Published papers

ヒトの腸管内には無数の細菌が腸内細菌叢を形成しており、宿主の免疫系に多大な影響を与えている。これまでの研究で、炎症性腸疾患は遺伝的素因、免疫学的機序の異常とともに腸内細菌を含んだ環境因子が関連した多因子疾患であることが示唆されている。近年、次世代シーケンサーを用いた腸内細菌の解析により、炎症性腸疾患と腸内細菌叢の乱れ、すなわちdysbiosisが関連していることが明らかになってきた。dysbiosisが腸炎を惹起することが示唆されており、また特定の細菌が腸炎の惹起・制御に関与していることも明らかとなってきた。これらの知見から腸内細菌に着目し働きかけることで腸炎を改善させる治療に期待が集まってきている。近年、dysbiosisを強力に是正する治療として糞便微生物移植が注目されており、炎症性腸疾患の新たな治療として世界中で臨床試験が開始されている。(著者抄録)

栄養指導によるアルコール性肝障害(ALD)の進展予防について検討した。ALDを住民検診や定期健診で指摘された男性48例を対象とした。栄養相談を拒否した群29例は、受けた群19例より比較的若年で、BMIが高く、独身や単身赴任が多く、多忙や自分で節酒できるなど依存症の否認に近い理由で拒否する例が多かった。ALTは拒否群で高く、γGTPは受講群で高かった。管理栄養士による栄養相談を受けたALD群で、肝機能ならびにTGの改善率が高かった。中等度飲酒群、非アルコール性脂肪性肝障害(NAFLD群)における栄養相談を受けていない群では、肝機能、TGの改善はほとんどみられなかった。栄養相談を受けた中等度飲酒例群ではAST、ALT、γ-GTPとも改善を認め、非アルコール性脂肪性肝障害群ではALTのみ改善を認めたが、改善の程度はALD群より少なかった。TGの改善もALD群で最も顕著であった。

Routine second-look endoscopy after gastric endoscopic submucosal dissection (ESD) remains controversial. The aim of the present study was to systematically evaluate the efficacy of second-look endoscopy for gastric ESD. PubMed, the Cochrane library, and the Igaku-chuo-zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data were combined to calculate a pooled odds ratio (OR) for developing post-ESD bleeding. The database search yielded three randomized trials (854 patients). Compared with second-look endoscopy, the pooled OR for post-ESD bleeding without second-look endoscopy was 0.69 (95% confidence interval [CI]: 0.38-1.26, P = 0.228), without significant heterogeneity. There were no significant differences between second-look endoscopy and no second-look endoscopy with regard to large tumor size (>20 mm). This systematic review and meta-analysis showed that second-look endoscopy had no advantage for the prevention of post-ESD bleeding in patients without a high risk of bleeding.

Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.

We present the case of a 25-year-old woman at 16 weeks of gestation who presented with non-comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine doses (50mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non-comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.

炎症性腸疾患の原因はいまだ不明な点が多いが,遺伝学的因子,環境因子,免疫学的な因子などの複合的な因子が関与していると考えられている.特に腸内細菌との関係については,腸内細菌叢解析の進歩によりプロバイオティクスを中心とした腸内細菌をターゲットとした治療法が注目されてきている.Bacteroides fragilis,Clostridium butyricum,Fusicatenibacter saccharivoransなどの腸内細菌は,IL-10を介して腸炎抑制効果を有することより,治療応用や疾患活動性評価に有用である可能性が期待されている.(著者抄録)

症例は42歳、男性。HCV抗体陽性を指摘され当院紹介された。体質性黄疸を指摘されていたが、肝機能異常を認めたことはなかった。一般血液検査ではTB、ALT以外に異常は認めなかった。HCVは1型でウイルス量7.1Log IU/mLのため、ペグインターフェロン+リバビリン+シメプレビル3剤併用療法を開始した。投与前血清総ビリルビン値(TB)2.5mg/dl、直接ビリルビン値(DB)0.1mg/dLであったが、3週目にTB 8.1mg/dLと上昇した。肝機能は正常化しているため薬剤は減量せず継続し、4週目にはTBも5.1mg/dLと低下し、HCV-RNAも陰性化した。24週目はTB 2.7mg/dlと投与前値に回復した。3剤併用療法では、一過性のTB上昇が報告されている。体質性黄疸合併慢性C型肝炎に対し3剤併用療法を施行し、黄疸の増強後に回復を認めた症例を経験したので報告した。間接ビリルビン優位の体質性黄疸合併慢性C型肝炎症例でも3剤併用後のTBの上昇は一過性で禁忌ではなく、DBや肝逸脱酵素の上昇などを伴わない限り中止の必要性はないと考えられた。(著者抄録)

Background and Aim Patients who undergo gastrointestinal endoscopy often require sedatives such as midazolam and the more recently developed alpha-2 agonist, dexmedetomidine. To assess the efficacy and safety of dexmedetomidine sedation for gastrointestinal endoscopy, we conducted a systematic review and meta-analysis of randomized controlled trials comparing dexmedetomidine with midazolam. Methods We searched PubMed, the Cochrane library, and the Igaku-chuo-zasshi database in order to identify randomized trials eligible for inclusion in our meta-analysis. Data from the eligible studies were combined to calculate pooled odds ratios (OR) or weighted mean differences (WMD). Results We identified nine randomized trials from the database search. Compared to that of midazolam, the pooled OR for restlessness of dexmedetomidine was 0.078 (95% confidence interval [CI]: 0.013-0.453, P < 0.0001), and there was no significant heterogeneity among the trial results. Dexmedetomidine significantly increased Ramsay sedation score compared with midazolam (WMD: 0.401, 95% CI: 0.110-0.692, P = 0.0069), without significant heterogeneity. Compared with midazolam, the pooled OR for hypoxia, hypotension, and bradycardia with dexmedetomidine sedation were 0.454 (95% CI: 0.098-2.11), 1.370 (95% CI: 0.516-3.637), and 2.575 (95% CI: 0.978-6.785), respectively, with no significant differences detected between the groups. Conclusion This meta-analysis shows that dexmedetomidine is a safe and effective sedative agent for gastrointestinal endoscopy, especially endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection.