Hepatic iron overload in patients with chronic viral hepatitis: Role of HFE gene mutations

Abstract

Mild to moderate hepatic iron overload is frequent in patients with chronic viral hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and other acquired factors in the development of iron overload in these patients. We studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men), including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by semiquantitative analysis in all the patients, and hepatic iron concentration (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations were sought in all the subjects by a polymerase chain reactionrestriction assay. The frequency of HFE genotypes and alleles did not differ in patients and controls. No relation was detected between hepatic iron stores and HFE gene mutations in women. In men, all C282Y heterozygotes had iron overload, and the H63D mutation was significantly more frequent in patients with more marked hepatic siderosis than in those with mild or no siderosis (P ‫؍‬ .0039) and in controls (P ‫؍‬ .0008). Heavy alcohol intake and hepatic cirrhosis were also associated with increased hepatic iron stores in the men. In the 71 men in whom HIC was measured, multiple regression analysis showed that this variable was related independently only to alcohol intake and HFE gene mutations. We suggest that in patients with CH, iron accumulates in the liver as the result of an interplay between genetic and acquired factors, and that increased liver iron stores may influence progression toward liver fibrosis. (HEPATOLOGY 1998;28:1105-1109

Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C

“…The total iron score (TIS, 0 -60) was defined by the sum of these scores. This score has been shown to highly correlate with the biochemical hepatic iron index and hepatic iron concentration as measured by the atomic absorption spectrophotometry in patients with chronic liver diseases (Piperno et al, 1998;Silvia et al, 2005).…”

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

“…These parameters lack specificity, particularly in the face of chronic inflammatory conditions or alcohol-induced liver disease. 27 Previous reports suggested that TSI measurement appears to be the most sensitive method of detecting iron overload states and showed that TSI values exceeding 45% correctly identified 97.9% of homozygotes for Hereditary Hemochromatosis, with no false positives among the normal population, and 22.2% of the heterozygote population. Detecting the threshold for TSI to 45% could also identify other groups with relatively minor degrees of secondary iron overload, such as chronic hepatitis C. 33,34 Recent evidence suggests that HFE gene mutations and a consequent mild iron overload may worsen the course of chronic hepatitis C and increase the progression of fibrosis.…”

Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal

“…We identified 8 case control studies seeking an association between HFE C282Y gene mutation in patients with chronic hepatitis C and progression of fibrosis. 5,6,[110][111][112][113][114][115] Based on a threshold of P ϭ .05, only 2 of the studies showed an association between polymorphisms in the HFE gene and progression of fibrosis. Because of its prevalence and clinical interest, it is important to conduct additional well-designed studies to solve this question.…”