Table 2.
Outcome hepatotoxicity, only those with ALT <1,000 U/L on presentation
| Metabolites/Biomarker with initial acetaminophen concentration | No hepatotoxicity (median) (IQR, [range]) (n) (n = 174) | Hepatotoxicity (median) (IQR, [range]) (n) (n = 25) | Difference between medians (95% CI) | P value |
|---|---|---|---|---|
|
APAP‐hospital lab (μmol/L) |
702 (292–1,351, [3–5,614]) (n = 174) |
1,106 (528–1,969, [33–3,423]) (n = 25) |
404 (−25 to 655) | NS |
|
ALT (U/L) |
19 (14–28, [5–276]) (n = 172) |
127 (49–221, [18–726]) (n = 25) |
108 (53 to 141) | <0.0001 |
| Acetaminophen ratio |
1.1 (0.4–2.1, [0.0–10.3]) (n = 174) |
3.6 (2.3–7.8, [0.3–27.6]) (n = 25) |
2.5 (1.8 to 3.9) | <0.0001 |
| Acetaminophen metabolite | ||||
|
APAP‐LC/MS (μmol/L) |
675 (291–1,196, [8–4,634]) (n = 174) |
867 (402–1,460, [10–4,800] (n = 25) |
192 (–123 to 464) | NS |
|
APAP‐Glu (μmol/L) |
479 (299–841, [16–3,529] (n = 174) |
568 (409–1,041, [13–3,605] (n = 25) |
89 (–55 to 264) | NS |
|
APAP‐Sul (μmol/L) |
79 (54–116, [10–350]) (n = 174) |
49 (25–72, [5–264]) (n = 25) |
–30 (–48 to [–15]) | 0.0002 |
|
APAP‐Cys (μmol/L) |
9.7 (6.2–16.8, [0.0–43.6]) (n = 174) |
34.8 (25.6–47.8, [1.4–112.6]) (n = 25) |
25.1 (18.5 to 29.8) | <0.0001 |
|
APAP‐Mer (μmol/L) |
1.2 (0.6–2.2, [0.03–16.32] (n = 174) |
2.3 (1.1–4.0, [0.07–23.8]) (n = 25) |
1.1 (0.29 to 1.5) | 0.003 |
|
CYP total (μmol/L) |
10.8 (6.9–19.5, [0.3–57.0]) (n = 174) |
36.8 (27.8–51.7, [1.4–136.4]) (n = 25) |
26.1 (19.1 to 31.6) | <0.0001 |
| Total metabolites |
589 (382–979, [27–3,862]) (n = 174) |
654 (459–1,179, [19–3,845]) (n = 25) |
64 (–79 to 262) | NS |
| % APAP‐Glu |
85 (77–89, [23–95]) (n = 174) |
89 (82–90, [67–94]) (n = 25) |
3.9 (–0.09 to 5.7) | NS |
| % APAP‐Sul |
13.1 (9.1–20.8, [2.8–67]) (n = 174) |
6.3 (4.6–10.9, [2.7–24.7]) (n = 25) |
–6.8 (–8.7 to [–3.4]) | <0.0001 |
| % CYP metabolites |
1.7 (1.3–2.6, [0.1–18.2]) (n = 174) |
5.4 (3.8–7.7, [1.1–14.5]) (n = 25) |
3.7 (2.7 to 4.3) | <0.0001 |
| Proposed risk stratification tools | ||||
| APAP‐Cys/APAP‐ Sul |
0.12 (0.06–0.21, [0.0–1.7]) (n = 174) |
0.83 (0.44–1.08, [0.1–2.2]) (n = 25) |
0.7 (0.5 to 0.8) | <0.0001 |
| ALT * APAP‐Cys/APAP‐Sul |
2.2 (1.1–4.5, [0.0–75.6]) (n = 172) |
116 (23.7–212, [1.9–997]) (n = 25) |
114 (86 to 144) | <0.0001 |
| Acetaminophen ratio*APAP‐Cys |
10 (2–27, [0.0–352]) (n = 174) |
118 (33–289, [2–2,370]) (n = 25) |
108 (75 to 178) | <0.0001 |
| Acetaminophen ratio*APAP‐Cys*ALT |
186 (50–528, [0.0–12,194]) (n = 172) |
15,543 (1,887–66,184, [509–378,805]) (n = 25) |
15,357 (6,267 to 18,878) | <0.0001 |
NS, not significant.