Table 4.
Clinic features of hepatic sinusoidal obstruction syndrome (HSOS) patients associated with Tu-San-Qi exposure (Part A) and contents of pyrrolizidine alkaloids (PA) and pyrrolizidine alkaloids N-oxides (PA N-oxide) in herbal samples ingested by patients (Part B).
| Part A | ||||||||
|---|---|---|---|---|---|---|---|---|
| Patient code | Liver function testa | Formulation | Duration (days) | Dosage | Blood level of pyrrole-protein adducts (nM)b | Outcome (at ~100 days after diagnosis)c | ||
| ALT (U/L) | AST (U/L) | Total bilirubin (µmol/L) | ||||||
| P1 | 37.0 | 68.0 | 26.4 | Tea | 4 | Unclear | 6.07 | Recovery |
| P2 | 61.0 | 58.0 | 129.6 | Decoction | 15 | 2000 mL | 12.90 | Death |
| P3 | 19.0 | 34.0 | 198.0 | Medicinal liquor | 730 | Unclear | 11.80 | Death |
| P4 | 20.0 | 56.0 | 38.1 | Capsule | 31 | Unclear | 15.90 | Death |
| P5 | 15.0 | 46.0 | 26.4 | Unclear | 72 | Unclear | 4.70 | Recovery |
| P6 | 1027.0 | 930.0 | 12.8 | Boiled egg with herb | 22 (take every other day) | 150 g/day | 74.40 | Liver transplant |
| P7 | 37.0 | 40.0 | 34.0 | Medicinal liquor | 7 | 15–30 mL | 11.50 | Recovery |
| P8 | 177.0 | 123.0 | 28.9 | Medicinal liquor | 121 | 100 mL/day | 0.33 | Recovery |
| P9 | 128.8 | 80.3 | 38.9 | Powder | 204 | ~2 g/day | 10.70 | Death |
| P10 | 37.0 | 71.0 | 40.8 | Decoction | 11 | 50 mL/day | 20.02 | Recovery |
| P11 | 549.0 | 395.0 | 11.7 | Medicinal liquor | 45 | 100–150 mL/day | 32.11 | Chronicity |
| P12 | 394.0 | 537.0 | 43.8 | Decoction | 10 | 60 mL/day | 0.65 | Death |
| P13 | 11.0 | 12.0 | 41.2 | Powder | 100 | Unclear | 0.14 | Recovery |
| P14 | 369.0 | 576.0 | 47.5 | Medicinal liquor | 7 | Unclear | 8.50 | Death |
| P15 | 344.0 | 237.0 | 17.6 | Unclear | 10 | Unclear | 0.14 | Chronicity |
| Part B | |||||
|---|---|---|---|---|---|
| Herb code | PA content (mg/g herb) | PA N-oxide content (mg/g herb) | Total PA + PA N-oxide contents (mg/g herb) (% of PA N-oxide)b | ||
| Senecionine | Seneciphylline | Senecionine N-oxide | Seneciphylline N-oxide | ||
| GJ1 | 0.109 ± 0.002 | 0.132 ± 0.003 | 0.029 ± 0.000 | 0.004 ± 0.000 | 0.274 ± 0.005 (12.0%) |
| GJ2 | ND | ND | 0.484 ± 0.064 | 0.345 ± 0.041 | 0.829 ± 0.105 (100.0%) |
| GJ3 | 0.076 ± 0.005 | 0.145 ± 0.003 | 4.198 ± 0.447 | 3.467 ± 0.212 | 7.886 ± 0.656 (97.2%) |
| GJ4 | 0.056 ± 0.007 | 0.239 ± 0.027 | 0.810 ± 0.102 | 1.179 ± 0.142 | 2.283 ± 0.268 (87.1%) |
| GJ5 | 0.029 ± 0.003 | 0.055 ± 0.004 | 4.597 ± 0.581 | 2.772 ± 0.462 | 7.452 ± 1.049 (98.9%) |
| GJ6 | 0.011 ± 0.002 | 0.032 ± 0.009 | 6.993 ± 1.257 | 5.729 ± 1.095 | 12.765 ± 2.313 (99.7%) |
| GJ7 | ND | ND | 0.380 ± 0.121 | 0.174 ± 0.077 | 0.554 ± 0.197 (100.0%) |
| GJ8 | ND | ND | 6.980 ± 0.377 | 1.208 ± 0.087 | 8.188 ± 0.460 (100.0%) |
| GJ9 | ND | ND | 1.277 ± 0.352 | 2.960 ± 0.446 | 4.237 ± 0.790 (100.0%) |
| GJ10 | 0.324 ± 0.006 | 0.442 ± 0.008 | 3.032 ± 0.053 | 1.948 ± 0.020 | 5.746 ± 0.077 (86.7%) |
| GJ11 | 0.018 ± 0.000 | 0.015 ± 0.000 | 9.206 ± 0.060 | 0.855 ± 0.016 | 1.828 ± 0.018 (89.2%) |
| GJ12 | 0.030 ± 0.000 | 0.024 ± 0.000 | 10.615 ± 0.057 | 2.977 ± 0.010 | 10.094 ± 0.051 (99.7%) |
| GJ13 | 0.070 ± 0.001 | 0.128 ± 0.001 | 0.882 ± 0.011 | 0.748 ± 0.006 | 13.645 ± 0.059 (99.6%) |
| GJ14 | ND | ND | 2.999 ± 0.525 | 3.240 ± 0.483 | 6.240 ± 1.004 (100.0%) |
| GJ15 | 0.709 ± 0.040 | 0.690 ± 0.039 | 4.006 ± 0.197 | 6.040 ± 0.251 | 11.445 ± 0.524 (87.8%) |
Herb codes (GJ1-15) in Part B correspond to the patient codes (P1-15) in Part A, respectively.
ND not detectable.
aALT normal reference range: <40 U/L; AST normal reference range: <35 U/L; total bilirubin normal reference range: 5–28 µmol/L.
bBlood level of pyrrole-protein adducts and the total contents of PA + PA N-oxide of GJ1-15 were reported by our group [20].
cClinical outcome was classified into recovery (signs and symptoms disappeared and drug therapies were stopped at 100 days after the onset), chronicity (signs and symptoms remained for 100 days and therapeutic drugs, such as diuretics, were needed), and severe outcome (liver injury caused the death or liver transplantation was performed within 100 days after the onset).