Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection

Abstract

The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

Hepatic Injury Correlates With Apoptosis, Regeneration, and Nitric Oxide Synthase Expression in Canine Chronic Liver Disease

“…There is also increased iron accumulation in all compartments of the liver, similar to what has been reported in various human chronic liver diseases 50,59 and suggested to be a result of the phagocytosis of dead cells, particularly hepatocytes, with local concentration of iron storage products for which there is no excretory mechanism. 12 There was no significant correlation between hepatocyte immunoreactive MDAprotein adduct score and presence and severity of liver injury and inflammation, an unexpected finding that is in contrast to the findings of Spee et al, 60 who found that dogs with chronic inflammatory and cholestatic liver diseases tended to have reduced GSH:GSSG ratios (an alternate indirect indicator of oxidative stress).…”

“…32 Similarly, the transitional metal ion iron is associated with chronic liver disease as a result of primary iron overload in hereditary hemochromatosis in humans 46 but also accumulates in chronic liver disease associated with hepatitis C virus 59 and alcohol-related liver disease. 50 The effects of nitric oxide (NO) on hepatocytes are complex and dependent on physiologic context; by itself, NO has been demonstrated to be antiapoptotic for hepatocytes, 11,25,[33][34][35]38,63 but with concurrent oxidative stress, NO potentiates hepatocellular necrosis through the evolution of peroxynitrite, a highly reactive oxygen species that can damage a broad variety of organic molecules producing nitrotyrosine-protein adducts.…”

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

“…However, the absence of SVR observed in the group of individuals with this genetic marker was probably not directly related to iron overload, since most studies, so far, failed to report a significant difference in hepatic iron concentration between HCV patients with or without SVR after IFN/RBV treatment (23,25,29,33) . Moreover, therapeutic phlebotomies generally did not increase SVR, indicating that reduction of body iron stores was not associated with treatment outcome (11,21) .…”

Hepcidin Expression in the Liver: Relatively Low Level in Patients with Chronic Hepatitis C

“…Increased hepatic iron concentration is present in 10% to 36% of patients with chronic hepatitis C (8,9), and hepatic iron overload is even more common among patients with end-stage liver disease due to hepatitis C (10,11). Excess iron deposition in the liver is known to be hepatotoxic and may exacerbate liver injury (12) and be resistant to interferonbased therapy in patients with chronic hepatitis C (13,14); however, little is known about the mechanism of iron accumulation in the liver. We previously reported that transferrin receptor 2 (TfR2), which was recently identified as the second receptor for transferrin (15), was higher in the liver of patients with chronic hepatitis C compared than those with chronic hepatitis B (16).…”