今日の臨床サポート

原発性硬化性胆管炎

著者: 中沢貴宏 名古屋市立大学 消化器・代謝内科学

監修: 田妻進 広島大学病院 総合内科・総合診療科

著者校正/監修レビュー済:2021/11/02
参考ガイドライン:
  1. 日本胆道学会:Clinical guidelines for primary sclerosing cholangitis 2017.J Gastroenterol (2018) 53:1006–1034
  1. British Society of Gastroenterology(BSG):British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019;68:1356–1378
  1. 日本胆道学会:Clinical practice guidelines for IgG4-related sclerosing cholangitis. J Hepatobiliary Pancreat Sci (2019) 26:9–42
  1. 日本胆道学会:Clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020. J Hepatobiliary Pancreat Sci. 2021;00:1–8.
患者向け説明資料

概要・推奨   

  1. PSCとIgG4関連硬化性胆管炎との鑑別診断のためにERCPなどの直接胆管造影を行うことが推奨される(推奨度2、OJ)。
  1. PSCの診断のためにMRCPを行うことは強く推奨される(推奨度1、RSJG)。
  1. PSCとIgG4関連硬化性胆管炎とを鑑別診断するために血清IgG4を測定することは強く推奨される(推奨度1、OJG)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中沢貴宏 : 未申告[2021年]
監修:田妻進 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、以下について加筆修正を行った。
  1. PSCは欧米の症例数が多数あるため、海外(英国)のガイドラインの内容も一部紹介した。
  1. 鑑別診断として重要なIgG4関連硬化性胆管炎のガイドライン、診断基準が改定され内容を一部紹介した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 原発性硬化性胆管炎(primary sclerosing cholangitis、PSC)は原因不明の慢性胆汁うっ滞性の肝疾患で、肝内外胆管のびまん性の炎症と線維化により徐々に胆管狭窄を来し、病態が進行すると胆汁性肝硬変となり、門脈圧亢進や肝不全に至る疾患である[1][2]
  1. 原発性硬化性胆管炎(PSC)の診断基準[3]<図表>
  1. 大項目
  1. A. 原発性硬化性胆管炎に特徴的な胆管像の所見を認める。<図表><図表><図表><図表><図表>
  1. B. ALPの上昇アルゴリズム
  1. 小項目
  1. a. 炎症性腸疾患の合併
  1. b. 肝組織像
  1. 線維性の胆管炎
  1. 除外項目
  1. 二次性硬化性胆管炎を除外する<図表>
  1. 注意点:
  1. 若年者では自己免疫性肝炎(AIH)とのオーバーラップを認めることがあり、肝生検像や自己抗体から判断する。
  1. 原発性硬化性胆管炎は、指定難病であり、①有症状の患者(黄疸、皮膚掻痒、胆管炎、腹水、消化管出血、肝性脳症、胆管癌など)、または②ALPが施設基準上限の2倍以上の患者などは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される。(原発性硬化性胆管炎
  1. 難病法に基づく医療費助成制度
問診・診察のポイント  
  1. 2015年に行われたPSC患者435名の全国調査[4]によると、男女比は263:172と男性(60%)にやや多く、年齢分布は20歳代と60歳代に2つのピークがみられた。また、診断時の初発症状は黄疸が19%で、無症状な症例が62%を占めた。潰瘍性大腸炎などの炎症性腸疾患の合併を40%に認めた。したがって、上記のことを念頭に置きながら、以下の項目に注意して問診と診察を行う必要がある。
  1. 炎症性腸疾患の合併の有無

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文献 

著者: Takahiro Nakazawa, Kenji Notohara, Susumu Tazuma, Atsushi Tanaka, Hiroyuki Isayama, Toshio Tsuyuguchi, Toshiyuki Mori, Hajime Takikawa
雑誌名: J Gastroenterol. 2017 Jul;52(7):838-844. doi: 10.1007/s00535-016-1286-x. Epub 2016 Dec 5.
Abstract/Text BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown cause that is characterized pathologically by an inflammatory and fibrotic process centered on the epithelium, leading to diffuse biliary stenosis and increased wall thickness throughout the intra- and extra-hepatic biliary trees. A nationwide survey in Japan revealed several differences in the clinical aspects of PSC between Japan and Western countries. PSC was recently designated an intractable hepatobiliary disease in Japan. The aim of this study was to establish Japanese diagnostic criteria for PSC according to the current Japanese conditions.
METHODS: The Intractable Hepato-Biliary Diseases Study Group in Japan of the Committee of Research on Measures for Intractable Diseases established a working group consisting of researchers specializing in PSC and proposed the 2016 Japanese diagnostic criteria for PSC.
RESULTS: The diagnostic criteria consisted of the major and minor items. Major items are directly related to bile duct changes based on biliary tract imaging and an increased alkaline phosphatase level. Minor items consist of an association with inflammatory bowel disease and liver histology.
CONCLUSION: The diagnostic criteria for PSC are useful for general physicians in practice.

PMID 27921168  J Gastroenterol. 2017 Jul;52(7):838-844. doi: 10.1007/s・・・
著者: Atsushi Tanaka, Susumu Tazuma, Takahiro Nakazawa, Hiroyuki Isayama, Toshio Tsuyuguchi, Kazuo Inui, Hajime Takikawa
雑誌名: J Hepatobiliary Pancreat Sci. 2017 Apr;24(4):217-225. doi: 10.1002/jhbp.432. Epub 2017 Mar 4.
Abstract/Text BACKGROUND: Several studies have demonstrated that elevated serum IgG4 levels are associated with poor outcomes of primary sclerosing cholangitis (PSC), but the impact of serum IgG4 levels on PSC remains controversial. In this study, we aimed to determine prognostic factors of patients with PSC and to investigate the association between serum IgG4 levels and the clinical features and prognosis of PSC in a Japanese cohort.
METHODS: We retrospectively analyzed follow-up data for 435 patients with PSC (UMIN000018438). Patients with distinct etiologies of sclerosing cholangitis including IgG4-related sclerosing cholangitis (IgG4-SC) were excluded from this study.
RESULTS: Serum IgG4 levels were tested at the time of diagnosis in 216 of 435 patients with PSC, and were elevated in 27 patients (>134 mg/dl, 12.5%). Clinical features at diagnosis were comparable between patients with normal and elevated serum IgG4 levels, with the exception of serum albumin. The overall and liver-transplantation free survival rate was comparable between the groups. Multivariate analysis indicated that age, albumin, and bilirubin, but not IgG4, at the time of diagnosis affected PSC prognosis.
CONCLUSIONS: The current study showed that serum IgG4 levels at diagnosis do not affect PSC prognosis in a Japanese cohort that excluded patients with IgG4-SC.

© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
PMID 28103424  J Hepatobiliary Pancreat Sci. 2017 Apr;24(4):217-225. d・・・
著者: Takahiro Nakazawa, Hirotaka Ohara, Hitoshi Sano, Shigeru Aoki, Shinya Kobayashi, Tetsu Okamoto, Hideto Imai, Tomoyuki Nomura, Takashi Joh, Makoto Itoh
雑誌名: Gastrointest Endosc. 2004 Dec;60(6):937-44.
Abstract/Text BACKGROUND: Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis.
METHODS: Cholangiograms from patients with primary sclerosing cholangitis (n = 29) and sclerosing cholangitis with autoimmune pancreatitis (n = 26) were studied with regard to length and region of stricture formation, and other characteristic findings.
RESULTS: Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis.
CONCLUSIONS: Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

PMID 15605009  Gastrointest Endosc. 2004 Dec;60(6):937-44.
著者: Hirotaka Ohara, Kazuichi Okazaki, Hirohito Tsubouchi, Kazuo Inui, Shigeyuki Kawa, Terumi Kamisawa, Susumu Tazuma, Kazushige Uchida, Kenji Hirano, Hitoshi Yoshida, Takayoshi Nishino, Shigeru B H Ko, Nobumasa Mizuno, Hideaki Hamano, Atsushi Kanno, Kenji Notohara, Osamu Hasebe, Takahiro Nakazawa, Yasuni Nakanuma, Hajime Takikawa, Research Committee of IgG4-related Diseases, Research Committee of Intractable Diseases of Liver and Biliary Tract, Ministry of Health, Labor and Welfare, Japan, Japan Biliary Association
雑誌名: J Hepatobiliary Pancreat Sci. 2012 Sep;19(5):536-42. doi: 10.1007/s00534-012-0521-y.
Abstract/Text BACKGROUND: IgG4-sclerosing cholangitis (IgG4-SC) patients have an increased level of serum IgG4, dense infiltration of IgG4-positive plasma cells with extensive fibrosis in the bile duct wall, and a good response to steroid therapy. However, it is not easy to distinguish IgG4-SC from primary sclerosing cholangitis, pancreatic cancer, and cholangiocarcinoma on the basis of cholangiographic findings alone because various cholangiographic features of IgG4-SC are similar to those of the above progressive or malignant diseases.
METHODS: The Research Committee of IgG4-related Diseases and the Research Committee of Intractable Diseases of Liver and Biliary Tract in association with the Ministry of Health, Labor and Welfare, Japan and the Japan Biliary Association have set up a working group consisting of researchers specializing in IgG4-SC, and established the new clinical diagnostic criteria of IgG4-SC 2012.
RESULTS: The diagnosis of IgG4-SC is based on the combination of the following 4 criteria: (1) characteristic biliary imaging findings, (2) elevation of serum IgG4 concentrations, (3) the coexistence of IgG4-related diseases except those of the biliary tract, and (4) characteristic histopathological features. Furthermore, the effectiveness of steroid therapy is an optional extra diagnostic criterion to confirm accurate diagnosis of IgG4-SC.
CONCLUSION: These diagnostic criteria for IgG4-SC are useful in practice for general physicians and other nonspecialists.

PMID 22717980  J Hepatobiliary Pancreat Sci. 2012 Sep;19(5):536-42. do・・・
著者: H Hamano, S Kawa, A Horiuchi, H Unno, N Furuya, T Akamatsu, M Fukushima, T Nikaido, K Nakayama, N Usuda, K Kiyosawa
雑誌名: N Engl J Med. 2001 Mar 8;344(10):732-8. doi: 10.1056/NEJM200103083441005.
Abstract/Text BACKGROUND: Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract.
METHODS: We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjögren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor.
RESULTS: The median serum IgG4 concentration in the patients with sclerosing pancreatitis was 663 mg per deciliter (5th and 95th percentiles, 136 and 1150), as compared with 51 mg per deciliter (5th and 95th percentiles, 15 and 128) in normal subjects (P<0.001). The serum IgG4 concentrations in the other groups of patients were similar to those in the normal subjects. In patients with sclerosing pancreatitis, serum concentrations of immune complexes and the IgG4 subclass of immune complexes were significantly higher before glucocorticoid therapy than after four weeks of such therapy. Glucocorticoid therapy induced clinical remissions and significantly decreased serum concentrations of IgG4, immune complexes, and the IgG4 subclass of immune complexes.
CONCLUSIONS: Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.

PMID 11236777  N Engl J Med. 2001 Mar 8;344(10):732-8. doi: 10.1056/NE・・・
著者: Takahiro Nakazawa, Hirotaka Ohara, Hitoshi Sano, Tomoaki Ando, Shigeru Aoki, Shinya Kobayashi, Tetsu Okamoto, Tomoyuki Nomura, Takashi Joh, Makoto Itoh
雑誌名: Pancreas. 2005 Jan;30(1):20-5.
Abstract/Text OBJECTIVES: Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing cholangitis (PSC) with regard to cholangiographic findings, but only the former responds well to steroid therapy. This report concentrates on the clinical differences between these diseases.
METHODS: The presenting complaint or abnormality, associated disease, cholangiographic findings, pancreatic changes, treatment, and clinical course were studied for several cases of PSC (n = 27) and SC with AIP (n = 20).
RESULTS: SC with AIP as a diagnosis occurs abruptly with obstructive jaundice compared with PSC where diagnosis is often based on findings of asymptomatic liver test abnormalities. In addition, inflammatory bowel disease is only associated with PSC. The most prominent features of cholangiograms for the SC with AIP cases were stenosis of the lower common bile duct. However, sclerosing changes in the intra- and extrahepatic bile ducts or hilar hepatic region were observed for half of the cases. Only PSC showed stage III or IV liver biopsy findings. IgG4 was significantly higher in SC with AIP.
CONCLUSIONS: SC with AIP and PSC are different clinical entities.

