The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection

OBJECTIVES: To investigate the role of C282Y and H63D mutations, and hepatitis C virus (HCV) infection in the pathogenesis of porphyria cutanea tarda (PCT). DESIGN: Prospective case-control study. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases in Barcelona, Spain. PATIENTS: Ninety-nine consecutive patients with PCT and one hundred and twenty-six control patients (76 healthy subjects and 50 patients chronically infected with HCV), were recruited. MAIN OUTCOME MEASURES: The frequency of the C282Y and H63D mutations in patients with PCT vs. controls and the relationship of these mutations with HCV infection, and iron status, as judged by serum iron, liver iron and ferritin levels. RESULTS: C282Y mutation was significantly increased in PCT patients. This mutation was more frequent among non-HCV-infected patients. Increased ferritin levels and hepatic iron overload were also observed in PCT patients with heterozygous C282Y state. H63D mutation was only significantly increased among PCT patients with chronic hepatitis C infection. No significant iron overload was observed in patients with H63D mutation. CONCLUSIONS: This study confirms the high frequency of C282Y mutation in patients with PCT and its relationship with iron overload. The C282Y mutation has a relevant role in Spanish patients with PCT not associated with HCV chronic infection. On the other hand, the prevalence of the H63D mutation seems not to be increased in patients with PCT. The possibility of an association between HCV infection and H63D mutation in inducing PCT can be hypothesized.     

High prevalence of HFE gene mutations in patients with porphyria cutanea tarda in the Czech Republic

Background  Iron overload and hepatitis C virus (HCV) infection are independent factors which are thought to play a role in the pathogenesis of porphyria cutanea tarda (PCT).
Objectives  To determine the prevalence of the HFE gene mutations p.Cys282Tyr (C282Y), p.His63Asp (H63D) and p.Ser65Cys (S65C), the p.Tyr250X (Y250X) mutation of the TFR2 gene, and HCV infection in patients with PCT in the Czech population, and to make comparison of the iron status among the respective genotypes.
Methods  Iron metabolism indices, results of mutational analysis and serological markers of HCV infection were examined in 63 patients with PCT.
Results  The HFE gene mutations were detected in 70% of patients with PCT compared with 35% in the control group ( P  <   0·001). Mean serum ferritin levels were increased in all genotypes, the highest being in homozygotes for the p.Cys282Tyr mutation. HCV infection was detected in only 8% of patients with PCT.
Conclusions  There was a very high prevalence of the p.Cys282Tyr and p.His63Asp mutations observed in patients with PCT accompanied by mild degrees of iron overload, which was genotype dependent.     

HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France

BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent increase of cellular iron absorption and storage. OBJECTIVES: To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patients with PCT originating from southern France, and to evaluate the relationship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections. METHODS: Thirty-six consecutive patients with either sporadic or familial PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. CONCLUSIONS: This study confirms the high frequency of HFE mutations in patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.     

Role of the hemochromatosis gene in prophyria cutanea tarda. Prospective study of 56 cases]

