STUDIES IN PORPHYRIA CUTANEA TARDA

迟发性皮肤卟啉病(Porporria cutanea tarda，PCT)是最常见的一种，是由于肝脏中的尿卟啉原脱羧酶明显缺乏所致。在PCT中发现的尿卟啉原脱羧酶缺乏症主要是获得性的。本研究的目的如下。1.通过测量血清和白细胞中的维生素C水平来评估标准治疗(重复采血或小剂量氯喹)前后的维生素C状况。这将检验一种假设，即维生素C是肝脏中的一种抗氧化剂，其缺乏可能有助于PCT的激活。2.通过~(13)C-咖啡因和~(13)C-美沙西丁呼气试验，以及通过测定咖啡因从血和尿中的清除率以及咖啡因代谢物的尿液排泄量来评估CYP 1A2的体内活性。3.丙型肝炎感染的作用是通过以下方式来评估的：(A)观察反复放血或小剂量氯喹治疗PCT对肝功能检查异常以及血浆中丙型肝炎抗体和丙型肝炎RNA存在的影响；以及(B)观察接受干扰素x-2b治疗的患者与未接受该药物治疗的患者PCT复发的频率。标准的血清化学和[13C]苯丙氨酸呼气试验被用来评估肝功能。干扰素x-2b的治疗适应症将是丙型肝炎患者使用这种药物的标准适应症，不会受到本方案的影响或指定。患者首先接受PCT的治疗，因为PCT的治疗几乎总是成功的，而丙型肝炎的治疗通常不成功。

Porphyria cutanea tarda (PCT) is the most common of the porphyrias and is due to a marked deficiency of uroporphyrinogen decarboxylase in liver. The uroporphyrinogen decarboxylase deficiency found in PCT is primarily acquired. The aims of this study are as follows. 1. Vitamin C status is assessed before and after standard treatment (either repeated phlebotomy or low-dose choloroquine) by measuring vitamin C levels in serum and white blood cells. This will test the hypothesis that vitamin C is an antioxidant in the liver and that its deficiency may contribute to activation of PCT. 2. Activity of CYP 1A2 is assessed in vivo using 13C-caffeine and 13C-methacetin breath tests and also by measuring the clearance rate of caffeine from blood and urinary excretion of caffeine metabolites. 3. The role of hepatitis C infection is assessed by (a) observing the effect of treatment of PCT by repeated phlebotomy or low-dose chloroquine on abnormalities in liver function tests and on the presence of hepatitis C antibody and hepatitis C RNA in plasma; and (b) by observing the frequency of recurrence of PCT in patients who are treated with interferon x-2b as compared to patients who are not treated with this drug. Standard serum chemistries as well as a [13C]phenylaline breath test are used to assess liver function. The indications for treatment with interferon x-2b will be the standard indications for use of this drug in patients with hepatitis C and will not be influenced or specified by this protocol. Patients are treated first for PCT, because treatment for PCT is almost always successful, whereas treatment for hepatitis C is usually not.