Table 1.

Summary of the numbers of patients with significant elevations in liver enzyme concentration (≥3 × ULN, ≥5 × ULN and ≥10 × ULN) by treatment arm

	Standard arm (2EHRZ/4HR)	Isoniazid arm (2MHRZ/2MHR)	Ethambutol arm (2EMRZ/2MR)	p value
n 1	634	649	634
Median peak ALT as × ULN (IQR)	0.83 (0.56–1.35)	0.78 (0.53–1.23)	0.73 (0.51–1.09)	0.0465 0.0006
Median time to peak ALT in arm (days)	28 (14–84)	28 (14–84)	55 (14–84)	0.9725 0.0176
Median time to peak ALT (days) if ≥3 × ULN	28 (14–56)	18 (14–56)	28 (27–56)	0.7555 0.6056
Median time to ALT < 1 × ULN2 (days)	26 (15–42)	28 (19–42)	39 (30–61)	0.5605 0.2706
No with peak ALT ≥ 3 × ULN and < 5 × ULN (%n3)	21 (3.3%)	17 (2.6%)	11 (1.7%)	0.2047
Bilirubin > 2 × ULN	2 (0.3%)	4 (0.6%)	0 (0.0%)	0.1427
INR4 >1.5	0 (0.0%)	3 (0.5%)	1 (0.2%)	0.0987
No with peak ALT ≥ 5 × ULN and < 10 × ULN (%n3)	13 (2.0%)	16 (2.4%)	11 (1.7%)	0.6567
Bilirubin > 2 × ULN	1 (0.2%)	2 (0.3%)	1 (0.2%)	0.7927
INR4 >1.5	0 (0.0%)	0 (0.0%)	0 (0.0%)
No with peak ALT ≥10 × ULN (%n3)	7 (1.1%)	2 (0.3%)	3 (0.5%)	0.1647
Bilirubin > 2 × ULN	2 (0.3%)	0 (0.0%)	1 (0.2%)	0.3607
INR4 >1.5	0 (0.0%)	0 (0.0%)	0 (0.0%)
No of liver-related withdrawals	11 (1.7%)	7 (1.1%)	4 (0.6%)	0.178

Median days from the start of treatment to reach individual patient peak concentrations and the number of patients withdrawing from treatment for liver-related reasons are reported

ALT alanine aminotransferase, INR international normalised ratio, IQR interquartile range, ULN upper limit of normal

¹ Some patients not included due to missing ALT results

² If peak value ≥3 × ULN

³%n refers to percentage of total patients in the treatment arm

⁴ Patients with known anti-coagulant use were excluded from INR numbers

⁵ Isoniazid arm against standard therapy

⁶ Ethambutol arm against standard therapy

⁷ Chi-squared test (Fisher’s exact if any n ≤ 5)