Evaluation of nitrite/nitrate levels in relation to oxidative stress parameters in liver cirrhosis.

BACKGROUND AND OBJECTIVE: Nitric oxide and reactive oxygen species have been implicated in several pathophysiological events leading to fibrosis and cirrhosis. The aim of the present study was to investigate the possible contribution of peroxynitrite (formed by the interaction of nitric oxide and superoxide anion) in the pathophysiology of cirrhosis. METHODS: Twenty-six cirrhotic patients classified as Child-Pugh A, and seven as Child-Pugh B, were included in the study, and nine healthy volunteers served as controls. Levels of nitrite/nitrate (NOx), thiobarbituric acid-reactive substances (TBARS), nitrotyrosine (peroxynitrite marker), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured in blood samples. RESULTS: NOx, TBARS, CAT, SOD and GSH levels were higher in cirrhosis patients than in the controls (NOx: 0.17 ± 0.02, 0.95 ± 0.12, 1.3 ± 0.1; TBARS: 2.0 ± 0.05, 4.6 ± 0.3, 5 ± 0.3; CAT: 1.8 ± 0.1, 4 ± 0.3, 4.5 ± 0.4; SOD: 1.8 ± 0.2, 4.8 ± 0.5, 7 ± 0.4; and GSH: 1.3 ± 0.05, 3.6 ± 0.3, 4.5 ± 0.6 in controls, and Child-Pugh A and B patients, respectively). However, there were no differences in nitrotyrosine levels across these groups (controls: 11.4 ± 0.4; Child-Pugh A: 11.1 ± 0.4; Child-Pugh B: 11.9 ± 1.6). NOx levels showed significant and strongly positive correlations with TBARS, SOD, CAT and GSH levels. In contrast, no correlations were found between either NOx or TBARS and nitrotyrosine levels. CONCLUSION: Nitric oxide and reactive oxygen species, but not peroxynitrite, are overproduced in patients with cirrhosis in spite of evidence of an increase in antioxidant defenses. This suggests that therapeutic measures aimed at attenuating oxidative stress as well as increasing antioxidant defenses may well benefit patients with cirrhosis.

Liver involvement in sickle cell disease.

BACKGROUND/AIMS: Liver involvement in sickle cell disease may take place due to the primary disease itself or to secondary conditions such as iron overload, viral hepatitis and cholelithiasis. In the present study we have tried to evaluate the frequency of hepatic dysfunction and etiological factors in 48 patients with sickle cell disease. METHODS: Clinical and laboratory investigation including liver function tests, serological tests for viral hepatitis, and abdominal ultrasonography were performed in all of the patients. Additionally, liver biopsies were taken from 13 patients. RESULTS: Intrasinusoidal sickling and Kupffer cell hyperplasia were consistently seen in all of the biopsy specimens. Hepatomegaly was present in all patients, whereas liver function test abnormalities were seen in 27%. The prevalence of cholelithiasis was found as 35%. Serological tests demonstrated the presence of hepatitis B surface antigen in three, antibody to hepatitis B virus in 19 and antibody to hepatitis C virus in four of the patients. The most significant contributory finding was the presence of hemosiderosis in histological examination of liver specimens. CONCLUSION: Our data suggest that chronic liver injury in patients with sickle cell disease seems to be a multifactorial phenomenon depending mostly on overlapping factors such as iron overload and viral damage rather than primary disease itself.

Bullous pemphigoid and cholestatic hepatitis associated with Castleman's disease.

The case of a 21-yr-old woman admitted with a two-week history of icterus, fever, multiple peripheral lymphadenopathy and pruritic eruption is presented. A full evaluation including computed tomography, endoscopic retrograde cholangiography, liver, skin and lymph node biopsies and biochemical tests confirmed the diagnosis of multicentric Castleman's disease (angiofollicular lymph node hyperplasia). All symptoms improved within four weeks of commencing prednisone therapy. Castleman's disease should be considered in the differental daignosis of cholestatic hepatitis and bullous pemphigoid.