Are Haemochromatosis Mutations Related to the Severity of Liver Disease in Hepatitis C Virus Infection?

Abstract

It has been proposed that iron overload may adversely affect liver disease outcome. The recent identification of 2 mutations in the HFE gene related to hereditary haemochromatosis (Cys282Tyr and His63Asp) provided an opportunity to test whether they are associated with hepatic iron accumulation and the activity and severity of liver disease in hepatitis C virus (HCV) infection. We investigated the prevalence of HFE mutations in 135 male patients with chronic HCV hepatitis, and correlated genotype distribution with different parameters of iron status and the activity and severity of liver disease. Of these 135 patients, 6 (4.4%) carried Cys282Tyr and 32 (23.7%) carried His63Asp, frequencies which were similar to those observed in healthy controls. Serum iron levels and transferrin saturation (but not ferritin levels or liver iron content) were significantly higher in carriers than in non-carriers of HFE mutations. No difference was observed in serum ALT, AST and GGT levels between carriers and non-carriers. Finally, scores for necroinflammatory activity and fibrosis in the liver were significantly higher in HFE carriers than in non-carriers. Patients with chronic HCV infection carrying HFE mutations tend to present more evident body iron accumulation and a higher degree of necroinflammatory activity and fibrosis in the liver. HFE gene mutations might be an additional factor to be considered among those implicated in the determination of a worse prognosis of the liver disease in chronic HCV infection.

Prevalence of C282Y and H63D mutations in the HFE gene of Brazilian individuals with clinical suspicion of hereditary hemochromatosis

“…The frequencies of C282Y and H63D mutations found in this study are greater than those reported for the general Brazilian population, 1,8,11,13,15,[17][18][19][20][21][22] but are smaller than the genotypic frequencies among patients with HH. 2,3,4 It is unquestionable that C282Y is the main mutation responsible for HH in all studied populations, as the majority of published reports worldwide cite its prevalence in more than 80% of individuals with clinical manifestations of HH, 1,[4][5][6]12,15,17,23 thus several other diagnostic guides are based on the result of C282Y mutation genic testing.…”

Hemochromatosis Gene Mutations: Prevalence and Effects on Pegylated-Interferon and Ribavirin Therapy Response in Chronic Hepatitis C in Sardinia

“…10 These observations indicate the important role of iron in the pathogenesis of CHC. In fact patients with combined hereditary hemochromatosis and chronic hepatitis C infection presented advanced fibrosis/cirrhosis at a younger age and at a lower hepatic iron concentration compared to HH patients.…”

“…Overall, only a few studies have suggested an increased prevalence of HFE mutations in CHC patients, 8,9 with respect to the general population; this observation was not confirmed in other studies. 10 Laboratory abnormalities of iron metabolism have been detected in 15-20% of heterozygotes, but heterozygosity for hemochromatosis is rarely associated with liver damage due only to iron overload. Complications have been recognized only when other disorders, such as porphyria cutanea tarda, chronic anemia, alcoholism and hepatitis are also present.…”

Host genetic determinants in hepatitis C virus infection

“…119 Given the observation that a number of individuals with chronic HCV infection have excess hepatic iron, 120 some investigators have examined whether possession of these variants is associated with advanced liver disease. The results of these studies have been discrepant, 119,121 with four studies suggesting an association between possession of HFE variants and increased fibrosis or cirrhosis, 80,92,101,109 and the other studies suggesting that there are no associations. Methodological differences may account for these differing observations.…”

“…80,92,93,97,98,102,109,111,101 Two major polymorphisms are recognised in the literature: Cys282Tyr and His63Asp (often abbreviated as C282Y and H63D, respectively, in single-letter amino-acid notation). Of these two polymorphisms, the Cys282Tyr has been of greater interest.…”