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Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America
H L Bonkovsky1, M Poh-Fitzpatrick, N Pimstone
1University of Massachusetts Medical Center, and Center for Study of Disorders of Iron and Porphyrin Metabolism, Worcester 01655, USA.
Insights
Porphyria cutanea tarda (PCT) in North America is frequently linked to Hepatitis C Virus (HCV) infection and HFE gene mutations. Testing for both HCV and HFE mutations is recommended for all PCT patients.
Area of Science:
- Hepatology
- Genetics
- Dermatology
Background:
- Porphyria cutanea tarda (PCT) is associated with Hepatitis C Virus (HCV) infection and HFE gene mutations in some regions.
- Few studies have investigated these associations in North America.
Purpose of the Study:
- Assess HCV infection and HFE mutation prevalence in North American PCT patients.
- Compare demographics and lab features between HCV-positive and negative PCT patients.
- Examine urinary porphyrin excretion in HCV-positive patients without PCT.
Main Methods:
- Collected clinical and laboratory data from 70 PCT patients.
- Tested for HCV infection and measured urinary porphyrins.
- Performed HFE gene mutational analyses on 26 PCT patients.
- Measured urinary porphyrins in 110 chronic HCV patients without PCT.
Main Results:
- 56% of PCT patients were HCV-positive; 73% carried HFE mutations (C282Y or H63D).
- HCV-positive PCT patients were more likely to report drug use and multiple sexual partners.
- Urinary porphyrin profiles differed between HCV-positive and negative PCT patients.
- 15% of HCV-positive patients without PCT had elevated urinary porphyrins, primarily coproporphyrin.
Conclusions:
- HCV infection and HFE gene mutations are highly prevalent in North American PCT patients.
- Alcohol and estrogen use are significant additional risk factors for PCT.
- Testing for HCV and HFE mutations is recommended for all PCT patients.
- Preclinical PCT is uncommon in chronic HCV patients in the US.
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. 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.