PMID 15632695  Pancreas. 2005 Jan;30(1):20-5.
著者: Takahiro Nakazawa, Itaru Naitoh, Kazuki Hayashi, Fumihiro Okumura, Katsuyuki Miyabe, Michihiro Yoshida, Hiroaki Yamashita, Hirotaka Ohara, Takashi Joh
雑誌名: J Gastroenterol. 2012 Jan;47(1):79-87. doi: 10.1007/s00535-011-0465-z. Epub 2011 Sep 23.
Abstract/Text BACKGROUND: IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria for IgG4-SC based on cholangiographic classification by comparison with several diagnostic modalities.
METHODS: We classified 62 IgG4-SC patients into three groups on the basis of cholangiographic findings to allow differentiation from PCa, PSC, and CC: Group A IgG4-SC showed features similar to PCa (Type 1, n = 32), Group B showed similarity to PSC (Type 2, n = 15), and Group C showed similarity to CC (Type 3, 4, n = 15). Thirty-five patients with PCa, 40 with PSC, and 32 CC were enrolled as controls. We retrospectively compared the clinical, imaging, serological, and histopathological features and involvement of other organs between Group A and PCa, Group B and PSC, and Group C and CC.
RESULTS: Association with autoimmune pancreatitis (AIP) (P < 0.001) and involvements with other organs (specificity 100%) were common useful diagnostic parameters in all three IgG4-SC groups. A high serum IgG4 level was a useful parameter in Groups A and B (P < 0.001). Discriminant analysis of cholangiograms (P < 0.001), liver biopsy (specificity 100%), and exclusion of inflammatory bowel disease (specificity 100%) were useful parameters in Group B. Intraductal ultrasonography findings (P < 0.001) and exclusion of malignancy by bile duct biopsy (specificity 100%) were useful parameters in Group C. We established diagnostic criteria for IgG4-SC (sensitivity 100%, specificity 96.3%) by incorporating parameters that showed P < 0.001 or 100% specificity.
CONCLUSIONS: Diagnostic criteria for IgG4-SC based on cholangiographic classification are useful for distinguishing it from PCa, PSC, and CC.

PMID 21947649  J Gastroenterol. 2012 Jan;47(1):79-87. doi: 10.1007/s00・・・
著者: Flavia D Mendes, Roberta Jorgensen, Jill Keach, Jerry A Katzmann, Thomas Smyrk, Jessica Donlinger, Suresh Chari, Keith D Lindor
雑誌名: Am J Gastroenterol. 2006 Sep;101(9):2070-5. doi: 10.1111/j.1572-0241.2006.00772.x. Epub 2006 Jul 27.
Abstract/Text OBJECTIVES: Biliary strictures, similar to primary sclerosing cholangitis (PSC), have been reported in patients with autoimmune pancreatitis, which is characterized by elevated serum IgG4 levels and responsiveness to corticosteroids. We sought to determine the frequency of elevated IgG4 in patients with PSC and to clinically compare PSC patients with elevated and normal IgG4 levels.
METHODS: We measured serum IgG4 in 127 patients with PSC and 87 patients with primary biliary cirrhosis, as disease controls. Demographic, clinical, and laboratory characteristics were compared between the PSC groups with normal and elevated IgG4 (>140 mg/dL).
RESULTS: Elevated IgG4 was found in 12 PSC patients (9%) versus one PBC patient (1.1%) (p= 0.017). Patients with elevated IgG4 had higher total bilirubin (p= 0.009), alkaline phosphatase (p= 0.01), and PSC Mayo risk score (p= 0.038), and lower frequency of IBD (p < 0.0001). Importantly, the time to liver transplantation was shorter in patients with elevated IgG4 (1.7 vs 6.5 yr, p= 0.0009). The type of biliary involvement (intrahepatic, extrahepatic, or both) and pancreatic involvement were similar in both groups.
CONCLUSIONS: A small proportion of PSC patients had elevated serum IgG4. In these patients parameters of liver disease severity were more pronounced and time to liver transplantation was shorter, suggesting a more severe disease course. It is possible that this subset of patients behaves similarly to autoimmune pancreatitis patients with biliary strictures, and could potentially respond to corticosteroids. Testing PSC patients for IgG4 and treating those with elevated levels with corticosteroids in clinical trials should be considered.

PMID 16879434  Am J Gastroenterol. 2006 Sep;101(9):2070-5. doi: 10.111・・・
著者: Masanori Koyabu, Kazushige Uchida, Norimasa Fukata, Takeo Kusuda, Tsukasa Ikeura, Yutaku Sakaguchi, Katsunori Yoshida, Masaaki Shimatani, Toshiro Fukui, Mitsunobu Matsushita, Yoshiko Uemura, Masaki Kaibori, Makoto Takaoka, Akiyoshi Nishio, Kazuichi Okazaki
雑誌名: J Gastroenterol. 2010;45(1):122-9. doi: 10.1007/s00535-009-0130-y. Epub 2009 Sep 18.
Abstract/Text Immunoglobin G4-related sclerosing cholangitis (IgG4-SC) is recognized as one of the systemic sclerosing diseases characterized by abundant IgG4-positive plasma cells with effective steroid therapy. On the other hand, primary sclerosing cholangitis (PSC), recognized as a sclerosing cholangitis of unknown origin without steroid efficacy, has been often clinically confused with IgG4-SC. To date, the prognosis of IgG4-SC is unclear, while the prognosis of PSC is well known to be poor. Therefore, it is clinically very important to be able to distinguish IgG4-SC from PSC. However, at the present time it still remains unclear whether PSC may sometimes be misdiagnosed as IgG4-SC or not. Herein, we report three rare cases of PSC with elevated serum IgG4 levels and/or an infiltration of abundant IgG4-positive plasma cells in the liver: a young male with ulcerative colitis (UC), and elderly female and a young female, each with elevated serum IgG4 levels. The first two patients showed infiltration of abundant IgG4-positive plasma cells in the portal area of the liver without response to steroid therapy. From our experiences, we emphasize that some patients with PSC, who do not respond to steroid therapy, show elevated serum IgG4 levels and/or infiltration of abundant IgG4-positive plasma cells, although the mechanism still remains unclear.

PMID 19760481  J Gastroenterol. 2010;45(1):122-9. doi: 10.1007/s00535-・・・
著者: Hiroyuki Isayama, Susumu Tazuma, Norihiro Kokudo, Atsushi Tanaka, Toshio Tsuyuguchi, Takahiro Nakazawa, Kenji Notohara, Suguru Mizuno, Nobuhisa Akamatsu, Masahiro Serikawa, Itaru Naitoh, Yoshiki Hirooka, Toshifumi Wakai, Takao Itoi, Tomoki Ebata, Shinji Okaniwa, Terumi Kamisawa, Hiroki Kawashima, Atsushi Kanno, Keiichi Kubota, Masami Tabata, Michiaki Unno, Hajime Takikawa, PSC guideline committee Members: Ministry of Health, Labour and Welfare (Japan) Research Project, The Intractable Hepatobiliary Disease Study Group
雑誌名: J Gastroenterol. 2018 Sep;53(9):1006-1034. doi: 10.1007/s00535-018-1484-9. Epub 2018 Jun 27.
Abstract/Text BACKGROUND: Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC.
METHODS: We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA.
RESULTS: We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart.
CONCLUSIONS: We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.

