2006103643649 bezafibrate 1 58 IgG4 ERCPMRCP band-like stricture beaded appearancepsc bezafibrate 400mgday ALPGGT PSC bezafibrate bezafibrate PSC UDCA 2003 388 UDCA 304 78 120 31 bezafibrate UDCA PSC bezafibrate I 58 2003 8 20 AST 94IULALT 97IULGGT 441IUL 153.4cm 58kg 36.1 11468mmHg 72 1 2 3 37
644 103 6 Table1. 初診時検査成績 Hematology BUN 14mg/dL WBC 9160/μL Cr 0.6mg/dL Neut 71.7% Na 142mEq/L Lym 20.3% K 4.2mEq/L Mono 7.8% Cl 104mEq/L Eos 0.1% Fe 144μg/dL Baso 0.1% Ferritin 170ng/mL RBC 414 10 4 /μl Cu 186μg/dL Hb 13.5g/dL セルロプラスミン 42mg/dL Plt 28.4 10 4 /μl ヒアルロン酸 192ng/mL CRP 0.1mg/dL ESR 43/hr Serology Coagulation HBsAg PT 89.7% HCVAb 総胆汁酸 10.1μmol/L IgG 1880mg/dL IgG4 20.2mg/dL Bloodchemistry IgA 334mg/dL TP 8.0g/dL IgM 133mg/dL γ-glob 21.5% ANA Alb 4.3g/dL AMA T.Bil 0.7mg/dL ALKM-1 AST 59IU/L ASMA ALT 93IU/L RAPA LDH 191IU/L ASS-A ALP 530IU/L ASS-B GGT 493IU/L MPO-ANCA ChE 216IU/L TTT 15.2KU AFP 6.5ng/mL ZTT 18.3KU CEA 2.4ng/mL T.Cho 215mg/dL CA19-9 34.8U/mL Table 1 TTTZTTγ- IgG IgG IgG4 MPO-ANCA AFP CEACA19-9 Figure 1 CT Figure 2 ERCPFigure 3 bandlike stricturebeaded appearance MRCPERCP Figure 4 I Varter 38
18 6 645 Figure1. 腹部超音波検査 a: 上部総胆管の拡張 ( 胆管径 12mm) を認めた ( 矢印 ). b: 下部総胆管の狭窄と壁の軽度肥厚を認めた ( 矢印 ). Figure2. 腹部 CT 検査 a: 肝内胆管に変化はみられず腫瘍性病変も認められなかった. b: 胆嚢壁の軽度肥厚を認めた. Figure 5ERCPMRCP IgG4 AIP IgG4 PSC 2003 11 11 T-Chol 271mgdL bezafibrate 400mgday 1 ALP 2004 5 8 333IUL ASTALT GGTT-Chol 3 1 1 MRCP II PSC PSC AIP IgG4 IgG4 IgG4 39
646 103 6 Figure3. ERCP a: 肝内および肝外胆管壁は不整像を呈し不規則な狭小化を認めた. 肝外胆管は帯状に狭窄し (band-likestricture)( 矢印 ) 数珠様変化 (beadedappearance) も認められた. b: 膵管には不整は認められなかった. Figure4. 肝生検組織像 (HE 染色 200): 門脈域の細胆管は軽度増生しリンパ球, 組織球を中心とする炎症細胞の浸潤を認めた. 肝細胞の破壊は軽度で類洞内にリンパ球の浸潤を認めた. PSC IgG4 20.2 mgdl ERCP PSC PSC azathioprinecyclosporinmethotrexatetacrolimus Dpenicillamine colchicine UDCA UDCA PSC PBC UDCA PSC Mayo PSC-UDCA study group UDCA 1 2 ALPALTbilirubinalbumin 6 UDCA azathioprine budesonide Kita Kurihara bezafibrate PBC 40
18 6 647 Figure5. 臨床経過 2003 年 11 月 11 日,T-Chol 値が 271mg/dL と上昇したため bezafibrate400mg/day 経口単独投与を開始した. 開始 1 カ月目より脂質系の低下とともにトランスアミナーゼ, 胆道系酵素の低下を認めた.ALP は 5 月 8 日に 333IU/L と正常値まで低下したが AST,ALT,GGT,T-Chol は正常化には至らず 3 カ月目頃より横ばい状態となった. その後 1 年以上経過しているがトランスアミナーゼ, 胆道系酵素に再増悪は認めていない. UDCA Bezafibrate bezafibrate multidrug registant gene3mdr3mdr3-pglycoprotein MDR3-P-glycoprotein phospholipid phospholipid cytoprotective bezafibrate peroxisome proliferator activated receptor αpparα PPARα NF-κB IL-6 COX-2 β leukotriene B4 ApoA-II ICAMVCAM-1 bezafibrate ASTALTALP GGTT-CholTG 1 3 1 41
