Table 2.
Number and percentage (%) of patients with indicators of impaired biliary excretion, hepatocellular damage and systemic effects of liver inflammation at each visit, and mean (SD) of laboratory values at each visit.
| Symptom, Sign or Test Result | Visit Number | |||||||
|---|---|---|---|---|---|---|---|---|
| Impaired biliary excretion | Baseline | 1 | 2 | 3 | 4 | 5 | 6 | P-value |
| Dark urine*, count (%) | 0.013 | |||||||
| Silymarin | 50(91) | 34(62) | 30(59) | 27(52) | 6(13) | 3(7) | 1(3) | |
| Placebo | 38(76) | 24(57) | 14(33) | 13(30) | 6(14) | 8(18) | 4(11) | |
| Jaundice*, count (%) | 0.020 | |||||||
| Silymarin | 40(73) | 40(73) | 30(59) | 33(64) | 19(42) | 7(16) | 2(5) | |
| Placebo | 31(62) | 23(54) | 21(49) | 19(44) | 18(41) | 15(34) | 4(11) | |
| Scleral icterus, count (%) | 0.043 | |||||||
| Silymarin | 54(98) | 53(96) | 44(86) | 43(83) | 31(69) | 17(40) | 5(13) | |
| Placebo | 44(88) | 39(91) | 37(86) | 33(77) | 25(57) | 23(52) | 12(33) | |
| Clay-colored stool*, count (%) | 0.69 | |||||||
| Silymarin | 23(42) | 15(27) | 8(16) | 7(14) | 2(4.4) | 1(2.3) | 0(0) | |
| Placebo | 16(32) | 10(23) | 7(16) | 5(12) | 5(11) | 2(4.5) | 0(0) | |
| Direct bilirubin >0.3 mg/dl*, count (%) | 0.18 | |||||||
| Silymarin | 53(96) | 52(94) | 47(92) | 45(88) | 35(78) | 26(60) | 4(10) | |
| Control | 44(90) | 35(81) | 33(79) | 31(72) | 33(75) | 21(48) | 6(17) | |
|
| ||||||||
|
Hepatocellular damage | ||||||||
| Abdominal pain*, count (%) | 0.34 | |||||||
| Silymarin | 36(65) | 14(25) | 7(14) | 9(17) | 8(18) | 8(19) | 3(8) | |
| Placebo | 28(56) | 10(23) | 9(21) | 7(16) | 10(23) | 8(18) | 3(8) | |
| Abdominal swelling*, count (%) | 0.10 | |||||||
| Silymarin | 17(31) | 7(13) | 4(7.8) | 2(3.8) | 3(7) | 5(12) | 4(10) | |
| Placebo | 11(22) | 6(14) | 3(7.0) | 3(7.0) | 4(9) | 5(11) | 0(0) | |
| Enlarged liver*, count (%) | 0.17 | |||||||
| Silymarin | 19(34) | 19(36) | 18(37) | 16(31) | 12(27) | 7(16) | 3(8) | |
| Placebo | 11(22) | 10(23) | 10(24) | 9(21) | 8(18) | 7(15) | 7(19) | |
| Tender liver*, count (%) | 0.65 | |||||||
| Silymarin | 10(19) | 6(11) | 4(8) | 5(10) | 7(16) | 4(9) | 1(3) | |
| Placebo | 12(24) | 10(26) | 10(24) | 7(16) | 6(14) | 4(9) | 2(6) | |
| ALT > 40 IU/L*, count (%) | 0.56 | |||||||
| Silymarin | 55(100) | 55(100) | 51(100) | 51(100) | 37(82) | 27(63) | 6(16) | |
| Placebo | 49(100) | 43(100) | 42(100) | 41(95) | 37(84) | 24(54) | 10(28) | |
| AST > 42 IU/L*, count (%) | 0.42 | |||||||
| Silymarin | 54(98) | 53(96) | 47(92) | 42(82) | 29(64) | 20(46) | 6(16) | |
| Placebo | 48(98) | 38(88) | 36(86) | 35(81) | 27(61) | 20(45) | 8(22) | |
| Indirect bilirubin> 0.7 mg/dl*, count (%) | 0.012 | |||||||
| Silymarin | 55(100) | 51(93) | 44(86) | 43(84) | 33(73) | 25(58) | 14(37) | |
| Placebo | 42(86) | 35(81) | 32(76) | 29(67) | 27(61) | 23(52) | 12(34) | |
|
| ||||||||
|
Systemic effects of liver inflammation | ||||||||
| Fever*, count (%) | 0.33 | |||||||
| Silymarin | 14(25) | 3(5) | 4(8) | 3(6) | 2(4) | 1(2) | 2(5) | |
| Placebo | 16(32) | 2(5) | 1(2) | 2(5) | 1(2) | 3(7) | 0(0) | |
| Fatigue*, count (%) | 0.060 | |||||||
| Silymarin | 48(87) | 27(49) | 21(41) | 14(27) | 11(24) | 6(14) | 2(5) | |
| Placebo | 39(78) | 19(44) | 15(35) | 15(35) | 11(25) | 11(25) | 4(11) | |
| Malaise*, count (%) | 0.045 | |||||||
| Silymarin | 46(84) | 28(51) | 19(37) | 13(25) | 10(22) | 4 (9) | 1(3) | |
| Placebo | 38(76) | 18(42) | 14(33) | 16(37) | 10(23) | 9 (20) | 4(11) | |
| Anorexia*, count (%) | 0.061 | |||||||
| Silymarin | 44(80) | 19(34) | 14(27) | 4(8) | 4(9) | 7 (16) | 1(3) | |
| Placebo | 36(72) | 14(33) | 9(21) | 6(14) | 5(11) | 8 (18) | 3(8) | |
| Nausea*, count (%) | 0.65 | |||||||
| Silymarin | 32(58) | 18(10) | 4(8) | 5(10) | 2(4) | 6 (14) | 2(5) | |
| Placebo | 32(64) | 9(21) | 8(19) | 6(14) | 3(7) | 5 (11) | 2(6) | |
| Vomiting*, count (%) | 0.68 | |||||||
| Silymarin | 21(38) | 1(2) | 0(0) | 0(0) | 1(2) | 3 (7) | 0(0) | |
| Placebo | 18(36) | 0(0) | 2(5) | 3(7) | 0(0) | 3 (7) | 1(3) | |
P-values estimated using generalized estimating equations based on a model of group, time from baseline, and their interaction with a binomial working model and robust standard errors.
*
Time fit using natural cubic spline terms of continuous days from baseline due to < 5 participants with or without symptom in at least one group during at least one visit. Otherwise, time fit using indicators for each visit. ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; SD, standard deviation