Levels of circulating endothelin-1 and nitrates/nitrites in patients with virus-related hepatocellular carcinoma

A balance between endothelins (ET) and nitric oxide (NO) might interfere wi th liver haemodynamics and disease progression in various liver diseases. I ncreased levels of endothelin 1 (ET-1) and nitrites and nitrates (NOx, the end products of NO metabolism) have been reported in hepatocellular carcino ma (HCC), but the balance has not been studied. The purpose of this study w as to assess the ratio of NOx to ET-1 in patients with virus-related hepato cellular carcinoma and to investigate its correlation with the extent of th e disease. Eighteen patients with virus-related HCC (six Okuda stage I, six Okuda stage II and six Okuda stage III) were included in the study and wer e compared with 22 patients with viral cirrhosis (14 decompensated, eight c ompensated) and seven normal controls. ET-1 was measured with an ELISA assa y and NOx with a modification of the Griess reaction. Patients with virus-r elated HCC had the highest levels of circulating ET-1 and NOx (13.24 +/- 0. 82 pg/ml and 112.28 +/- 18.56 mu mol/l) compared to compensated cirrhosis ( 9.47 +/- 0.50 pg/ml, P < 0.004 and 54.47 +/- 2.36 mu mol/l, P < 0.01), deco mpensated cirrhosis (9.57 +/- 0.32 pg/ml, P < 0.001 and 90.20 +/- 11.23 mu mol/l, NS) and normal controls (8.84 +/- 0.61 pg/ml, P < 0.001 and 51.17 +/ - 6.18 mu mol/l, P < 0.01). There was a significant increase of ET-1 and NO x at HCC stage III compared to HCC stages I and II, cirhotics and controls. HCC stage III patients also had a NOx/ET-1 ratio that was higher than HCC stages I and II patients, normal controls and patients with compensated cir rhosis. Virus-related HCC patients have high levels of circulating ET-1, co mpared to compensated or decompensated cirrhosis. Highest levels of ET-1 ar e produced in Okuda III tumours. NOx are also increased but only in Okuda s tage III tumours. The NOx/ET-1 ratio is increased in virus-related HCC and DC. This increase may account for the known increase in tumour blood flow.