infection. In the cross-sectional analysis, 445 patients were divided according to HCC history and the influence of the viral protein markers. Patients with a history of HCC were found frequently in the low HBsAg group and high HBcrAg group, indicating that preS/S mutants could cause an imbalance of surface protein synthesis resulting in intracellular accumulation and extracellular decrease of HBsAg proteins, and leading to hepatocyte carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
現在の治療戦略では、B型肝炎ウイルス（HBV）根絶に不可欠なcccDNAを制御することはできず、HBV関連肝細胞癌（HCC）発症も制御できず、HCC早期発見の手段も限定的である。本研究は、細胞内におけるHBVゲノム変異ないし組み換えに着目した治療戦略の可能性を模索し、その結果としてHBs抗原タンパクの変異がHCC発症と関連する可能性を見出した。従来から提唱されていたHCCリスク集団とは異なり、新たなHCCリスクのサロゲートマーカーに繋がる可能性があり、社会的意義は大きく、さらに宿主ゲノムへのHBVインテグレーション解析の重要性が再認識されたことから、学術的意義も高いと考える。
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