Table 2

The associations reported by the studies meeting the inclusion criteria for the main coffee–HCC meta-analysis

Study	Coffee (cups per day, unless specified)	Participants	Cases (cumulative rate/1000)	Adjusted RR (95% CI)	Adjustments
Cohort studies
Inoue et al 36	Almost never 1–2/week 3–4/week 1–2 3–4 ≥5	29 423 17 159 10 316 23 753 7316 2485	161 (5.5) 65 (3.8) 36 (3.5) 54 (2.3) 15 (2.1) 3 (1.2)	1 (ref) * 0.75 (0.56 to 1.01) * 0.79 (0.55 to 1.14) * 0.52 (0.38 to 0.73) * 0.48 (0.28 to 0.83) * 0.24 (0.08 to 0.77) *	Age, gender, alcohol, smoking, green tea, study area, green vegetable intake
Kurozawa et al 35	Non-drinkers <1 ≥1	24 556 15 259 44 151	103 (4.2) 57 (3.7) 98 (2.2)	1 (ref) * 0.83 (0.54 to 1.25) * 0.5 (0.31 to 0.79) *	Age, gender, alcohol, smoking, T2DM, liver disease, education
Shimazu et al (cohort 1)39	Never Occasionally ≥1	4938 9507 7959	29 (5.9) 25 (2.6) 16 (2.0)	1 (ref)^† 0.56 (0.33 to 0.97)^† 0.53 (0.28 to 1.00)^†	Age, gender, alcohol, smoking, liver disease
Shimazu et al (cohort 2)39	Never Occasionally ≥1	6954 14 130 17 619	12 (1.7) 21 (1.5) 14 (0.8)	1 (ref)^† 1.05 (0.52 to 2.16)^† 0.68 (0.31 to 1.51)^†	Age, gender, alcohol, smoking, liver disease
Hu et al 38	0–1 2–3 4–5 6–7 ≥8	6150 12 681 17 991 13 726 9775	20 (3.3) 30 (2.4) 33 (1.8) 28 (2.0) 17 (1.7)	1 (ref) * 0.66 (0.37 to 1.16) * 0.44 (0.25 to 0.77) * 0.38 (0.21 to 0.69) * 0.32 (0.16 to 0.62) *	Age, gender, alcohol, smoking, T2DM, liver disease, education, BMI, study year
Johnson et al 41	Non-drinkers 0–<1 1–<2 2–<3 ≥3	119 973 (PY) 70 762 (PY) 236 215 (PY) 190 567 (PY) 37 505 (PY)	69 38 149 92 14	1 (ref) * 0.94 (0.63 to 1.40) * 1.17 (0.87 to 1.56) * 0.78 (0.56 to 1.07) * 0.56 (0.31 to 1.00) *	Age, gender, alcohol, smoking, T2DM, education, BMI, dialect group, year of recruitment, black and green tea
Lai et al 23	Never drinkers >0 to <1 1 to <2 2 to <3 3 to <4 ≥4 per extra cup	667 3094 7204 8086 4515 3471	9 (13.5) 36 (11.6) 60 (8.3) 47 (5.8) 22 (4.9) 20 (5.8)	1.35 (0.65 to 2.82)^† 1 (ref)^† 0.73 (0.48 to 1.12)^† 0.52 (0.33 to 0.82)^† 0.45 (0.26 to 0.78)^† 0.53 (0.30 to 0.95)^† 0.82 (0.73 to 0.93)^†	Age, alcohol, smoking, T2DM, education, BMI, tea, cholesterol, marital status, ATBC intervention arm§
Bamia et al 21	Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5	98 148 100 953 95 231 96 413 96 054	47 (0.5) 49 (0.5) 38 (0.4) 36 (0.4) 31 (0.3)	1 (ref) * 0.85 (0.56 to 1.29) * 0.63 (0.39 to 1.02) * 0.49 (0.29 to 0.82) * 0.28 (0.16 to 0.5) *	Stratified for age and centre; adjusted for gender, alcohol, smoking, T2DM, education, BMI, physical activity, energy intake, tea