PMID 29951926  J Gastroenterol. 2018 Sep;53(9):1006-1034. doi: 10.1007・・・
著者: Maneesh Dave, B Joseph Elmunzer, Ben A Dwamena, Peter D R Higgins
雑誌名: Radiology. 2010 Aug;256(2):387-96. doi: 10.1148/radiol.10091953.
Abstract/Text PURPOSE: To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) for detection of primary sclerosing cholangitis (PSC) in patients with biochemical cholestasis.
MATERIALS AND METHODS: Two reviewers searched MEDLINE, EMBASE, and other electronic databases to identify prospective studies in which MRCP was evaluated and compared with endoscopic retrograde cholangiopancreatography (ERCP), clinical examination, and/or histologic analysis for diagnosis of PSC in cholestasis and control cases. Main study inclusion criteria were (a) use of ERCP or percutaneous transhepatic cholangiography (PTC) as part of the reference standard for the diagnosis of PSC, (b) inclusion of patients with hepatobiliary disease other than PSC (ie, nonhealthy control subjects), (c) blinding of MRCP image readers to reference-standard results, (d) prospective study with ERCP or MRCP performed after subject recruitment into the study, and (e) inclusion of raw data (for true-positive, false-positive, true-negative, and false-negative results) that could be found or calculated from the original study data. Major exclusion criteria were duplicate article (on a primary study) that contained all or some of the original study data and inclusion of fewer than 10 patients with PSC. Methodologic quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies tool. Bivariate random-effects meta-analytic methods were used to estimate summary, sensitivity, specificity, and receiver operating characteristic (ROC) curves.
RESULTS: Six manuscripts with 456 subjects (with 623 independent readings)--185 with PSC--met the study inclusion criteria. The summary area under the ROC curve was 0.91. High heterogeneity (inconsistency index, 78%) was found but became moderate (inconsistency index, 36%) with the exclusion of one study in which the diagnostic threshold was set for high sensitivity. There was no evidence of publication bias (P = .27, bias coefficient analysis). Sensitivity and specificity of MRCP for PSC detection across all studies were 0.86 and 0.94, respectively. Positive and negative likelihood ratios with MRCP were 15.3 and 0.15, respectively. In patients with high pretest probabilities, MRCP enabled confirmation of PSC; in patients with low pretest probabilities, MRCP enabled exclusion of PSC. Worst-case-scenario (pretest probability, 50%) posttest probabilities were 94% and 13% for positive and negative MRCP results, respectively.
CONCLUSION: MRCP has high sensitivity and very high specificity for diagnosis of PSC. In many cases of suspected PSC, MRCP is sufficient for diagnosis, and, thus, the risks associated with ERCP can be avoided.

PMID 20656832  Radiology. 2010 Aug;256(2):387-96. doi: 10.1148/radiol.・・・
著者: C Weber, R Kuhlencordt, R Grotelueschen, U Wedegaertner, T L Ang, G Adam, N Soehendra, U Seitz
雑誌名: Endoscopy. 2008 Sep;40(9):739-45. doi: 10.1055/s-2008-1077509. Epub 2008 Aug 12.
Abstract/Text BACKGROUND AND STUDY AIMS: Magnetic resonance cholangiopancreatography (MRCP) is a less-invasive alternative to endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of primary sclerosing cholangitis (PSC). This study evaluated the diagnostic accuracy of MRCP in PSC compared with ERCP, and assessed the diagnostic accuracy of different T2w sequences.
PATIENTS AND METHODS: 95 patients (69 PSC, 26 controls) were evaluated using both ERCP and MRCP. Exclusion criteria included secondary sclerosing cholangitis and contraindications to MRCP. The diagnosis of PSC was confirmed in 69 patients based on ERCP as the reference gold standard. MRCP was performed using a 1.5 Tesla MR unit, using breath hold, coronal and transverse half-Fourier acquisition single-shot turbo spin-echo (HASTE), coronal-oblique, fat-suppressed half-Fourier rapid acquisition with relaxation enhancement (RARE), and coronal-oblique, fat-suppressed, multisection, thin-section HASTE (TS-HASTE) sequences. The MRCP morphological criteria of PSC were evaluated and compared with ERCP.
RESULTS: The sensitivity, specificity, and diagnostic accuracy were 86%, 77%, and 83%, respectively, using the MRCP-RARE sequence, and increased further to 93%, 77%, and 88%, respectively, by the inclusion of follow-up MRCP in 52 patients, performed at 6-12-month intervals. HASTE and TS-HASTE sequences showed significantly lower diagnostic accuracy but provided additional morphologic information.
CONCLUSIONS: MRCP can diagnose PSC but has difficulties in early PSC and in cirrhosis, and in the differentiation of cholangiocarcinoma, Caroli's disease, and secondary sclerosing cholangitis. A positive MRCP would negate some diagnostic ERCP studies but a negative MRCP would not obviate the need for ERCP.

PMID 18698533  Endoscopy. 2008 Sep;40(9):739-45. doi: 10.1055/s-2008-1・・・
著者: Konstantinos N Lazaridis, Gregory J Gores
雑誌名: Semin Liver Dis. 2006 Feb;26(1):42-51. doi: 10.1055/s-2006-933562.
Abstract/Text Primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by fibrosing inflammatory damage of the biliary tree, is a risk factor for cholangiocarcinoma (CCA). Indeed, the prevalence of CCA in patients with PSC ranges from 7 to 13%. The major challenges of CCA in PSC patients relate to lack of methods for early diagnosis and the absence of effective treatment. Early diagnosis of CCA in PSC is delayed because its clinical presentation can mimic benign dominant biliary strictures. Moreover, biliary and serum tests to diagnose development of CCA in PSC are limiting, although the use of advanced cytologic techniques for aneuploidy and chromosomal aberrations are promising in this regard. As a result, current therapies do not extend survival with the exception of protocol liver transplantation available to a selected group of patients. Future studies should emphasize deciphering the sequence of events that transform the inflammatory changes of the biliary tree to cancer. Only then will chemoprevention, early diagnosis, and therapy of CCA in patients with PSC improve.

PMID 16496232  Semin Liver Dis. 2006 Feb;26(1):42-51. doi: 10.1055/s-2・・・
著者: Atsushi Tanaka, Yoriyuki Takamori, Gotaro Toda, Saburo Ohnishi, Hajime Takikawa
雑誌名: Liver Int. 2008 Aug;28(7):983-9. doi: 10.1111/j.1478-3231.2008.01726.x. Epub 2008 Apr 7.
Abstract/Text OBJECTIVES: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients.
METHODS: Questionnaires were sent to gastroenterologists in Japan, and 391 patients with PSC were registered and enrolled in the current study. The median follow-up was 5.3 years (range 0.1-20.8 years). The cumulative incidence for survival was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox-proportional hazards regression model for determining prognostic variables.
RESULTS: The estimated median survival of all patients was 13.1 years, with a 5-year survival rate of 74.5%. Thirty-eight patients (9.7%) who underwent liver transplantation (LT) had a 5-year survival rate of 92.0%. Both univariate and multivariate analysis demonstrated that younger age [below 49 years old; odds ratio (OR)=1.76, 1.12-2.76, P=0.0136] and lower total bilirubin (below 3.0 mg/dl; OR=2.50, 1.60-3.89, PCONCLUSIONS: Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.

