Evaluation of iron status in patients with chronic hepatitis C.

AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.

High prevalence of hepatitis C virus (HCV) genotype 2 in Italian patients with chronic liver disease.

The prevalence of different genotypes of Hepatitis C virus may vary between geographic areas and it is possible that various genotypes have different pathogenic characteristics. Therefore, 90 consecutive Italian patients anti-Hepatitis C Virus positive with a broad spectrum of chronic liver disease, have been analysed to observe prevalence of various genotypes of Hepatitis C Virus. Genotyping was performed by polymerase chain reaction with a set of nested biotinylated primers, located in 5'UTR region. Genotype 1b and genotype 2a were the most commonly encountered (respectively, 50% and 37%) whereas other genotypes were rare. The unexpected high prevalence of genotype 2a allowed direct comparison of clinical characteristics and response to therapy between patients with genotype 2a and those with 1b. Genotype 1b was more prevalent than 2a in patients over 60 years (29 vs 12) and in those with more severe liver disease (34 vs 16). In a univariate analysis, genotype 2a was associated with less severe liver disease (p = 0.02) and younger age (p = 0.018), in comparison with genotype 1b. Patients with genotype 2a responded to interferon alpha therapy better than those with 1b (p = 0.007). In a multivariate analysis, only younger age was associated with genotype 2a. Genotype 2a (in comparison with 1b) and absence of cirrhosis were independent predictors of response to interferon alpha. In conclusion, genotype 2a is playing an emerging role in younger Italian patients and seems more sensitive than 1b to interferon alpha therapy.

Assessment of interferon cardiotoxicity with quantitative radionuclide angiocardiography.

Three different types of cardiovascular sequelae attributed to interferon therapy have been reported: arrhythmia, ischaemic heart disease and cardiomyopathy. We evaluated the left ventricular ejection fraction (LVEF) during alpha interferon therapy (3 MU administered subcutaneously three times a week for 6 months) in 11 patients with chronic viral hepatitis. LVEF was within the normal range in all patients (mean value +/- SD 64.6 +/- 10.7%) before interferon was started, but decreased after 1 month of therapy (mean value +/- SD 59.7 +/- 8.3%) (P = 0.015). An LVEF reduction of more than 10% was observed in five of the 11 patients. Three months after therapy was stopped, nine of the 11 patients showed an LVEF close to the pre-treatment level (mean value +/- SD 62.1 +/- 8.3%). In our patients with chronic C hepatitis, low subcutaneous doses of interferon alpha often decreased the LVEF. It is not clear whether this finding is due to the direct effect of interferon on cardiac cells, or to the peripheral vascular effects of the drug. As LVEF reduction could be critical in patients with previously reduced myocardial contractility, our results further highlight the need for careful cardiac analysis before starting interferon therapy.

[A sustained response in chronic hepatitis C treated with interferon]. / La risposta sostenuta nella epatite cronica C trattata con interferone.

We analyzed 27 subjects with long-term response, from a group of 110 interferon treated patients with biopsy-proven chronic hepatitis and serum anti-HCV antibodies. The following variables were assessed as potential predictors: sex, age, ALT level before the therapy was started, liver structure, type of interferon, total amount of interferon. Total amount of administered interferon statistically correlated with long-term response by univariate analysis. Nevertheless upon stepwise logistic multivariate analysis none of them was independently predictive of long-term response. Additional studies would be needed in order to develop a model capable of predicting from pre-treatment features which patients are likely to have long-term response.