Efficacy and safety evaluation of branched-chain amino acids’ infusion form it the liver cirrhosis
Aim of the study: branched-chain amino acids’ (BCAA) efficacy and safety evaluation in intravenous infusion form (registered drug «Hepavil») at the post-marketing application for liver cirrhosis (LC) treatment. Materials and methods. Continuous sampling method applied for the cases at which Hepavil was used, with parallel continuous sampling of cases with chronic liver disease, in which other drugs were used, but no amino acids, followed by random sampling of the groups for analysis. Study protocol (program) was approved by the ethical committee. Data statistical processing was carried out using the software packages Statistica 6.1 (series 1203d), WinPepi, NCSS 2004. Results. There was a significant difference in the blood albumin levels in the liver cirrhosis group (LC) (N = 143): mean - 27.7 g/l (95% CI = 26.7-28.7), median - 28 (95% CI = 26-29 ) before treatment and an average of 35.1 g/l (95% CI = 34.1-36.1), median (Me) 36 (95% CI = 34-38) after treatment. OR increase in the proportion of patients with a blood albumin level of 35 g/l and more before / after the BCAA infusion therapy course is 8.28 at 95% CI = 4.44-15.42. The NNT was 2.2 (95% CI = 2.0-3.4). OR of the more frequent occurrence of blood albumin 35 g/l and higher after treatment with cirrhosis-B patients was 7.41 (95% CI = 2.9-18.7), with cirrhosis-C - 8.78 (95% CI = 3,1-24.9), with cirrhosis-C and ascites - 11.7 (95% D = 12.4-57.3), alcoholic cirrhosis-C - 14.4 (95% CI = 3.9-53.7 ), non-alcoholic cirrhosis-C - 6.67 (95% CI = 1.96-22.7). Hepavil treatment significantly reduced the patients’ incidence (in %) of a high prognostic per year mortality outcome index in patients with cirrhosis C: OR 4.5 (95% CI = 1.7-10.4) (for p = 0.012). There was a significant difference in blood platelet counts (secondary efficacy point): before treatment, mean was 146.4×109 (95% CI = 131.4-161.4), median (Me) - 123×109 (95% CI = 104-141 ) and after treatment mean was 169.4×109 (95% CI = 151.7-186.9), Me - 144×109 (95% CI = 122-165). The total incidence of mild adverse events (reactions) was 7.0% (95% CI = 3.4-12.5), the absolute risk of adverse events (reactions) was 0.07 and NNH - 13.7 (95% CI = 3,3-∞), while OR was statistically insignificant - 0.45 (95% CI = 0.1-1.7). There were no significant differences in OR of adverse events in the group of liver cirrhosis treated with BCAA in comparison with the group without treatment. Conclusion. BCAA infusions it liver cirrhosis demonstrated high efficacy on the blood albumin’s level. The NNT was 2.2 (95% CI = 2.0-3.4). Treatment with BCAA significantly reduced the patients’ with cirrhosis C incidence (in %) of a high prognostic per year mortality outcome index: OR is 4.5 (95% CI = 1.7-10.4) (for p = 0.012). Values of blood platelets before treatment were significantly lower than after treatment in patients with liver cirrhosis. The incidence of mild adverse events (reactions) according to clinical evaluation and laboratory-biochemical indicators was 7.0% (95% CI = 3.4-12.5) and NNH = 13.7 (95% CI = 3.3-∞). OR of adverse events’ development was not significantly different between LC treated groups, compared with the LC group without Hepavil treatment.