PMID 18397233  Liver Int. 2008 Aug;28(7):983-9. doi: 10.1111/j.1478-32・・・
著者: Karouk Said, Hans Glaumann, Annika Bergquist
雑誌名: J Hepatol. 2008 Apr;48(4):598-605. doi: 10.1016/j.jhep.2007.11.019. Epub 2008 Jan 2.
Abstract/Text BACKGROUND/AIMS: Gallbladder abnormalities may be part of the spectrum in primary sclerosing cholangitis (PSC). The aim of the present study was to evaluate the occurrence and prognostic importance of gallbladder abnormalities in patients with PSC.
METHODS: Presence of gallbladder abnormalities was assessed in 286 patients with PSC treated at the Liver Unit, Karolinska University Hospital, Huddinge, between 1970 and 2005.
RESULTS: One or more gallbladder abnormalities were found in 41% of the patients. Gallstones were found in 25% and cholecystitis in 25%. Cholecystitis among patients with extrahepatic involvement of PSC (30% (65/214)) was significantly higher than among those with intrahepatic involvement (9% (6/70)) (P<0.0001). A gallbladder mass lesion with a mean size of 21 (+/-9) mm (S.D.) was found in 18 (6%) patients, in 56% (10/18) of whom it constituted gallbladder carcinoma. In 9 patients without a gallbladder mass lesion, histological re-evaluation disclosed epithelial dysplasia of the gallbladder.
CONCLUSIONS: Gallbladder disease is common in patients with PSC. Dysplasia and carcinoma are commonly found in gallbladder epithelium, suggesting that regular examination of the gallbladder in PSC patients could be of value for early detection of a gallbladder mass lesion. Cholecystectomy is recommended when such a lesion is detected, regardless of its size.

PMID 18222013  J Hepatol. 2008 Apr;48(4):598-605. doi: 10.1016/j.jhep.・・・
著者: Hitoshi Sano, Takahiro Nakazawa, Tomoaki Ando, Kazuki Hayashi, Itaru Naitoh, Fumihiro Okumura, Katsuyuki Miyabe, Michihiro Yoshida, Satoru Takahashi, Hirotaka Ohara, Takashi Joh
雑誌名: J Hepatobiliary Pancreat Sci. 2011 Mar;18(2):154-61. doi: 10.1007/s00534-010-0319-8.
Abstract/Text PURPOSE: Only a few studies have documented the characteristics of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC). We aimed to clarify the clinical and histopathological characteristics of IBD associated with PSC (PSC-IBD).
METHODS: Twenty-nine patients with PSC and 60 patients with ulcerative colitis (UC) but without complicating PSC were enrolled in this study. First, the age and sex distribution, affected area, clinical course, number of recurrent attacks, and severity of UC were investigated. Then, mucosal specimens obtained from the right side (cecum and ascending colon), transverse colon, and the left side (descending colon, sigmoid colon, and rectum) during colonoscopy were studied for inflammatory cell infiltration, the presence of crypt abscesses, the degree of goblet cell disappearance, and edema.
RESULTS: (1) The incidence of IBD in PSC patients was 68.9% (20/29). There were two peaks in the age distribution of PSC. Male PSC patients demonstrated a first peak and female patients a second peak. Male PSC-IBD patients were in their teens and 20s making the first peak. Female PSC-IBD patients were in their 50s and 60s making the second peak. The PSC-IBD patents were significantly younger than the patients without IBD (33.6 vs. 58.9 years, p < 0.001). (2) PSC-IBD showed a right-sided predominance colonoscopically. (3) None of the patients had a severe clinical course, and a half of them were asymptomatic. (4) Histopathological examination demonstrated severe inflammatory cell infiltration in the cecum and ascending colon, whereas the degree was mild in the rectum/descending colon.
CONCLUSIONS: PSC-IBD shows characteristic clinical, colonoscopic, and histopathological findings.

PMID 20740366  J Hepatobiliary Pancreat Sci. 2011 Mar;18(2):154-61. do・・・
著者: Roy M Soetikno, Otto S Lin, Paul A Heidenreich, Harvey S Young, Michael O Blackstone
雑誌名: Gastrointest Endosc. 2002 Jul;56(1):48-54.
Abstract/Text BACKGROUND: Published data on the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis are conflicting. A meta-analysis was performed to synthesize available publications and to compare the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis.
METHODS: By using MEDLINE and manual search methods, studies were identified that compared the risk of colorectal neoplasia (dysplasia and carcinoma) in patients with ulcerative colitis with and without primary sclerosing cholangitis. In addition, citations were reviewed in relevant articles and proceedings from gastroenterology meetings, and investigators were contacted when data were incomplete. The summary odds ratio (OR) was then calculated for the risk for patients with ulcerative colitis and primary sclerosing cholangitis of having colorectal neoplasia develop compared with that of patients with ulcerative colitis without primary sclerosing cholangitis.
RESULTS: Eleven studies met all eligibility criteria for the meta-analysis. Patients with ulcerative colitis and primary sclerosing cholangitis are at increased risk of colorectal dysplasia and carcinoma compared with patients with ulcerative colitis alone; OR 4.79: 95% CI [3.58, 6.41] with the Mantel-Haenszel method, and OR 5.11: 95% CI [3.15, 8.29] with the Der Simonian and Laird method. This increased risk is present even when the risk of colorectal carcinoma alone is considered; OR 4.09: 95% CI [2.89, 5.76] and OR 4.26: 95% CI [2.80, 6.48] by using, respectively, the Mantel-Haenszel and the Der Simonian and Laird methods.
CONCLUSIONS: Patients with ulcerative colitis and primary sclerosing cholangitis have a significantly higher risk for the development of colorectal neoplasia than patients with ulcerative colitis but not primary sclerosing cholangitis. More intensive colonoscopic surveillance should be considered for patients with ulcerative colitis and primary sclerosing cholangitis.

