Non-alcoholic steatohepatitis (NASH), because of its prevalence, frequent subclinical course, possible progression to liver cirrhosis, and yet missing of standard treatment options, poses a challenge for contemporary clinician and researcher. Aim of the study: To study effects of therapy with ursodeoxycholic acid (UDCA) upon the clinical course, blood biochemistry parameters and serum markers of liver fibrogenesis in patients with NASH. Methods: Series of 17 patients (4 women and 13 men) with NASH, diagnosed by clinical/laboratory investiga- tion, ultrasonography, and/or liver biopsy, was studied prior to, and during the therapy with UDCA (3 x 250 mg/day; duration 6 months). Of the series, 13 patients were obese. Hyperlipoproteinemia was present in 16 of 17 patients. Following laboratory investigations were done prior to, and on 1 st , 3 rd , and 6 th month of the therapy with UDCA: FW, blood counts, prothrombin time (Quick); serum biochemistry: aminotransferases (ALT, AST), alkaline phosphatase (ALP), g-glutamylranspeptidase (GMT), bilirubin, albumin, total cholesterol, triglycerides, HDL-cholesterol; serum markers of liver fibrogenesis: metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), N-terminal propeptide of procollagen III (PIIINP). Abdominal ultrasonography (with semiquantitative evaluation of liver steatosis) was performed prior to, and on 3 rd and 6 th month of the treatment. Results: After the 6-month therapy with UDCA, the amelioration of ultrasonography findings, improvement of serum biochemistry (ALT, AST, ALP and GMT), and decrease of serum concentrations of PIIINP were observed in most of the patients. The changes were statistically significant for ALT, PIIINP and ultrasonography semiquantitative evaluation (p < 0.05). There was no significant change of the mean MMP-1 or TIMP-1 serum concentrations after 6 months of the UDCA treatment. In some patients, however, a shift from decreased to normal, or even increased MMP-1 serum concentrations was observed. On the other hand, the shift from increased to normal, or even decreased TIMP-1 serum concentrations after 1 and/or 3 months was noticed. The change was significant for TIMP-1 in the 3rd month of the treatment (p < 0.02). Though a weight reduction of 3–5 kg was noted in 3 patients (1 woman, 2 men), the weight loss after 6 months was not significant for the series of patients as a whole. Serum lipid parameters remained unchanged during the treatment period. The therapy with UDCA was well tolerated, no adverse effects were recorded. Conclusion: The 6-month treatment with UDCA in patients with NASH showed a favorable effect on the biochemical activity of the disease and on the ultrasonography findings of liver steatosis. The risk of liver fibrosis development and its possible modulation by medical therapy should be further evaluated in well designed long-term clinical studies.

        Key words: non-alcoholic steatohepatitis (NASH) – ursodeoxycholic acid (UDCA) – liver fibrosis – metallopro- teinase-1 (MMP-1) – tissue inhibitor of metalloproteinase-1 (TIMP-1) – N-terminal propeptide of procollagen III (PIIINP)