Bonkovsky H L, Poh-Fitzpatrick M, Pimstone N, Obando J, Di Bisceglie A, Tattrie C, Tortorelli K, LeClair P, Mercurio M G, Lambrecht R W
University of Massachusetts Medical Center, and Center for Study of Disorders of Iron and Porphyrin Metabolism, Worcester 01655, USA.
Hepatology. 1998 Jun;27(6):1661-9. doi: 10.1002/hep.510270627.
In some, but not all countries, porphyria cutanea tarda (PCT) has been associated with chronic infection with the hepatitis C virus (HCV). Recently, PCT has also been associated with mutations in the HFE gene that are associated with HLA-linked hereditary hemochromatosis. Until now, few studies of these associations have been reported from North America. The aims of this study were: 1) to assess the prevalence of HCV infection and HFE mutations in North American patients with PCT; 2) to compare demographic and laboratory features between those who are HCV-positive and HCV-negative; and 3) to study urinary porphyrin excretions in American HCV-positive patients without clinically manifest PCT. Clinical and laboratory data, including tests for HCV and urinary porphyrins, were collected from 70 unselected patients with typical PCT. Urinary porphyrins were also measured in 110 non-PCT patients with chronic hepatitis C. Mutational analyses of the HFE gene were performed in 26 PCT patients. Thirty-nine of 70 (56%) of the PCT patients had evidence of HCV infection. Thirty-two of 39 PCT patients with HCV were men, all of whom used alcohol. In contrast, 22 of 31 PCT patients without HCV infection were women, 12 of whom had taken estrogens. The HCV-positive group was more likely to have used illicit intravenous drugs (45% vs. 0%; P = 0.01), to have had several (>4) sex partners (48% vs. 13%; P = 0.005), and less likely to have no known risk factors for HCV infection (33% vs. 78%; P = 0.004). Total urinary porphyrin excretion was the same in the two groups, but those with HCV infection had a significantly lower percentage of uroporphyrin and higher percentages of hepta-and hexa-carboxy porphyrins in urine. Sixteen of 110 (15%) HCV-positive subjects without PCT had increased urinary porphyrins, but, unlike PCT, these were mainly coproporphyrin. Forty-two percent of PCT patients carried the C282Y mutation of HFE (15% homozygous), and another 31% carried the H63D mutation (8% homozygous). Thus, 73% of PCT patients had one of these mutations. The prevalence of HCV infection (56%) and mutations in the HFE gene (73%) are high among North American patients with PCT. Alcohol and estrogen use are important additional risk factors. All PCT patients should be tested for HCV infection and for HFE gene mutations. Although HCV infection is a trigger for PCT, preclinical PCT is rare in chronic HCV hepatitis C in the United States.
在部分（但并非全部）国家，迟发性皮肤卟啉症（PCT）与丙型肝炎病毒（HCV）慢性感染有关。最近，PCT还与HFE基因突变有关，而该突变与HLA连锁的遗传性血色素沉着症相关。到目前为止，北美地区关于这些关联的研究报道较少。本研究的目的是：1）评估北美PCT患者中HCV感染和HFE突变的患病率；2）比较HCV阳性和HCV阴性患者的人口统计学和实验室特征；3）研究美国无临床症状PCT的HCV阳性患者的尿卟啉排泄情况。收集了70例未经挑选的典型PCT患者的临床和实验室数据，包括HCV检测和尿卟啉检测。还对110例非PCT慢性丙型肝炎患者进行了尿卟啉测定。对26例PCT患者进行了HFE基因突变分析。70例PCT患者中有39例（56%）有HCV感染证据。39例HCV阳性的PCT患者中有32例为男性，均有饮酒史。相比之下，31例无HCV感染的PCT患者中有22例为女性，其中12例曾使用过雌激素。HCV阳性组更有可能使用过非法静脉注射药物（45%对0%；P = 0.01），有多个（>4个）性伴侣（48%对13%；P = 0.005），且无已知HCV感染危险因素的可能性较小（33%对78%；P = 0.004）。两组的尿卟啉总排泄量相同，但HCV感染患者尿中的尿卟啉百分比显著较低，而七羧基和六羧基卟啉百分比较高。110例无PCT的HCV阳性受试者中有16例（15%）尿卟啉增加，但与PCT不同的是，这些主要是粪卟啉。42%的PCT患者携带HFE基因的C282Y突变（15%为纯合子），另有31%携带H63D突变（8%为纯合子）。因此，73%的PCT患者有这些突变之一。北美PCT患者中HCV感染（56%）和HFE基因突变（73%）的患病率较高。饮酒和使用雌激素是重要的附加危险因素。所有PCT患者均应进行HCV感染检测和HFE基因突变检测。虽然HCV感染是PCT发病诱因，但在美国慢性丙型肝炎中，临床前PCT很少见。
