Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C.

Background/aims: Recent evidence implicates iron as a comorbid factor for development of non-hemochromatotic liver diseases. Mutations or polymorphisms in the HFE gene or the TfR1 gene may influence the accumulation of iron in the liver or other tissues or may influence chronic viral hepatitis apart from effects on iron homeostasis. The aim of this study was to assess the role of hepatic iron, HFE and TfR1 variations on development and progression of chronic hepatitis C infection.

Management of nonalcoholic steatohepatitis: an analytic review.

Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which, although usually relatively mild, may in some cause fibrosis, cirrhosis, and premature death resulting from liver failure. Its prevalence is increasing, and it is probably underestimated as a cause for cirrhosis. The need for an effective treatment is clear and urgent.

Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone.

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000.

Hemochromatosis and porphyria.

A 52-year-old man presented to his primary care physician with blisters and sores on the backs of his hands. Laboratory studies supported a diagnosis of porphyria cutanea tarda, complicated by the presence of both the C282Y and H63D mutations in the HFE gene, with susequent iron over-load. This case illustrates the need to understand the pathogenesis of porphyria cutanea tarda, particularly the role of excess iron in the overproduction of uroporphyrin.

Intestinal expression of genes involved in iron absorption in humans.

Hereditary hemochromatosis (HHC) is one of the most frequent genetic disorders in humans. In healthy individuals, absorption of iron in the intestine is tightly regulated by cells with the highest iron demand, in particular erythroid precursors. Cloning of intestinal iron transporter proteins provided new insight into mechanisms and regulation of intestinal iron absorption.

Mapping of the chick heme oxygenase-1 proximal promoter for responsiveness to metalloporphyrins.

Heme oxygenase (HO) catalyzes the rate-controlling step of physiologic heme catabolism, namely, the oxidation of the alpha-methene bridge of the macrocycle with formation of CO, Fe, and biliverdin. HO-1, the first isoform of HO to be identified, is highly inducible by a large number of physical and chemical factors. Many of these factors cause oxidative or other stresses to cells.

Benefits of chronic plasmapheresis and intravenous heme-albumin in erythropoietic protoporphyria after orthotopic liver transplantation.

Erythropoietic protoporphyria (EPP) is characterized by a deficiency of ferrochelatase the final enzyme of the heme biosynthetic pathway. Patients with EPP may overproduce protoporphyrin IX, chiefly in developing erythrocytes. In some, protoporphyrin accumulates and causes toxicity, particularly to the skin and liver.