STUDIES IN PORPHYRIA CUTANEA TARDA

迟发性皮肤卟啉症（PCT）是最常见的卟啉症，是由于肝脏中尿卟啉原脱羧酶的明显缺乏。在PCT中发现的尿卟啉原脱羧酶缺乏主要是获得性的。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，在标准治疗（反复放血或低剂量氯喹）前后评估维生素C状态。这将验证维生素C在肝脏中是一种抗氧化剂的假设，维生素C的缺乏可能会导致PCT的激活。体内使用13c -咖啡因和13C-methacetin呼气试验评估CYP 1A2的活性，也通过测量血液中咖啡因的清除率和尿液中咖啡因代谢物的排泄来评估。3. 丙型肝炎感染的作用是通过(a)观察反复放血或低剂量氯喹治疗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存在的影响来评估的；(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的PCT复发频率。标准血清化学以及[13C]苯胺呼气试验被用来评估肝功能。干扰素x-2b治疗的适应症将是丙型肝炎患者使用该药物的标准适应症，不受本方案的影响或规定。患者首先接受PCT治疗，因为PCT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.