Masakatsu Iwai

Validity of 13C-phenylalanine breath test to evaluate functional capacity of hepatocyte in patients with liver cirrhosis and acute hepatitis

Background : No definitive method for quantitative evaluation of hepatic function has as yet been established.

Ratio of circulating follistatin and activin A reflects the severity of acute liver injury and prognosis in patients with acute liver failure

Background and Aim:  The activin A–follistatin system is known to play a critical role in hepatocyte regeneration during the repair of liver tissue. However, the relationship between blood levels of these compounds and the severity and prognosis of acute liver injury remains unclear. The aim of this study was to evaluate the clinical significance of circulating activin A and follistatin in patients with acute liver disease.

Serum levels of soluble Fas ligand in patients with acute and fulminant hepatitis : relationship with soluble Fas, tumor necrosis factor α and TNF receptor-1

We measured the serum levels of soluble Fas ligand (sFasL) using a newly developed ELISA system in patients with acute hepatitis (AH), acute severe hepatitis (ASH) and fulminant hepatitis (FH). In addition, we also evaluated the relationship between the serum levels of sFasL, soluble Fas (sFas), soluble tumor necrosis factor α (sTNFα), and soluble TNF receptor-1 (sTNFR1). The median serum sFasL level was significantly increased in patients with acute liver disease compared to that in normal subjects; however, there were no significant differences among patients with AH, ASH, and FH. The serum sFasL levels varied according to the cause of hepatitis and were particularly high in patients with hepatitis A viral infection. On the other hand, the median serum sFas level was also significantly increased in patients with acute liver disease compared to that in normal subjects; however, there were no significant differences among patients with the three clinical forms or various causes of hepatitis. The serum sFasL levels decreased rapidly following improvement in liver functions, whereas the serum sFas levels decreased more gradually and remained abnormally high even at follow-up. The serum sFasL levels were not correlated with the levels of serum transaminases or sFas, but were significantly correlated with those of sTNFα (r=0.483, P<0.001) and sTNFR1 (r=0.324, P<0.05). On the other hand, serum sFas levels were significantly correlated with those of sTNFR1 (r=0.319, P<0.05) alone. Our results suggest that the serum sFasL level increases in the acute phase of hepatitis and the level varies according to the cause of hepatitis. Our findings also suggest that the Fas-FasL system and cytokine networks may be closely associated with early process of hepatic necrosis.

Clinical features of fulminant hepatitis: An etiological analysis.

当教室にて1981年から1993年までの13年間に経験した劇症肝炎40例を対象に,輸血スクリーニング法の確立した時期を考慮して,1989年以前と1990年以降に分けてその成因を比較し,成因ウイルス別にみた臨床像を検討した.成因は,ウイルス性35例,薬剤性1例,自己免疫性4例であり,ウイルスの重感染例は認めなかった.1989年以前はB型68%(輸血後例44%),N型16%であったが,1990年以降はB型20%(輸血後例0%),N型47%とB型の明らかな減少とN型の増加傾向を認めた.C型の臨床像はB型に比して,1)肝炎発生から脳症発現までの期間が長い,2)脳症発現時の総ビリルビン値が高い一方,PT(%)が比較的保たれている,3)血清トランスアミナーゼの低下が遷延している,4) AFPの反応が低い,などの特徴を認めた.N型はB型とC型の中間の臨床像を呈しており,その成因については今後さらに検討が必要と考えられた.

Decreased brain concentrations of choline and acetylcholine in mice with thioacetamide-induced acute liver failure

To investigate the alteration of the cholinergic neurotransmitter system in hepatic encephalopathy (HE), we measured the concentrations of choline (Ch) and acetylcholine (ACh) in the brain of mice with thioacetamide (TAA)-induced acute liver failure using a high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The concentrations of Ch and ACh in TAA-treated mice decreased in most regional brain areas as compared to control mice. In particular, Ch significantly decreased in the cortex (P < 0.05), hippocampus (P < 0.01), hypothalamus (P < 0.05), midbrain (P < 0.01) and medulla oblongata (P < 0.01). Similarly, ACh significantly decreased in the striatum (P < 0.01), hippocampus (P < 0.01), midbrain (P < 0.01) and medulla oblongata (P < 0.01). Our findings suggest that the suppression of the cholinergic neurotransmitter system may play a role in the pathogenesis of HE in acute liver failure.