Identification of risk factors of development of liver fibrosis and liver tumors in Fontan-associated liver disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17035
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Sagawa Takaomi 東京女子医科大学, 医学部, 助教 (80867929)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: フォンタン関連肝疾患 / 肝腫瘍 / 肝線維化

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.

Free Research Field

消化器内科

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。