648 103 6 Bezafibrate PSC bezafibrate 1Martins E, Graham AK, Chapman RW, et al : Elevation of gamma delta T lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver disease. Hepatology 23 ; 988993 : 1996 2 Takikawa H, Takamori Y, Tanaka A, et al : Analysis of 388 cases of primary sclerosing cholangitis in Japan Presence of a subgroup without pancreatic involvement in older patients. Hepatol Res 29 ; 153159 : 2004 3Kita R, Kita-Sasai Y, Hanaoka I, et al : Benefical effect of bezafibrate on primary sclerosing cholangitis (three case reports). Am J Gastroenterol 97 ; 18491851 : 2002 4Kurihara T, Maeda A, Shigemoto M, et al : Efficacy of bezafibrate in a patient with primary sclerosing cholangitis. J Gastroenterol 38 ; 300 301 : 2003 5 PSC 49 ; 193198 : 2004 6Hamano H, Kawa S, Horiuchi A, et al : High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344 ; 732738 : 2001 7 2002 17 ; 585587 : 2002 8 IgG4- associated sclerosing cholangitis 3 101suppl; A373 : 2004 9Chapman RW : The management of primary sclerosing cholangitis. Curr Gastroenterol Rep 5 ; 9 17 : 2003 10Lindor KD : Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis- Ursodeoxycholic Acid Study Group. N Engl J Med 336 ; 691695 : 1997 11Poupon RE, Balkau B, Eschwege E, et al : A multicenter controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 324 ; 15481554 : 1991 12Paumgartner G, Beuers U : Ursodeoxycholic acid in cholestatic liver disease : mechanisms of action and therapeutic use revisited. Hepatology 36 ; 525531 : 2002 13Iwasaki S, Tsuda K, Ueta H, et al : Bezafibrate may have a beneficial effect in precirrhotic primary biliary cirrhosis. Hepatol Res 16 ; 12 18 : 1999 14 Bezafibrate 43 ; 10571063 : 2001 15Staels B, Koenig W, Habib A, et al : Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393 ; 790793 : 1998 16Devchand PR, Keller H, Peters JM, et al : The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384 ; 3943 : 1996 17Calabresi L, Franceschini G, Sirtori CR, et al : Inhibition of VCAM-1 expression in endothelial cells by reconstituted high density lipoproteins. BBRC 238 ; 6165 : 1997 17 4 25 17 11 25 42
18 6 649 Bezafibrate alone is an effective first-line therapy for primary sclerosing cholangitis : A case report Kazuhisa GONDOH, Tetsujiro ONO, Kenji MIYAKODA, Michita MUKASA, Atsushi SO, Kenichiro IMAMURA and Michio SATA 1 Gondoh Medical Clinic 2 Internal Medicine of Fukuoka Prefectural Yanagawa Hospital 3 The Second Department of Internal Medicine, Kurume University School of Medicine The patient was a 58-year-old female. Though she had been in good health, increased hepatobiliary enzymes were detected in a health examination. She visited our hospital for close examination. The serum IgG4 level was normal, but ERCP and MRCP showed band-like stricture and beaded appearance of the bile ducts. A diagnosis of primary sclerosing cholangitis (PSC) was made. Since hyperlipidemia was also observed, oral administration of bezafibrate (400mgday) alone was performed as the initial treatment, and transaminase, ALP, and GGT rapidly decreased. These results suggested that the initial administration of bezafibrate alone is effective against PSC. 43