TABLE 7.

Characteristics of the randomized controlled trials evaluating adjuvant vitamin analogue therapy

Study (reference)	Adjuvant protocol and number of patients	Patients’ baseline characteristics
		Tumour characteristics	Liver disease	Follow-up
Vitamin A analogue
Muto et al (50,51)	Study arm: oral polyprenoic acid 600 mg/day for 12 months; n=44 Control arm: the same dosage of placebo; n=45	LCSGJ stage I–III; mean tumour number 1.5 for study arm and 1.4 for control arm; mean tumour size 2.9 cm for study arm and 3.0 cm for control arm	HCV 75%	Median 38 or 62 months
Vitamin K2 analogue
Mizuta et al (52)	Study arm: oral menatetrenone 45 mg/day until recurrence; n=32 Control arm: no adjuvant therapy; n=29	LCSGJ stage I–III; mean tumour number 1.5; mean tumour size 18 mm2 for study arm and 19 mm2 for control arm; vascular invasion 0%	C-P A 79%; HCV 89%	Median 28.9 months for study arm and 27.7 months for control arm
Hotta et al (53)	Study arm: oral menatetrenone 45 mg/day until recurrence; n=21 Control arm: no adjuvant therapy; n=24	Single tumour 44%; mean tumour size ≤3 cm 80%	C-P A 60%; HC V 73%	Median 19.5 months for study arm and 16.5 months for control arm
Kakizaki et al (54)	Study arm: oral menatetrenone 45 mg/day until recurrence; n=30 Control arm: no adjuvant therapy; n=30	LCSGJ stage I–III; single tumour 68%; mean tumour size 20 mm for study arm and 25 mm for control arm; vascular invasion 0%	C-P A 73%; HCV 100%	NR
Yoshida et al (55)	Study arm 1: oral menatetrenone 45 mg/day until recurrence; n=182 Study arm 2: oral menatetrenone 90 mg/day until recurrence; n=185 Control arm: the same dosage of placebo; n=181	Single tumour 71%; median tumour size 19 mm; vascular invasion 0%	C-P A 87%; cirrhosis 78%; HCV 83%	NR

C-P Child Child-Pugh class; HCV Hepatitis C virus; LCSGJ Liver Cancer Study Group of Japan; NR Not reported