BACKGROUND: The cause of iron overload in prophyria cutanea tada is unknown. The aim of this work was to determine the frequency of the hemochromatosis gene (HFE) in 56 patients with porphyria cutanea tarda. We analyzed the relationship between HFE mutations and biochemical abnormalities in porphyria cutanea tarda and the interaction with other triggering factors of porphyria cutanea tarda (alcohol abuse, hepatitis C, drugs).PATIENTS AND METHODS: Hepatitis C, alcohol abuse, drug intake and HFE mutations were determined in 56 patients with porphyria cutanea tarda (44 men and 12 women). Iron status was determined from transferrin saturation, serum iron, and serum ferritin. Liver metabolism was determined from liver chemistries: alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase.RESULTS: Thirty-nine patients (69.4 p. 100) carried HFE mutations, 18 (32.1 p. 100) were H63D heterozygous, 4 (7.1 p. 100) were H63D homozygous, 9 (16 p. 100) C282Y heterozygous, 8 (14.2 p. 100) compound C282Y/H63D heterozygous and none were C282Y homozygous. Comparison between porphyria cutanea tarda with and without mutations showed that compound C282Y/H63D heterozygous status was significantly linked to iron overload: transferrin saturation=0.61 vs 0.39 (p=0.0001) and serum iron=32.9 vs 22.4 (p=0.0046). H63D homozygous status was linked to iron overload but non-significantly: transferrin sturatin=0.53 vs 0.39 (p=0.06). The class with high iron overload (transferrin saturation > 0.45) was not linked with triggering factors of porphyria cutanea tarda. Hepatatic cytolysis was linked to alcohol abuse and hepatitis C but not to HFE mutations.DISCUSSION: The frequencies of HFE mutations in Lyons France are halfway between Anglo-Saxon and Italian papers, highlighting the Celtic origin of C282Y mutation. Compound heterozygous and to a lesser degree H63D homozygous status explained the highest iron overload in our patients. This favors clinical expression of porphyria cutanea tarda. This iron overload due to HFE mutations is a new triggering factor of porphyria cutanea tarda independent of classical triggering factors: mutation of the erythrocytic uroporpyrinogen decarbocylase gene, alcohol abuse, hepatitis C, and drugs.     

Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda

OBJECTIVE: To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. DESIGN: We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. SETTINGS: Academic teaching hospital. INTERVENTION: For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). RESULTS: Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. CONCLUSIONS: The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.     

Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients

BACKGROUND

Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil.

OBJECTIVES

Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations.

METHODS

An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR.

RESULTS

Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors.

CONCLUSIONS

Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients     

Porphyria cutanea tarda in south-east New South Wales

Thirteen patients with porphyria cutanea tarda diagnosed between 1994 and 2000 were reviewed to evaluate the precipitating factors and associations of porphyria cutanea tarda in a regional area of coastal and rural NSW. The majority had more than one precipitating factor, with excess alcohol intake, mutations in the haemochromatosis gene, chronic hepatitis C infection and oestrogen therapy being the most common. Antibodies to the hepatitis C virus were detected in 25% and these patients presented at a younger age. Of the patients tested for the two known haemochromatosis gene mutations, six (46%) had at least one copy of the C282Y mutation. Two (15%) patients were homozygous for the C282Y mutation and two (15%) were compound heterozygous for the C282Y and H63D mutations. All patients responded to venesection, which is the treatment of choice for the majority of patients with porphyria cutanea tarda.     

Porphyria cutanea tarda and hepatitis C virus infection

We studied the prevalence of hepatitis C virus (HCV) infection in 20 Japanese patients with sporadic-type porphyria cutanea tarda (PCT). Seventeen of the 20 patients (85%) had anti-HCV antibodies. Biochemical remission was observed in nine patients, six of whom still had positive HCV RNA copies. These results suggest that HCV infection is a triggering factor for PCT in Japan. However, continuous HCV infection seems to exert little influence on the maintenance of abnormal porphyrin metabolism. Hepatocellular carcinoma (HCC) developed in five of the 17 HCV-positive patients, three of whose PCT was in remission. Four of these patients showed chronic active hepatitis or cirrhosis on liver biopsy. PCT patients with HCV infection should be followed up long-term because of the possibility of HCC. To evaluate the risk of HCC, liver biopsy may be required, even when the patient is in biochemical remission.     

