黒田 英克, 柿坂 啓介, 及川 隆喜, 小野寺 美緒, 滝川 康裕

Hidekatsu KURODA, Keisuke KAKISAKA, Takayoshi OIKAWA, Mio ONODERA, Yasuhiro TAKIKAWA

岩手医科大学内科学講座消化器内科肝臓分野

Division of Hepatology, Department of Internal Medicine, Iwate Medical University

キーワード : acute hepatitis, liver stiffness, Virtual touch quantification, velocity of shear wave, prognosis

急性肝炎において肝硬度が上昇するという報告が散見される．肝細胞壊死と炎症に起因すると推測されるが，未だ不明瞭な点も多いのが現状である．本稿では，急性肝炎におけるVTQ（virtual touch quantification）を用いた肝の剪断弾性波伝播速度（velocity of shear wave: Vs）測定の有用性を検討するとともに，肝硬度と病理所見との対比を中心に基礎的検討を行ったので報告する．急性肝疾患51例の入院時Vsの平均値±標準偏差は，急性肝炎：2.03 ± 0.55 m/s，急性肝炎重症型：2.54 ± 0.56 m/s，劇症肝炎：3.65 ± 0.86 m/sで，重症度に伴い有意に高値を示した（p ＜ 0.001）．劇症化予知に関するVTQのAUCは0.893で，cut off値を3.14 m/sとすると感度80.0％，特異度93.5％であった．生存例ではVsの有意な経時的低下を認めた（p ＝ 0.003）．D-galactosamine投与ラット肝障害モデルを用い，肝硬度と炎症や壊死の程度とを比較すると，肝障害度別のVsは，G0: 1.07 ± 0.05 m/s，G1: 1.27 ± 0.09 m/s，G2: 1.54 ± 0.23 m/s，G3: 1.99 ± 0.16 m/sで，病理変化に伴いVsの有意な上昇を認めた（p ＜ 0.01）．急性肝炎では肝細胞壊死と炎症の影響でVsが上昇する．Vsは重症度や病態を反映する予後予測指標で，経時的計測からより正確に予後推定が可能であり，移植適応判定にも応用できる可能性が示唆された．

Background and Aim: We measured liver stiffness (LS) in patients with acute liver disease (ALD) using Virtual touch quantification (VTQ) and investigated the usefulness of measuring LS for predicting the prognosis of ALD patients. Materials and Methods: From April 2010 to December 2012, we evaluated 51 patients with ALD. The subjects included 32 patients with acute hepatitis (AH), 14 patients with acute hepatitis severe form (AH-s), who had no hepatic encephalopathy despite plasma prothrombin time of <40%, and five patients with fulminant hepatitis (FH) diagnosed according to the criteria of the Japanese Study Group. The relationships among velocity of shear wave (Vs), clinical diagnosis, liver function tests, and prognosis were evaluated. Receiver operating characteristic (ROC) analysis was performed to investigate whether VTQ exhibits potential usefulness for the early prediction of FH. In addition, we investigated the relationship between LS and the grade of liver damage using D-galactosamine-induced acute hepatitis in rats. Results: Vs on admission was 2.03 ± 0.55 m/s, 2.54 ± 0.56 m/s, and 3.65 ± 0.86 m/s in the AH, AH-s, and FH groups, respectively. Vs was significantly higher in the FH group than in the other groups (p<0.001). The area under the ROC curve for predicting FH was 0.893 (sensitivity 80.0, specificity 93.5). Vs was significantly increased in the non-survivors (n=4), while it decreased in survivors (n=47) (p=0.003). Vs by grade of liver damage was G0: 1.07 ± 0.05 m/s, G1: 1.27 ± 0.09 m/s, G2: 1.54 ± 0.23 m/s, and G3: 1.99 ± 0.16 m/s. Vs increased significantly with the severity of hepatic inflammation and necrosis (p<0.01). Conclusion: Vs measured by VTQ reflects the severity of liver damage, and the serial changes in Vs predict the prognosis of ALD patients. Vs is an early and precise biomarker of FH.