Setiawan et al 15	Never <1 1 2–3 ≥4	44 438 31 056 45 717 32 593 8218	119 (2.7) 111 (3.6) 137 (3.0) 67 (2.1) 17 (2.1)	1 (ref)* 1.14 (0.88 to 1.48)* 0.87 (0.67 to 1.11)* 0.62 (0.46 to 0.84)* 0.59 (0.35 to 0.99)*	Age, gender, alcohol, smoking, T2DM, education, BMI, race
Petrick et al 22	Non-drinker >0 to <1 1 to <2 2 to 3 >3 per extra cup	172 950 164 977 179 781 370 786 161 116	85 (0.5) 138 (0.8) 149 (0.8) 255 (0.7) 97 (0.6)	1 (ref)* 1.24 (0.94 to 1.64)* 1.16 (0.88 to 1.52)* 0.89 (0.68 to 1.15)* 0.73 (0.53 to 0.99)* 0.90 (0.85 to 0.94)*	Age, gender, alcohol, smoking, BMI, race, cohort
Case–control studies		Cases	Controls
Gallus et al (Italian and Greek studies combined)37	Non-drinkers 1 2 ≥3	129 231 292 178	256 432 582 637	1 (ref)^‡ 1.2 (0.9 to 1.6)^‡ 1.0 (0.7 to 1.3)^‡ 0.7 (0.5 to 1.0)^‡	Age, gender, alcohol, smoking, education, BMI, T2DM, hepatitis, study
Gelatti et al 42	No consumption 1–2 3–4 ≥5	44 119 69 18	59 206 163 72	1 (ref)^‡ 0.8 (0.4 to 1.3)^‡ 0.4 (0.2 to 0.8)^‡ 0.3 (0.1 to 0.7)^‡	Age, gender, alcohol, HBV, HCV
Ohfuji et al 43	Non-drinkers <1 ≥1	25 19 29	63 74 116	1 (ref)^‡ 0.61 (0.18 to 2.03)^‡ 0.38 (0.13 to 1.12)^‡	Alcohol, smoking, BMI, duration of liver disease, disease severity, family history, interferon therapy, other caffeinecontaining beverage
Tanaka et al 33	None Occasional 1–2 ≥3	127 53 17 12	268 496 268 221	1 (ref)^‡ 0.33 (0.22 to 0.48)^‡ 0.27 (0.15 to 0.48)^‡ 0.22 (0.11 to 0.43)^‡	Age, gender, alcohol, smoking, HBV, HCV
Montella et al 32	Abstainers <14/week 14–20 21–27 ≥28	27 67 50 27 14	41 116 104 88 63	2.28 (0.99 to 5.24)^‡ 1 (ref)^‡ 0.54 (0.27 to 1.07)^‡ 0.57 (0.25 to 1.32)^‡ 0.43 (0.16 to 1.13)^‡	Age, gender, alcohol, smoking, education, centre, HBV, HCV
Leung et al 45	No coffee habit 1–3/week ≥4 week	86 11 12	82 17 26	1 (ref)^‡ 0.58 (0.24 to 1.36)^‡ 0.41 (0.19 to 0.89)^‡	Age, gender, alcohol, smoking, tea, physical activity
Stucker et al 44	0–1 2 >2	92 45 28	57 37 48	1 (ref)^‡ 0.67 (0.3 to 1.3)^‡ 0.36 (0.2 to 0.7)^‡	Alcohol

*Reported as HR.
†Reported as RR.
‡Reported as OR.
§Participants were from another trial investigating vitamin E supplementation in the form of ATBC.
ATBC, α-tocopherol or β-carotene; BMI, body mass index; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; PY, person years; RR, relative risk; T2DM, type 2 diabetes mellitus.