Silybin and the liver: From basic research to clinical practice

Table 9 Main studies performed by using purified silybin as drug

Authors	Type of study, number of patients	Drug used, dose and duration of treatments	Outcomes	Results	Clinical relevance
Vailati et al[146]	A phase II randomised, open trial on 60 patients with chronic alcoholic or viral hepatitis	Three doses (160, 240, 360 mg) of silybin and phosphatidylcholine (IdB 1016, Indena, Italy) for two weeks. No placebo or no intervention group was used	Liver tests	Improvement of liver enzymes with all used doses	Scarce
Buzzelli et al[147]	Double blind with identical placebo. Twenty patients with HBV and/or HCV chronic active hepatitis	IdB1016 (complex with phosphatidylcholine and silybin) two capsules, twice a day (equivalent to 120 mg of silybin in each capsule) (480 mg/d). Duration of treatment and of follow-up: two months in total	Mortality. Liver biochemistry	Improvement of liver enzymes and bilirubin	Scarce
Buzzelli et al[148]	Unclear, described as double blind but the method to achieve this was not described. Trial characteristics: cross over design. Patients were assigned to the Silipide group for two months treatment, and one month washout. Ten patients with chronic hepatitis C. (non-responders) to a previous treatment with recombinant interferon α	Silipide (IdB1016) capsules 360 mg/d. Control group: placebo capsules. Duration of treatment and follow-up: two months of treatment and one month of washout	Mortality. Liver biochemistry	Results were not reported separately, only overall results. Improvement of liver tests	Data published only in abstract form
Lirussi et al[104]	Blinding: adequate, double blind with placebo of identical appearance. Sixty out-patients with chronic alcoholic liver disease and non-insulin dependent type 2 diabetes	Silybin-β-cyclodextrin (135 mg silybin) sachets t.i.d Duration of treatment: 6 mo	Mortality. Liver biochemistry	Decrease of fasting glucose and lipid peroxidation markers	Good
Bares et al[138]	Randomized study to 1 of 3 oral doses. Thirthy seven patients with chronic hepatitis C non responders to a previous IFN treatment	IdB1016 at 314, 628, 942 mg t.i.d.(120,240 and 360 mg t.i.d. silybin equivalents, respectively) for 12 wk	Effects on serum markers of iron status	There was a significant decrease in serum ferritin, that was independently associated with the stage III-IV of liver fibrosi	Good
Falasca et al[134]	Observational study on forthy naïve HCV positive patients (30 treated and 10 observed without treatments)	Silybin-Vitamine E-Phospholipid Complex (Realsil®- Ibi-Lorenzini-Italy) in a dose of 4 pills per day (each pill: 47 mg of silybin) for 3 mo	Hepatoprotection and anti-inflammatory effect by determining cytokine pattern and markers of liver disease	Improvement of liver enzymes and of Il2 plasma levels. Improvement of insulin resistance markers in patients with contemporaneous liver steatosis	Medium
Federico et al[141]	Observational study on 85 outpatients: 59 with NAFLD and 26 with HCV related chronic hepatitis in combination with NAFLD, non-responders to previous antiviral treatment. 53 (39 NAFLD and 14 HCV) were treated, while the other 32 patients (20 NAFLD and 12 HCV) served as a control group (no treatment)	The complex silybin-vitamin E-phospholipids (Realsil®), 4 pieces/d for six months followed by another six months of follow up	Effects on insulin resistance and liver damage	US steatosis, liver enzymes, hyperinsulinaemia, and indices of liver fibrosis were improved in both treated groups	Suggestive
Ferenci et al[139]	Observational study on 36 patients with HCV chronic hepatitis non responders to IFN + ribavirin. Duration of the study: 7 d	Silybin i.v. (Madaus, Germany) at 5, 10, 15 and 20 mg/kg per day for 14 d	Effect on viral load. Safety	Good compliance, no side effects and potent antiviral effect against HCV	High