PMID 12085034  Gastrointest Endosc. 2002 Jul;56(1):48-54.
著者: W R Kim, T M Therneau, R H Wiesner, J J Poterucha, J T Benson, M Malinchoc, N F LaRusso, K D Lindor, E R Dickson
雑誌名: Mayo Clin Proc. 2000 Jul;75(7):688-94. doi: 10.4065/75.7.688.
Abstract/Text OBJECTIVE: To describe a natural history model for primary sclerosing cholangitis (PSC) that is based on routine clinical findings and test results and eliminates the need for liver biopsy.
PATIENTS AND METHODS: Using the Cox proportional hazards analysis, we created a survival model based on 405 patients with PSC from 5 clinical centers. Independent validation of the model was undertaken by applying it to 124 patients who were not included in the model creation.
RESULTS: Based on the multivariate analysis of 405 patients, a risk score was defined by the following formula: R = 0.03 (age [y]) + 0.54 loge (bilirubin [mg/dL]) + 0.54 loge (aspartate aminotransferase [U/L]) + 1.24 (variceal bleeding [0/1]) - 0.84 (albumin [g/dL]). The risk score was used to obtain survival estimates up to 4 years of follow-up. Application of this model to an independent group of 124 patients showed good correlation between estimated and actual survival.
CONCLUSIONS: A new model to estimate patient survival in PSC includes more reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and history of variceal bleeding), has accuracy comparable to previous models, and obviates the need for a liver biopsy.

PMID 10907383  Mayo Clin Proc. 2000 Jul;75(7):688-94. doi: 10.4065/75.・・・
著者: R N Pugh, I M Murray-Lyon, J L Dawson, M C Pietroni, R Williams
雑誌名: Br J Surg. 1973 Aug;60(8):646-9.
Abstract/Text
PMID 4541913  Br J Surg. 1973 Aug;60(8):646-9.
著者: P S Kamath, R H Wiesner, M Malinchoc, W Kremers, T M Therneau, C L Kosberg, G D'Amico, E R Dickson, W R Kim
雑誌名: Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.2001.22172.
Abstract/Text A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as "hospitalized" patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as "historical" patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c-statistic: <.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01-0.03). The MELD scale is a reliable measure of mortality risk in patients with end-stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities.

PMID 11172350  Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.20・・・
著者: Einar Björnsson, Joachim Lindqvist-Ottosson, Mats Asztely, Rolf Olsson
雑誌名: Am J Gastroenterol. 2004 Mar;99(3):502-8. doi: 10.1111/j.1572-0241.2004.04106.x.
Abstract/Text BACKGROUND: Repeat endoscopic dilatations of dominant strictures (DS) have been reported to be of benefit in patients with primary sclerosing cholangitis (PSC). We aimed to determine the prevalence of DS in patients with PSC and the spontaneous course of ALP and bilirubin, up to a year from diagnosis in patients with and without DS.
METHOD: Cholangiographies from 125 patients with PSC were reevaluated. DS was defined as a stenosis < or =1.5 mm in diameter of the common bile duct (CBD) and/or < or = 1.0 mm of right (RHD) or left hepatic duct (LHD).
RESULTS: A dominant stricture in common bile duct and/or right hepatic duct or left hepatic duct was present in 56 out of 125 (45%) patients. Mean values for alkaline phosphatase were 16 and 15.2 microkat/L and bilirubin values were 42 and 35 micromol/L before cholangiography in patients with and without DS, respectively (NS). The change in ALP and bilirubin observed from the precholangiographic value up to 2 and 12 months afterward was not significantly different in those with and without DS.
CONCLUSIONS: Cholestasis in patients with PSC does not seem to be related to the presence of DS. Endoscopic therapy of DS should not be routinely undertaken and randomized studies are needed to clarify its potential benefits.

PMID 15056092  Am J Gastroenterol. 2004 Mar;99(3):502-8. doi: 10.1111/・・・
著者: S A Mitchell, D S Bansi, N Hunt, K Von Bergmann, K A Fleming, R W Chapman
雑誌名: Gastroenterology. 2001 Oct;121(4):900-7.
Abstract/Text BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for the treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) for which it has a positive effect on laboratory values, may delay the development of liver failure and prolong the transplant-free disease period. Standard doses of UDCA (8-15 mg/kg daily) have been shown to be ineffective in the treatment of primary sclerosing cholangitis (PSC). We report on the findings (clinical, biochemical, histological, and cholangiographic) and side effects of a 2-year double-blind placebo-controlled preliminary study of high-dose UDCA in PSC patients.
METHODS: Twenty-six patients with PSC were randomized to high-dose (20 mg/kg daily) UDCA or placebo. Cholangiography and liver biopsy were performed at entry and after 2 years. Symptoms, clinical signs, and liver biochemical tests were recorded at 3 monthly intervals.
RESULTS: High-dose UDCA did not influence symptoms, but there was a significant improvement in liver biochemistry (serum alkaline phosphatase, P = 0.03; gamma-glutamyl transferase, P = 0.01) and a significant reduction in progression in cholangiographic appearances (P = 0.015) and liver fibrosis as assessed by disease staging (P = 0.05). In the treatment group, a significant increase in total bile acids and saturation with UDCA >70% confirmed patient compliance. No significant side effects were reported.
CONCLUSIONS: High-dose UDCA may be of clinical benefit in PSC, but trials with a larger number of participants and of longer duration are required to establish whether the effect of high-dose UDCA on liver biochemistry, histology, and cholangiography in patients with PSC is translated into improved long-term survival.

PMID 11606503  Gastroenterology. 2001 Oct;121(4):900-7.
著者: D M Harnois, P Angulo, R A Jorgensen, N F Larusso, K D Lindor
雑誌名: Am J Gastroenterol. 2001 May;96(5):1558-62. doi: 10.1111/j.1572-0241.2001.03777.x.
Abstract/Text OBJECTIVES: To assess the tolerability and efficacy of high-dose (25-30 mg/kg per day) ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC).
METHODS: Thirty patients with PSC were enrolled in this pilot study and treated for 1 yr. Changes in the Mayo risk score at 1 yr of treatment and projected survival at 4 yr were compared with that observed in patients randomized to placebo (n = 52) or UDCA (n = 53) at a dose of 13-15 mg/kg per day.
RESULTS: A marked improvement in serum alkaline phosphatase activity (1265+/-172 vs 693+/-110 U/L, p < 0.001), AST (161+/-037 vs 77+/-13 U/L, p = 0.001), albumin (4.0+/-0.1 vs 4.2+/-0.1 g/dl, p = 0.03), and total bilirubin (1.6+/-0.3 vs 1.3+/-0.2 mg/dl, p = 0.1) occurred at 1 yr of therapy with high-dose UDCA. Changes in the Mayo risk score after 1 yr of treatment were significantly different among the three groups (p < 0.001), and these changes would be translated into a significantly different expected survival at 4 yr (p = 0.05). This expected survival at 4 yr was significantly different between placebo and the dose of 25-30 mg/kg per day (p = 0.04), but not between placebo and the dose of 13-15 mg/kg per day (p = 0.4). High-dose UDCA was well tolerated.
CONCLUSIONS: UDCA at a dose of 25-30 mg/kg per day may be of benefit for patients with PSC, and this regimen deserves further evaluation in a long-term, randomized, placebo-controlled trial.

