Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in north america†

Abstract

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. Thirtynine 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 (G4) 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. (HEPATOLOGY 1998;27:1661-1669.)

C282Y and H63D mutations in the HFE gene are not associated with porphyria cutanea tarda in bulgaria

“…2 The second missense mutation, H63D, was caused by a C to G transversion at 187 nucleotides of the open reading frame. A role for genetic hemochromatosis in the pathogenesis of iron overload in PCT has been also suggested, 3 and high association of HFE and PCT has been reported in Italian 4 as well as in British patients. 5 Although HH is common in populations of Northern European origin, with frequency of 1 of 200 to 1 of 300, 6 it is rare in African, Asian, and Australian populations.…”

“…Population studies to establish an association between the 2 principal HFE mutations 1,2 and sporadic porphyria cutanea tarda (SPCT) 3 have led to varying results. Roberts et al 4 found the C282Y mutation in 18 of 41 (44%) British patients with SPCT, 7 of whom (17%) were homozygous.…”

“…In contrast, a 50% prevalence of this mutation either in its heterozygous or homozygous form was recently reported by Sampietro et al 6 in 68 Italian patients, whereas the C282Y mutation was found in only 3%. In North America, Bonkovsky et al 3 found that 42% of the PCT individuals carried the C282Y mutation (15% homozygous) whereas the H63D mutation was detected in 31% (8% homozygous). We have examined this question in a population from Southeastern Europe.…”

Porfiria cutânea tardia

“…66 These patients have additional benefit from phlebotomy, because lowering iron improves hepatic inflammation and response to interferon treatment. 67 There must be a predisposition for Urod deficiency, because most patients with hepatitis C do not develop PCT. 68 As PCT may be the first indication of an HCV infection, it is important to be searched in all patients.…”

Host genetic determinants in hepatitis C virus infection

“…1,5,6 Some individuals with chronic HCV develop a number of extrahepatic comorbidities, ranging from autoimmune manifestations to disorders such as diabetes. [7][8][9][10] A geographic gradient with respect to autoimmune manifestations in HCV may exist. For example, the presence of cryoglobulins and autoantibodies is largely a southern European phenomenon.…”