The association of hepatitis C viral infection with porphyria cutanea tarda in the Lothian region of Scotland

Porphyria cutanea tarda (PCT) is believed to be associated with reduced hepatic uroporphyrinogen decarhoxylase activity and risk factors such as alcohol abuse and medication with oral contraceptives and certain other drugs. Recently it has been suggested that hepatitis C virus (HCV) infection may also he associated with PCT. We have therefore reviewed the prevalence of HCV infection in a series of patients with PCT in the Lothian region of Scotland. We identified 12 patients with PCT, all of whom had abnormal liver function tests. Liver histology revealed chronic active hepatitis in six patients, micronodular cirrhosis in lour patients, hepatocellular carcinoma in one patient and normal findings in one HIV positive patient. Out of 12 patients tested, 11 were positive for anti-HCV antibodies by second generation enzyme linked immunosorbent assay (ELISA 2), and by recombinant immunoblot assay (RIBA 2); positive serology was confirmed by polymerase chain reaction (PCR). In a second group of 14 patients with chronic HCV infection matched for age and sex with the PCT patients, all had normal urinary uroporphyrin excretion. We have thus confirmed in Scotland early reports from Spain and Italy that PCT is strongly associated with HCV infection. This could explain the development of inflammatory changes in the liver and progression of liver disease in patients with PCT. Porphyrin metabolism, however, appears normal in patients with chronic HCV infection without PCT.     

Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda

Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.     

Porphyria cutanea tarda and hepatitis C virus: a case-control study and meta-analysis of the literature.

BACKGROUND: Porphyria cutanea tarda (PCT) and hepatitis C virus (HCV) infection have been associated in several reports with the prevalence of HCV exhibiting considerable regional variation. However, most reports were confounded by selection bias and a regional prevalence of HCV in the populations studied. In the United States, only a few cases of this association have been reported to date. OBJECTIVE: We concluded a study to evaluate the association between PCT and HCV in a US population. We used a case-control study design to control the systemic error that may occur during a selecting process or sampling procedure. METHODS: We reviewed the medical records of Wishard Memorial Hospital, a county hospital serving metropolitan Indianapolis, Indiana, to perform a retrospective case-control study of 26 patients with PCT (as case) against 149,756 regional volunteer blood donors (as control-1) and 51 patients receiving methotrexate for psoriasis (as control-2). HCV antibody titers and other liver abnormalities were our main outcome measures. We then performed a weighted meta-analysis of 17 reports that had at least 17 patients in their study populations. RESULTS: Sixteen (94%) of 17 PCT patients tested for HCV were antibody positive. Among blood donors, only 255 or 0.17% were HCV antibody positive (P < 10(-5), two-sided chi-square test). Of 5 psoriasis patients tested for HCV, none were HCV antibody positive (P = .0002, two-sided Fisher's exact test). For geographic comparison, meta-analysis of the literature demonstrated a varying regional prevalence of HCV in PCT patients as follows: Northern Europe 17%, Australia/New Zealand 20%, and Southern Europe 65%. CONCLUSION: Although a marked geographic variation was found in the worldwide prevalence of HCV in PCT patients, a very large percentage of US patients with PCT had HCV infection. Our results emphasize the need for clinicians to actively look for HCV in patients with PCT.     

Chronic urticaria is not significantly associated with hepatitis C or hepatitis G infection: a case-control study

OBJECTIVE: To study the prevalence of hepatitis C virus (HCV) and hepatitis G virus (HGV) infection in patients with chronic urticaria. DESIGN: Prospective case-control study and literature review. SETTING: Dermatology department of an academic medical center in Strasbourg, France. PATIENTS: One hundred ten consecutive patients with typical urticaria lasting longer than 2 months were seen between March 1, 1997, and August 31, 1998. None had a history of viral hepatitis. Age- and sex-matched patients (n = 110) seen in the same department and during the same period were included for controls. None of the controls had a history of urticaria, pruritic dermatosis, or hepatitis. MAIN OUTCOME MEASURES: The detection of HCV antibodies through a third-generation enzyme-linked immunosorbent assay. To detect early HCV infection without plasmatic antibodies, genomic amplification of HCV RNA was carried out in all patients using 2 different methods. Hepatitis G virus RNA was detected only by genomic amplification. All measures were planned before data collection. RESULTS: Antibodies to HCV were found in 1 patient with urticaria and in 1 of the control group (0.9% of each group). None had circulating HCV RNA, and liver function test results were within the reference range. Genomic amplification without HCV antibodies was not observed. Two patients with urticaria and 2 of the control group (1.8% of each group) had circulating HGV RNA, but they had neither coinfection with HCV nor changes in their liver function test results. CONCLUSIONS: Systematic HCV screening in patients with chronic urticaria is not cost-effective, at least in Europe, because hepatitis C rates were similar to those of the general population. We could not confirm the hypothesis that urticaria occurs in an early phase of HCV infection-ie, before evidence of HCV can be detected by serologic testing. Hepatitis C virus is unlikely to be the cause of urticaria in the infected patient detected in this study because of the absence of HCV RNA and changes on liver function tests. Hepatitis G virus is also unlikely to be a cause of urticaria, as the rate of HGV positivity in this study was even lower than that in the general French population.     