PMID 11374699  Am J Gastroenterol. 2001 May;96(5):1558-62. doi: 10.111・・・
著者: Jian Shi, Zhi Li, Xin Zeng, Yong Lin, Wei-Fen Xie
雑誌名: Hepatol Res. 2009 Sep;39(9):865-73. doi: 10.1111/j.1872-034X.2009.00527.x. Epub 2009 May 7.
Abstract/Text AIMS: The effect of ursodeoxycholic acid (UDCA) treatment on survival and liver histological progression of primary sclerosing cholangitis (PSC) remains uncertain. The aim of the present study was to evaluate the effect and safety of UDCA in PSC.
METHODS: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science and PubMed (updated to January 2009) and manual bibliographical searches were carried out. A meta-analysis of all randomized controlled trials (RCT) comparing UDCA with placebo or no treatment was carried out.
RESULTS: Eight RCT including 465 patients were assessed. UDCA could significantly improve liver biochemistry, but had no effect on pruritus and fatigue. Meta-analysis of the included RCT showed UDCA had no significant effect on the incidence of death, liver transplantation, and death and/or liver transplantation. However, a significant difference for the incidence of histological improvement was found between the two groups (odds ratio [OR], 9.19; 95% CI: 0.98, 86.15; P = 0.05). Meta-analysis also indicated a reduction trend of histological deterioration and an improvement trend of cholangiographic changes. These trends were constant in the sensitivity analyses.
CONCLUSION: The meta-analysis found that UDCA can improve liver biochemistry and there is a trend towards improvement in liver histology and cholangiography, but has no effect on survival free of transplantation.

PMID 19467021  Hepatol Res. 2009 Sep;39(9):865-73. doi: 10.1111/j.1872・・・
著者: C K Triantos, N M Koukias, V N Nikolopoulou, A K Burroughs
雑誌名: Aliment Pharmacol Ther. 2011 Oct;34(8):901-10. doi: 10.1111/j.1365-2036.2011.04822.x. Epub 2011 Aug 22.
Abstract/Text BACKGROUND: There is no satisfactory medical treatment for patients with primary sclerosing cholangitis. There are conflicting data regarding the clinical benefit of high doses of ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis.
AIM: To evaluate using meta-analysis, if UDCA (standard or high-dose) is useful in primary sclerosing cholangitis.
METHODS: We searched MEDLINE using the textwords 'PSC', 'treatment', 'UDCA' and retrieved all abstracts from the major Gastroenterology and Liver meetings. We included randomised clinical trials comparing standard or high-dose of UDCA (>15 mg/kg body weight per day) vs. placebo or no intervention. End-points: mortality or liver transplantation, pruritus, fatigue, cholangiocarcinoma and histological progression.
RESULTS: We identified eight randomised clinical trials comprising 567 patients. Five used standard doses and three high doses of UDCA. There was no significant difference in mortality [OR, 0.6 (95% CI, 0.4-1.4)], in pruritus [OR, 1.5 (95% CI, 0.3-7.2)], in fatigue [OR, 0.0 (95% CI, 0.1-7.7)], in cholangiocarcinoma [OR, 1.7 (95% CI, 0.6-5.1)] and in histology stage progression [OR, 0.9 (95% CI, 0.34-2.44)]. No differences were found in the subgroup analyses.
CONCLUSION: Neither standard nor high-dose UDCA influence favourably the progression of primary sclerosing cholangitis.

© 2011 Blackwell Publishing Ltd.
PMID 21883323  Aliment Pharmacol Ther. 2011 Oct;34(8):901-10. doi: 10.・・・
著者: Ryuichi Kita, Yuri Kita-Sasai, Ikuko Hanaoka, Toru Kimura, Hiroyuki Kokuryu, Seigo Takamatsu, Yukio Osaki, Naomi Tomono, Tsutomu Hachiya, Tatsuo Shimizu
雑誌名: Am J Gastroenterol. 2002 Jul;97(7):1849-51. doi: 10.1111/j.1572-0241.2002.05869.x.
Abstract/Text
PMID 12135056  Am J Gastroenterol. 2002 Jul;97(7):1849-51. doi: 10.111・・・
著者: Takeshi Kurihara, Atsushi Maeda, Mutsuo Shigemoto, Katsuko Yamashita, Naoyuki Kamatani
雑誌名: J Gastroenterol. 2003;38(3):300-1.
Abstract/Text
PMID 12693383  J Gastroenterol. 2003;38(3):300-1.
著者: Ryuichi Kita, Seigo Takamatsu, Toru Kimura, Hiroyuki Kokuryu, Yukio Osaki, Naomi Tomono
雑誌名: J Gastroenterol. 2006 Jul;41(7):686-92. doi: 10.1007/s00535-006-1831-0.
Abstract/Text BACKGROUND: Bezafibrate is a commonly used medicine for hyperlipidemia, and recently several reports have suggested the efficacy of bezafibrate for the treatment of primary biliary cirrhosis (PBC). To assess its efficacy for other liver diseases, we administered bezafibrate to patients with various categories of hepatobiliary impairment.
METHODS: Bezafibrate (400 mg/day) was orally administered to 67 patients with chronic liver disease [22 with PBC, six with primary sclerosing cholangitis (PSC), 20 with chronic liver disease associated with hepatitis C virus (HCV) infection (CLD-C), seven with auto immune hepatitis (AIH), ten with alcoholic liver injury, and two with drug-induced liver injury].
RESULTS: The levels of biliary enzymes, such as alkaline phosphatase and gamma-glutamyltranspeptidase, decreased promptly and dramatically. The abnormally high level of alanine aminotransferase also showed a gradual decrease over 6 months in five of the eight PBC patients, all three PSC patients, eight of the 17 CLD-C patients, and all seven alcoholic liver injury patients. The level of immunoglobulin M showed a gradual decrease in 17 of the 22 PBC patients.
CONCLUSIONS: Bezafibrate significantly reduced the level of biliary enzymes in various chronic liver diseases and may be useful for the treatment of certain liver disease subsets.

