(A) Studies of serum IGF-1 and IGFBP-3 levels and IGF-I/IGFBP-3 molar ratio among healthy, cirrhosis and HCC groups.

Study, year	Location, setting	Study design	Study period	Age, y	IGF-1/IGFBP-3 assay	HCC diagnosis	HCC, n	Cirrhosis case, n	Healthy controls, n	Adjusted confounders
Stuver et al, 20002	USA, Hospital-based	Case control	1995–1998	39–88	Chemiluminescence assay	Biopsy, AFP, US	73	NV	111	Gender, age
Mazziottiet et al, 200214	Italy, Hospital-based	Cohort study	1995–2000	43–81	immunoradiometric assay	US, biopsy	20	84	NV	Gender, age
Mattera et al, 200312	Italy, Hospital-based	Cohort study	NA	25–75	immunoradiometric assay	US, Biopsy	63	40	150	Age, diet
Cujic et al, 201039	Serbia, Hospital-based	Cohort study	2008	20–75	radioimmunoassay	US, CT	8	24	31	N A
Major et al, 201025	USA, population-based	Cohort study	1985–1988	50–69	ELISA	AFP, US, CT, MRI, biopsy	50	NA	400	Age,
Su et al, 201022	Taiwan, Hospital-based	Cohort study	2005–2006	20–83	radioimmunoassay	Biopsy, AFP, US	65	NA	165	Recruitment center, date of blood collection
Rehem et a,l 201140	Egypt, Hospital-based	Cohort study	2011	24–69	Immunoradiometric assay	CT or/and AFP	20	60	20	NA
Aleem et al, 201241	Egypt, Hospital-based	Cohort study	2010–2011	NA	ELISA	US, AFP	62	79	100	Age, height, BMI
Adamek et al, 201342	Poland, Hospital-based	Cohort study	2010–2012	18–63	immunoenzymetric assay, ELISA	USAFP	61	37	15	Age, gender
Lukanova et al, 20143	European countries, population-based	nested case-control study	2002–2006	35–75	ELISA	AFP, US, CT, MRI, biopsy	125	NA	247	Recruitment center, gender, age, date of blood collection
Adachi et al, 20164	Japan, population-based	nested case-control study	1997–2000	40–79	immunoradiometric assay	AFP, US, CT, MRI, biopsy	91	NA	263	gender, age, and residential area, Hepatitis viral infection, body mass index, smoking, and alcohol intake