Diversity of viral genome mutations during clinical feature of hepatitis B virus infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Watanabe Tsunamasa 聖マリアンナ医科大学, 医学部, 講師 (20338528)
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

肝臓病

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。