Eckstein R P, Dowsett J F, Lunzer M R
Department of Anatomical Pathology, Royal North Shore Hospital, St. Leonards, Sydney NSW.
Pathology. 1993 Jul;25(3):223-8. doi: 10.3109/00313029309066576.
The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.
本文呈现了13例在使用氟氯西林治疗后发生胆汁淤积的患者肝脏活检的组织学表现。在大多数病例中，黄疸和瘙痒持续时间较长，并且在平均随访18个月后，几乎所有病例的肝功能检查仍未恢复正常。1例患者在黄疸出现7个月后死亡，另1例有继发性胆汁性肝硬化的临床证据。活检通常显示肝细胞和胆小管胆汁淤积，肝炎轻微或无肝炎表现。通常存在轻度门静脉纤维化和散在的门静脉淋巴细胞浸润。4例患者胆管数量减少，6例患者胆管尺寸减小。胆管上皮显示退行性改变，但仅有偶尔的炎性细胞浸润。小胆管增生变化很大，在某些病例中——最明显的是致命病例——尽管胆管减少，但小胆管增生并不明显。这些表现提示不仅肝细胞受损，胆管和增生的小胆管也受损。这可能解释了与使用氟氯西林相关的迁延性且偶尔不可逆的肝脏疾病。氟氯西林应被列入消失胆管综合征的病因之中。