Porphyrin metabolism in hepatitis C infection

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.     

Hepcidin and HFE protein: Iron metabolism as a target for the anemia of chronic kidney disease

The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines, resulting in the upregulation of the iron hormone hepcidin, also increased by iron therapy and reduced glomerular filtration, with consequent reduction in iron absorption, recycling, and availability to the erythron. This response proves advantageous in the short-term to restrain iron availability to pathogens, but ultimately leads to severe anemia, and impairs the response to erythropoietin (Epo) and iron. Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores, thereby resulting in inadequate inhibition of the activity of Ferroportin-1, inappropriately high iron absorption and recycling, and iron overload. However, in hemodialysis patients, carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation, thereby improving iron availability to erythropoiesis, anemia control, the response to Epo, and possibly survival. Therefore, anti-hepcidin therapies may improve anemia management in hemodialysis. However, HFE mutations directly favor hemoglobinization independently of hepcidin, and reduce macrophages activation in response to inflammation, whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis, so that direct inhibition of HFE-mediated regulation of iron metabolism may represent a valuable alternative therapeutic target. Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies.     

Hepatitis C and the skin

Hepatitis C is an important and common cause of chronic hepatitis and cirrhosis. Cutaneous manifestations are often the first signs of infection. Dermatologists must be aware of these manifestations, because early diagnosis is the best treatment. HCV Ab by ELISA should be ordered in patients with LCV-urticarial vasculitis, cryoglobulinemia, lichen planus, Sj?gren's syndrome, unexplained pruritus, PCT, PAN, chronic urticaria, patients starting methotrexate, unexplained pruritus, and any patient initiating therapy with a potentially hepatotoxic drug.     

Update on enzyme and molecular defects in porphyria

Each porphyria results from decreased activity of one of the enzymes of haem biosynthesis. The molecular basis of enzyme deficiencies in acute intermittent porphyria (AIP), variegate porphyria (VP) and congenital erythropoietic porphyria (CEP) is outlined. All three conditions show extensive allelic heterogeneity. In the autosomal dominant disorders, AIP and VP, no genotype/phenotype correlations have been demonstrated, and the explanation for their low clinical penetrance remains uncertain. In AIP and VP, mutational analysis is superior to biochemical methods for screening families for latent porphyria. In the autosomal recessive condition, CEP, there is some genotype/phenotype correlation — one common mutation (C73R) being associated with severe disease in homozygotes. Porphyria cutanea tarda (PCT) is not a simple monogenic disorder. Patients appear to have an inherited susceptibility to inactivation of hepatic uroporphyrinogen decarboxylase (UROD) as part of a response to hepatocyte injury by alcohol, HCV and other agents. Inherited factors that, in combination, may predispose to PCT include mutations in the UROD gene, present in about 20% of patients, and the C282Y mutation in the haemochromatosis (HFE) gene.     

Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis

Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may he attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean ± 2 S.D: 191 ± l3.5nmol/L) were significantly higher than those of a normal population (n=40; mean ± 2S.D.: 5.5 ±3.2nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may nor, however, lie explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.     

