Efficiency and safety of silymarine in patients with chronic liver diseases – multicenter, prospective, open clinical trial IMHOTEP

Česká verzia

Authors: J. Holomáň ¹; P. Borecký ²; J. Lietava ³
Authors place of work: Národné referenčné centrum pre liečbu chronických hepatitíd, SZU v Bratislave ¹; ŠGN Podunajské Biskupice, UN Bratislava ²; II. interná klinika LFUK a UN Bratislava ³
Published in the journal: Gastroent Hepatol 2014; 68(4): 346-355
Category: Hepatology: Original Article

Summary

Silymarine is the most commonly prescribed hepatoprotective medicine in real clinical practice. The evidence from the last decades has confirmed a relationship between its efficiency and dosing. The prescribing practice is actually not always fast enough to reflect the latest findings and changes in rational pharmacotherapy.

Design:
A multicenter, prospective, open clinical study IMHOTEP in patients with chronic hepatopathy of different etiology, indicated for chronic treatment with therapeutic dosing of silymarine as chosen by the doctor during a 36-week observation. Selected markers of hepatic injury (AST, ALT, GMT, ALP, total and conjugated bilirubin) as well as the objective symptoms and patients’ subjective complaints were monitored at defined time intervals.

Population size and results:
A total of 1,069 patients were included, of which 594 (55.6%) were men with an average BMI of 29.4 kg/m² and 475 (44.4%) were women with an average BMI of 29.1 kg/m². The average age of males was significantly higher than that of women (57 ± 12 vs 50 ± 13 years) (p < 0.001). Etiologies of chronic liver disease were dominated by non-alcoholic fatty liver disease (41.3%), followed by alcohol (17.2%) and drug-induced (9.2%) etiology. Alcohol etiology was significantly more common among men (24.1 vs 8.6%; p < 0.001). Smoking was more common among men (26.7 vs 14%; p < 0.001). The average dose of silymarine in the entire population was 472 ± 131 mg/day in the initial phase of the study and 470 ± 162 mg/day at the end of the study, while in men the daily therapeutic dose (DTD) of silymarine was 20 mg higher on average. During treatment with silymarine (V0 vs V4) we recorded a statistically significant decrease in the markers of hepatic damage in ALT: 2.2 ± 1.47 µkat/L vs 0.75 ± 0.50 µkat/L (p < 0.001); AST: 1.07 ± 1.24 µkat/L vs 0.62 ± 0.37 µkat/L (p < 0.001); GMT: 2.82 ± 3.39 µkat/L vs 1.97 ± 1.52 µkat/L (p < 0.001); ALP: 1.66 ± 1.18 µkat/L vs 1.41 ± 0.68 µkat/L (p < 0.001). The total amount of bilirubin in the entire study group decreased non-significantly 15.7 ± 12.6 vs 15.3 ± 13.13 (p < 0.599), while the decline in conjugated bilirubin was statistically significant 5.7 ± 8.2 µmol/L ± 4.3 vs 3.3 µmol/L (p < 0.001). Although we did not find any statistically significant differences in the entry values or in the ALT, AST, or ALP activities changes between men and women, in men we recorded a more significant decrease of GMT, both types of bilirubin and ALP. In parallel with the decrease in laboratory markers, a statistically significant decrease in the perception of symptoms associated with chronic hepatopathy and an increase in the number of asymptomatic patients was recorded.

Conclusions:
Treatment with silymarine has confirmed its hepatoprotective effects; we noticed a significant improvement in laboratory markers, as well as in the subjective and objective manifestations of chronic hepatic injury symptoms. The average dosing of silymarine over the entire course of the study was higher in comparison with the “traditional” dosing. We confirmed the relationship between the efficiency and the dosage of the medicine. Intersexual differences in efficiency were probably due to the higher values of the hepatic injury markers and higher prevalence of alcoholic etiology of chronic hepatopathy in men. In the course of the study no serious adverse effects related to the silymarine treatment were recorded.

Key words:
chronic liver disease – hepatoprotective drugs – silymarine – intersexual differences – rational pharmacotherapy – adverse effects

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
20. 1. 2014

Accepted:
18. 5. 2014

Zdroje

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