BACKGROUND: Despite advances in the understanding of the pathophysiological basis of autoimmune hepatitis (AIH), it is still difficult to delineate the mechanisms involved in progression from hepatic inflammation toward fibrosis. Our aim was to study serum concentrations of NO in AIH of different histological severity and possible effects of immunosuppressive therapy on NO production. MATERIALS AND METHODS: We studied serum NO metabolites (NOx) in 47 consecutive patients with AIH and in 28 age- and sex-matched controls. RESULTS: Serum NOx concentrations were higher in AIH patients than in controls (10.3 (4.5-27.3 µmol/L) vs. 4.3 (1.6-14.3 µmol/L), p < 0.001). According to liver histology, median NOx concentrations were significantly higher in patients with severe interface hepatitis compared to patients with mild-moderate interface hepatitis (12.3 (4.5-27.3 µmol/L) vs. 9.3 (4.6-20.3 µmol/L), p = 0.029). Similarly, serum NOx concentrations were significantly higher in patients with advanced fibrosis than in those with early fibrosis (12.2 (4.6-27.3 µmol/L) vs. 9.3 (6.6-12.8 µmol/L), p = 0.018). NOx concentrations decreased in 16 AIH patients who were tested also after biochemical remission was achieved (12.6 (4.5-22.8 µmol/L) at baseline and 5.9 (2.8-10.5 µmol/L) after remission, p = 0.001). CONCLUSION: This study shows that serum NOx levels are associated with the histological severity of AIH. Hepatocyte inflammation and injury may activate hepatic stellate cells and kupffer cells, and the consequences may include release of NO, which ultimately promotes hepatic fibrosis. Immunosuppressive therapy inhibits this process and the production of NO.
BACKGROUND: Despite advances in the understanding of the pathophysiological basis of autoimmune hepatitis (AIH), it is still difficult to delineate the mechanisms involved in progression from hepatic inflammation toward fibrosis. Our aim was to study serum concentrations of NO in AIH of different histological severity and possible effects of immunosuppressive therapy on NO production. MATERIALS AND METHODS: We studied serum NO metabolites (NOx) in 47 consecutive patients with AIH and in 28 age- and sex-matched controls. RESULTS: Serum NOx concentrations were higher in AIH patients than in controls (10.3 (4.5-27.3 µmol/L) vs. 4.3 (1.6-14.3 µmol/L), p < 0.001). According to liver histology, median NOx concentrations were significantly higher in patients with severe interface hepatitis compared to patients with mild-moderate interface hepatitis (12.3 (4.5-27.3 µmol/L) vs. 9.3 (4.6-20.3 µmol/L), p = 0.029). Similarly, serum NOx concentrations were significantly higher in patients with advanced fibrosis than in those with early fibrosis (12.2 (4.6-27.3 µmol/L) vs. 9.3 (6.6-12.8 µmol/L), p = 0.018). NOx concentrations decreased in 16 AIH patients who were tested also after biochemical remission was achieved (12.6 (4.5-22.8 µmol/L) at baseline and 5.9 (2.8-10.5 µmol/L) after remission, p = 0.001). CONCLUSION: This study shows that serum NOx levels are associated with the histological severity of AIH. Hepatocyte inflammation and injury may activate hepatic stellate cells and kupffer cells, and the consequences may include release of NO, which ultimately promotes hepatic fibrosis. Immunosuppressive therapy inhibits this process and the production of NO.