PMID 16933007  J Gastroenterol. 2006 Jul;41(7):686-92. doi: 10.1007/s0・・・
著者: Suguru Mizuno, Kenji Hirano, Minoru Tada, Keisuke Yamamoto, Yoko Yashima, Hiroshi Yagioka, Kazumichi Kawakubo, Yukiko Ito, Hirofumi Kogure, Takashi Sasaki, Toshihiko Arizumi, Osamu Togawa, Saburo Matsubara, Yousuke Nakai, Naoki Sasahira, Takeshi Tsujino, Hiroyuki Isayama, Takao Kawabe, Masao Omata, Kazuhiko Koike
雑誌名: J Gastroenterol. 2010 Jul;45(7):758-62. doi: 10.1007/s00535-010-0204-x. Epub 2010 Feb 3.
Abstract/Text BACKGROUND: It is known that bezafibrate decreases serum alkaline phosphatase (ALP) in patients with hyperlipidemia, and the efficacy of this drug for the treatment of primary biliary cirrhosis has been confirmed. However, there has been little evidence of its efficacy for the treatment of primary sclerosing cholangitis (PSC).
METHODS: Bezafibrate (400 mg/day) was orally administered to 7 consecutive patients with PSC, and we analyzed their clinical features and the drug efficacy in terms of the effect on hepatobiliary enzymes, including ALP, gamma-glutamyl transpeptidase (gamma-GTP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 6 months. The latest hepatobiliary enzyme levels were also evaluated.
RESULTS: In 3 patients (effective group), the levels of all hepatobiliary enzymes had decreased after 6 months. Mean ALP had decreased to approximately 40% of the baseline in this group. The efficacy of bezafibrate was observed for a long period (range, 8-27 months) in these 3 patients. There seemed to be no definite association between the efficacy of bezafibrate and the clinical features in the short term.
CONCLUSIONS: This study showed that bezafibrate could lower the levels of hepatobiliary enzymes in about half of a cohort of patients with PSC.

PMID 20127368  J Gastroenterol. 2010 Jul;45(7):758-62. doi: 10.1007/s0・・・
著者: J A Goss, C R Shackleton, D G Farmer, W S Arnaout, P Seu, J S Markowitz, P Martin, R J Stribling, L I Goldstein, R W Busuttil
雑誌名: Ann Surg. 1997 May;225(5):472-81; discussion 481-3.
Abstract/Text OBJECTIVE: The purpose of this study was to analyze a single center's 12-year experience with 127 orthotopic liver transplantations (OLT) for primary sclerosing cholangitis (PSC).
SUMMARY BACKGROUND DATA: Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown origin that occurs most commonly in young men and is associated frequently (70-80%) with inflammatory bowel disease (IBD). Patients with PSC also are at risk for the development of cholangiocarcinoma (CCA) and those with IBD for colon carcinoma. Although the course of PSC is variable, it frequently is progressive, leading to cirrhosis and requirement for OLT.
METHODS: The medical records of 127 consecutive patients undergoing OLT for PSC from July 1, 1984, to May 30, 1996, were reviewed. Actuarial patient and graft survival was determined at 1,2, and 5 years. The incidence and outcome of patients with CCA, recurrent sclerosing cholangitis, and post-transplant colon carcinoma was determined. Results were analyzed by way of stepwise Cox regression to determine the statistical strength of independent associations between pretransplant covariates and patient survival. The median follow-up period was 3.01 years. Incidental cholangiocarcinoma (ICCA) was defined as a tumor < 1 cm in size that was discovered at the time of pathologic sectioning of the explanted liver.
RESULTS: Ninety-two patients (72%) had associated IBD. Seventy-nine (62%) had undergone previous biliary tract surgery. One hundred seven patients (84%) received a single graft, whereas 20 patients (16%) required 22 retransplants. Patients received either cyclosporine- (n = 76) or tacrolimus- (n = 51) based immunosuppression. The 1-, 2-, and 5-year actuarial patient survivals were 90%, 86%, and 85%, respectively, whereas graft survival was 82%, 77%, and 72%, respectively. The presence of previous biliary surgery had no effect on patient survival. Ten patients (8%) had ICCA and their survival was not significantly different from patients without ICCA (100%, 83%, and 83% at 1, 2, and 5 years, respectively). Four patients were known to have CCA at the time of OLT, all recurred within 6 months, and had a significantly worse outcome (p < 0.0001). Recurrent sclerosing cholangitis developed in 11 patients (8.6%). The patient and graft survival in this group was not different from those in whom recurrence did not develop (patient; 100%, 90%, and 90%; graft: 80%, 70%, and 52%). Thirty patients (23%) underwent colectomy after liver transplantation for dysplasia-carcinoma or symptomatic colitis. Of the nine covariates entered into the Cox multivariate regression analysis, only common bile duct frozen section biopsy specimen showing CCA was predictive of a survival disadvantage.
CONCLUSIONS: Liver transplantation provides excellent patient and graft survival rates for patients affected with PSC independent of pretransplant biliary tract surgery. Incidental cholangiocarcinoma does not affect patient survival significantly. However, known CCA or common duct frozen section biopsy specimen or both showing CCA are associated with poor recipient survival, and OLT should be proscribed in these cases. Recurrent PSC occurs in approximately 9% of cases but does not affect patient survival. Post-transplant colectomy does not affect patient survival adversely.

PMID 9193175  Ann Surg. 1997 May;225(5):472-81; discussion 481-3.
著者: H Egawa, Y Ueda, T Ichida, S Teramukai, Y Nakanuma, S Onishi, H Tsubouchi
雑誌名: Am J Transplant. 2011 Mar;11(3):518-27. doi: 10.1111/j.1600-6143.2010.03402.x. Epub 2011 Jan 10.
Abstract/Text The outcomes of primary sclerosing cholangitis (PSC) after living donor liver transplantation (LDLT) in a large series have not been reported. We aimed to determine long-term patient and graft survival, risk factors for PSC recurrence, and the significance of recurrence after LDLT in a Japanese registry. Questionnaires concerning patient characteristics, treatments, and clinical courses were used. Data of 114 patients undergoing primary LDLT for PSC from July 1996 to December 2008 in 29 institutions were evaluated. For strict diagnoses of recurrence, patients with hepatic artery thrombosis (n = 8), ABO-blood-type-incompatible transplantation (n = 8), and established ductopenic rejection (n = 2) were excluded and 96 patients were analyzed for risk factors. Recurrence was diagnosed in 26 patients (27%) at 8 to 79 months after transplantation. Patient, graft, and recurrence-free survivals were 78, 74 and 57% at 5 years after LDLT, respectively. The graft loss rate was 69 versus 23% in patients with versus without recurrence, respectively. Multivariate analysis revealed that high MELD scores, first-degree-relative donors, postoperative CMV infection, and early biliary anastomotic complications were significant risk factors for recurrence. PSC recurrence was a significant risk factor of graft loss but not patient death. PSC recurrence was frequent and had significant impacts on outcomes after LDLT.

©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
PMID 21219581  Am J Transplant. 2011 Mar;11(3):518-27. doi: 10.1111/j.・・・

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