Identification of risk factors of development of liver fibrosis and liver tumors in Fontan-associated liver disease
| Project/Area Number |
20K17035
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Sagawa Takaomi 東京女子医科大学, 医学部, 助教 (80867929)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | フォンタン関連肝疾患 / 肝腫瘍 / 肝線維化 / 肝臓がん / 肝繊維化 |
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| Outline of Research at the Start |
Fontan手術は先天性心疾患に対する心臓の修復手術であり、長期経過でFontan associated liver disease (FALD)と肝細胞癌 (HCC)を含む肝腫瘍を合併する。線維化の程度の把握に難渋するため、非侵襲的なマーカーの検討が急務である。今回我々は、1.肝生検組織結果で得られた肝線維化の程度と各種血清線維化マーカー及び線維化スコアリングシステムを対比し、線維化を評価する最適なマーカーを同定する。2.血液検査値、心エコー検査、心臓カテーテル検査値を肝硬変例およびHCC例で検討し、肝線維化進行ならびに肝発癌リスク因子を同定することを目的として研究を行う。
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| Outline of Final Research Achievements |
The progression of liver disease due to hepatic congestion, known as FALD, after Fontan surgery. Total 154 patients (66 men, 42.9%) developed liver disease after Fontan procedures. HCC was diagnosed in 15 (9.7%) at a median age of 34 years (range, 21-45 years). Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. The hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score (MELD-XI, p = 0.06) tended to be higher in FALD-HCC patients. Patients with T-BIL levels ≧2.2 mg/dL, HA levels ≧ 55.5 ng/mL, and MELD-XI scores ≧18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. The complication of polysplenia (HR: 10.915) and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
多脾の合併とMELD-XIスコア高値例は、FALD患者においてHCC発症と死亡を予測する可能性があると考えられ、FALDの非侵襲的な肝線維化マーカーを用いて、肝腫瘍発症のリスク患者の絞り込みが可能となると考えられます。また、中心静脈圧を下げるなどの治療介入により肝疾患の進行や肝発癌が抑止できるか、今後さらに検討する必要があります。
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Report
(4 results)
Research Products
(17 results)
