Iron, hepatic stellate cells and fibrosis in chronic hepatitis C.

BACKGROUND/AIMS: In patients with chronic hepatitis C, hepatic iron concentration correlates with liver fibrosis. However, it is not clear whether this correlation merely reflects the presence of more active disease, or iron exacerbates chronic hepatitis C virus (HCV)-induced damage through activation of hepatic stellate cells and regeneration of hepatocytes. MATERIALS AND METHODS: We studied 72 HCV-positive patients, staged according to the Ishak's score system. We measured hepatic iron concentration with spectrophotometry and evaluated the number of hepatic stellate cells (using monoclonal antibody against alpha smooth muscle actin) and proliferating hepatocytes (using monoclonal antibody against Ki67). Iron and ferritin serum levels were also determined. RESULTS: Hepatic iron concentration correlated statistically with ferritin serum level (r = 0.59, P < 0.001), with grading (r = 0.47, P < 0.001) and staging (r = 0.51, P < 0.001) scores for chronic hepatitis in the whole group of patients. Hepatic iron concentration correlated positively with stellate cell number (r = 0.55, P = 0.004) and Ki67-positive hepatocyte number (r = 0.36, P = 0.08) in patients with chronic hepatitis C and low grading score (< 3). CONCLUSIONS: In patients with chronic hepatitis C and low grading score, hepatic iron could play a role in the activation of hepatic stellate cells and in the progression of fibrosis.

Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms.

Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to flutamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism of flutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing flutamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of flutamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with flutamide, this does not completely rule out the possibility of an immunological involvement in flutamide hepatotoxicity. The possibility of severe flutamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.

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.

[Post-infantile giant cell hepatitis. Clinical and histological response to immunosuppressive therapy]. / Epatite giganto cellulare post-infantile. Risposta clinica ed istologica alla terapia immunosoppressiva.

Giant cell transformation of hepatocytes combined with variable degrees of hepatocyte necrosis and liver fibrosis is distinctly uncommon in adults. In this age group it has most often been associated with autoimmunity, drug reaction and viral infection. Prognosis is considered quite severe ranging from mild fibrosis to established cirrhosis. We report a case of giant cell hepatitis that occurred in a 30 yrs old man, who had been taking ticlopidine for 3 years. The causative role of the drug is uncertain because aminotransferase did not fall after withdrawal. The patient fulfilled most of the criteria for a diagnosis of autoimmune hepatitis and was treated accordingly with prednisolone and azathioprine. Immunosuppressive therapy led to a clinical, biochemical and histological response.