自己免疫性肝疾患
自己免疫学的機序で肝障害をきたす疾患の総称であり、自己免疫性肝炎(AutoImmune Hepatitis:AIH)・原発性胆汁性胆管炎(Primary Biliary Cholangitis:PBC)・原発性硬化性胆管炎(Primary Sclerosing Cholangitis:PSC)が含まれる。
肝細胞(肝実質)が障害されるものが自己免疫性肝炎、肝内胆管が障害されるものが原発性胆汁性胆管炎、肝内胆管・肝外胆管が障害されるものが原発性硬化性胆管炎である。
原発性胆汁性胆管炎と原発性硬化性胆管炎は胆管の障害により慢性胆汁うっ滞性肝障害をきたす。
自己免疫性肝疾患は慢性の経過を辿り、初期には無症候なことも多い。患者は健康診断で肝機能異常を指摘されて来院することが多い。
しかし、適切な治療がされないと最終的には肝硬変となる。高度に肝機能が障害された場合は肝移植が視野に入る。
自己免疫性肝炎(AutoImmune Hepatitis:AIH)
自己免疫学的機序によって肝細胞が障害されて起こる疾患であり、中高年の女性に好発する。
検査所見
特異的な自己抗体
抗平滑筋抗体・抗核抗体が陽性となる。
肝逸脱酵素・胆道系酵素
肝逸脱酵素であるAST・ALTは上昇するが、胆道系酵素であるALP・γ-GTPは上昇せずに正常となる。
免疫グロブリン
IgG血中濃度上昇を認める。
病理組織像
ロゼット形成・リンパ濾胞の形成
ロゼット形成とは淡明化した肝細胞がロゼット状(花弁状)に集積する病理像を指す。
その他の所見
HLA-DR4が高頻度に陽性となる。
治療
副腎皮質ステロイドが有効となる。
原発性胆汁性胆管炎(Primary Biliary Cholangitis:PBC)
自己免疫学的機序によって肝内胆管が障害されて起こる疾患であり、中高年の女性に好発する。高ビリルビン血症による瘙痒や黄疸が主訴となることが多い。
検査所見
特異的な自己抗体
抗ミトコンドリア抗体が陽性となる。
肝逸脱酵素・胆道系酵素
病態が進行していると肝逸脱酵素(AST・ALT)も上昇しがちだが、肝酵素よりも胆道系酵素(ALP・γ-GTP)の上昇が著明で目立つ。
免疫グロブリン
IgM血中濃度上昇
病理組織像
小葉間胆管の減少と慢性炎症性細胞であるリンパ球の高度浸潤を特徴とする慢性非化膿性破壊性胆管炎を認める。
急性炎症性細胞である好中球浸潤が主体となる化膿性炎ではないことに注意する。
画像検査所見
画像検査では捉えることのできない細小な小葉間胆管の障害であるため特異的な画像検査所見はない。
合併しやすい疾患
Sjögren症候群
Sjögren症候群などの自己免疫性疾患を合併しやすい。
高度肝障害に伴う疾患(食道胃静脈瘤)
原発性胆汁性胆管炎が肝硬変を併発すると門脈圧が上昇して食道胃静脈瘤などを合併する可能性がある。ちなみに原発性胆汁性胆管炎は数年前までは原発性胆汁性肝硬変という名前だった。
これは昔は診断技術が発達しておらず、診断されたときにはほぼ終末像で肝硬変を伴っていた患者が多かったからという理由がある。しかし、現代においてはこの病気で実際に肝硬変まで進行する方は全体の1割にも満たないことから実態に見合わないということで名前が変更されたという経緯がある。
胆汁うっ滞による合併症(骨粗鬆症)
脂質を消化して吸収しやすくする胆汁が適切に働かないため、脂質が吸収されにくくなる。
このため、脂溶性ビタミンであるビタミンDも吸収しづらくなり不足する。ビタミンDが不足すると骨粗鬆症が起こる。
高コレステロール血症
胆汁うっ滞は胆汁の流出または生成の障害により、通常は胆汁中に排出される物質の血中濃度上昇をきたす。胆汁うっ滞疾患である原発性胆汁性胆管炎や原発性硬化性胆管炎では血中コレステロール値が上昇することが知られている。
治療
胆汁酸製剤のウルソデオキシコール酸には胆汁うっ滞改善効果があり、第一選択薬となる。
副腎皮質ステロイドは無効である。
原発性硬化性胆管炎(Primary Sclerosing Cholangitis:PSC)
自己免疫学的機序によって肝内胆管・肝外胆管が障害されて起こる疾患であり、20～30代男性に好発する。
検査所見
特異的な自己抗体
特異的な自己抗体が存在しない。
肝逸脱酵素・胆道系酵素
病態が進行していると肝酵素(AST・ALT)も上昇しがちだが、肝酵素よりも胆道系酵素(ALP・γ-GTP)の上昇が著明で目立つ。
免疫グロブリン
IgM血中濃度上昇を認める。
病理組織像
胆管周囲の輪状線維化:onion-skin lesionを特徴とする。
画像検査所見
内視鏡的逆行性胆道膵膵管造影(ERCP)
内視鏡的逆行性胆道膵管造影(ERCP)で胆管の狭窄と拡張による数珠様変化を認める。
合併しやすい疾患
潰瘍性大腸炎・胆管細胞癌を合併しやすい。
治療
胆汁酸製剤のウルソデオキシコール酸には胆汁うっ滞改善効果があり、第一選択薬となる。副腎皮質ステロイドは無効である。
参考文献
原発性胆汁性胆管炎(PBC)診療ガイドライン(2017年):https://minds.jcqhc.or.jp/docs/minds/primary-billary-cholangiti/primary-billary-cholangiti.pdf
自己免疫性肝炎(AIH)診療ガイドライン:https://minds.jcqhc.or.jp/docs/gl_pdf/G0001350/4/autoimmune_hepatitis.pdf
原発性胆汁性胆管炎:https://www.kyorin-pharm.co.jp/prodinfo/useful/doctorsalon/upload_docs/190863-1-06.pdf
原発性胆汁性肝硬変の治療戦略:https://tmu.repo.nii.ac.jp/?action=repository_action_common_download&item_id=11480&item_no=1&attribute_id=22&file_no=1
硬化性胆管炎の病理:https://www.jstage.jst.go.jp/article/tando/22/5/22_5_658/_pdf/-char/ja
病理像による原発性硬化性胆管炎の鑑別診断:https://core.ac.uk/download/pdf/196712818.pdf
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Adams, Paul. “Could a Coffee Maker Be Worth $11,000?” Slate.
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Ramsey, Geoffrey. “Study: US Marijuana Legalization Could Cut Cartel Profits By 30.” InSight Crime.
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