Kunze K D, Porst H, Lohmann J, Tschöpel L
Zentralbl Allg Pathol. 1985;130(1):19-29.
The antihypertensive drugs dihydralazine and propranolol can produce identical liver injuries which must be distinguished clinically and morphologically from acute viral hepatitis. In 19 cases selected from our biopsy file during the last two years, clinical and morphological findings suggested that the liver injury diagnosed by light microscopy had been caused by an adverse reaction to dihydralazine and/or propranolol. In order to establish a causal relation the lymphocyte proliferation test (LPT) was performed with dihydralazine in 11 cases. Positive results were observed in 9 cases, demonstrating an etiologic role for dihydralazine in liver injury in these cases. The dihydralazine and/or propranolol induced liver injury consisted mainly of drug-induced hepatitis with confluent (bridging) necrosis. Different findings were observed in three cases: In two of these drug-induced hepatitis with confluent necrosis was observed together with eosinophilic cholangio-cholangiolitis. In one other case the histologic changes corresponded to drug hepatitis resembling viral hepatitis. Each of the three cases showed conspicuous centrolobular cholestasis, a feature which is unusual in drug-induced hepatitis with confluent necrosis irrespective of serum bilirubin levels. In one third of our cases we found morphological features of hypersensitivity reactions in the liver biopsies. Considered together with the results of LPT these features emphasize the role of cell mediated immune reaction in the mechanism of liver injury caused by dihydralazine and/or propranolol.
抗高血压药物双肼屈嗪和普萘洛尔可导致相同的肝损伤,这种损伤在临床和形态学上必须与急性病毒性肝炎相区分。在过去两年从我们的活检档案中选取的19例病例中,临床和形态学检查结果提示,经光学显微镜诊断的肝损伤是由双肼屈嗪和/或普萘洛尔的不良反应所致。为了确定因果关系,对11例病例进行了双肼屈嗪淋巴细胞增殖试验(LPT)。9例结果呈阳性,表明双肼屈嗪在这些病例的肝损伤中起病因作用。双肼屈嗪和/或普萘洛尔所致肝损伤主要为药物性肝炎伴融合性(桥接)坏死。在3例病例中观察到不同的表现:其中2例观察到药物性肝炎伴融合性坏死与嗜酸性胆管-胆小管炎同时存在。另一例的组织学改变符合类似病毒性肝炎的药物性肝炎。这3例病例均显示明显的小叶中心性胆汁淤积,无论血清胆红素水平如何,这一特征在伴有融合性坏死的药物性肝炎中并不常见。在我们三分之一的病例中,肝活检发现了超敏反应的形态学特征。结合LPT结果来看,这些特征强调了细胞介导的免疫反应在双肼屈嗪和/或普萘洛尔所致肝损伤机制中的作用。