Relationship between Porphyria Cutanea Tarda (PCT) and Viral Hepatitis

Recent reports have revealed the high prevalence of serological markers of viral hepatitis in porphyria cutanea tarda (PCT). We present two cases of PCT associated with hepatitis C and discuss the relationship between PCT and viral hepatitis. Case 1: A 50-year-old Japanese male noticed blisters, erosions, and fragility on sun-exposed areas of his skin in November of 1990. He had no history of excessive alcohol intake. He had been taking analgesics for eighteen years. Case 2: A 64-year-old Japanese male was referred in October of 1989 because of pigmentation on sun-exposed areas of his skin. He had been drinking alcohol excessively for 43 years. The hepatitis C virus (HCV) antibody was present in each case. Tests for the HCV antibody and hepatitis B serological markers were run in 5 other patients. HCV antibody was present in 3 of them. The two cases negative for the HCV antibody exhibited the hepatitis B antibody. We speculated that viral hepatitis infection may play an important role in precipitating PCT in cases with a history of a long term excessive intake of alcohol or chemicals.     

Sexual transmission of hepatitis C virus infection

BACKGROUND: Hepatitis C virus (HCV) is the cause of almost all cases of parenterally transmitted non-A, non-B viral hepatitis (NANBH). HCV is an RNA virus, unrelated to the hepatitis viruses, A, B, D, or E; it was first identified in 1989. Although most infections become chronic, and it may lead to chronic liver disease, most patients with HCV infection are asymptomatic. The predominant modes of transmission are by blood, blood products, or other parenteral exposure, particularly injecting drug use. More contentious is the role of sexual transmission, although evidence for this was provided by studies of NANBH. OBJECTIVE: This review considers the evidence for sexual transmission, and the types of studies used to estimate the rate of transmission and the factors that may influence it. METHOD: A Medline search using the keywords hepatitis C, sex, transmission, and prevalence in MeSH and free text. References in papers were searched, and some unpublished data identified. References were further selected to illustrate different methodologies. FINDINGS: Evidence for sexual transmission is provided by several types of study including prevalence studies in groups at risk of other STDs, investigation of cases identified from surveillance reports, and cross sectional and longitudinal partner studies. Many studies are limited by their small size, the sensitivity and specificity of early assays, lack of controls, or the difficulty of excluding other routes of transmission. One prospective cohort study reported an incidence of 12 per 1000 person years in the sexual partners of HCV infected patients. 1-3% of partners of HCV infected patients are found to be infected in cross sectional studies. Co-infection with HIV, duration of the relationship, or chronic liver disease may be independent cofactors increasing the risk of transmission. A meta-analysis of selected studies may be informative, and further larger prospective studies are required. There is a small but definite risk of sexual transmission of hepatitis C.     

Lichen planus and hepatitis C virus infection

BACKGROUND: The association of lichen planus (LP) with liver diseases is well established. The reported prevalence rates of hepatitis C virus (HCV) antibodies in patients with LP tend to appear quite variable. OBJECTIVE: The aim of this study was to assess the prevalence of HCV antibodies in a group of patients with LP and evaluate the clinical characteristics of the subgroup with LP associated with HCV. METHODS: We studied 101 patients, 57 (56.4%) women and 44 (43.5%) men with a mean age of 48 years, consecutively diagnosed with cutaneous and/or mucosal LP between January 1992 and December 2000. We used 99 age- and sex-matched controls. RESULTS: Anti-HCV antibodies were detected in nine cases (8.9%) of the LP group but only two (2.02%) of the controls. The odds ratio between the subjects with HCV positivity and those with negative HCV virus was 4.74, with a confidence interval at 95%, between 0.999 and 22.545. A statistically significant association was only demonstrated between erosive LP and infection by HCV. CONCLUSIONS: The possibility of liver disease caused by HCV should be ruled out in patients with LP, especially in the erosive form.