. 2020 Mar 9;14(6):792–807. doi: 10.5009/gnl19163

Table 1.

Characteristics of the Studies Included in the Meta-Analysis

First author (year)	Country	Study design	Mean follow-up, yr	Sex	Age, yr*	Participants (total)	Case (HCC incidence)	Case (HCC induced death)	Case (liver disease-related death)	Case (all-cause death)	Classification of alcohol consumption	Adjusted covariates
Allen (2009)²³	UK	Cohort	7.2	F	55	12,980,296	337				≤2 vs none, 3–6, 7–14, ≥15 drinks/wk	Age, region of residence, socioeconomic status, BMI, smoking, physical activity, use of oral contraceptives, and hormone replacement therapy
Persson (2013)²²	USA	Cohort	10.5	M/F	50–71	404,743	435		785		<1 vs none, 1–3, >3 drinks/day	Sex, age, race, education, smoking, BMI, and diabetes
Kawamura (2016)²⁵	Japan	Cohort	5.4	M/F	19–96	9,959	49				<20 vs 20–39, 40–69, ≥70 g/day	Sex, age, BMI, alcohol intake, albumin, bilirubin, AST, ALT, LDH, G-GTP, PLT, DM, uric acid, total cholesterol, TG, LDL, HDL
Schwartz (2013)²⁴	Finland	Cohort	7	M	50–69	29,133	194		213		<5.33 vs 5.33–20.44, >20.44 g/day	Age, education, smoking, BMI, DM, study arm
Setiawan (2016)²⁶	USA	Cohort	19.6	M/F	45–75	38,684	189				None vs <2, ≥2 drinks/day	Cohort entry, education, BMI, alcohol intake, smoking status, diabetes, vigorous activity, and sex
		Cohort (USA born)	19.6	M/F	45–75	18,485			194
		Cohort (foreign born)	19.6	M/F	45–75	18,379			104
Michikawa (2012)²⁷	Japan	Cohort	7	M/F	40–69	17,654	104				<150 vs 150–450 ≥450 g/wk	Age, sex, area, alcohol consumption, BMI, diabetes, coffee consumption, HBsAg, and anti-hepatitis C virus antibody
Chen (1996)²⁸	Taiwan	Nested case-control	2	M/F	30–65	156	33				None vs <20, ≥20 L/yr	Age, sex
Ohishi (2008)²⁹	Japan	Nested case-control	32	M/F	67.6	868	224				None vs 0–20, 20–40, ≥40 g/day	Hepatitis virus infection, continuous alcohol consumption, smoking habit, coffee drinking, BMI, DM, and radiation dose to the liver
Koh (2011)³⁰	Singapore	Nested case-control	11.5	M/F	45–74	366	92				None vs less than daily <2, ≥2 drinks/day	Gender, age at recruitment (yr), year of recruitment, dialect group (Hokkien, Cantonese), and the level of education, BMI (<20, 20–24, >24 kg/m²), DM (yes, no), and cups of coffee per day
Trichopoulos (2011)³¹	Europe	Nested case-control	8.9	M/F	25–70	344	115				M <10, F <5 vs M 10–40, F 5–20, M ≥40, F ≥20 g/day	All indicated possible risk factors
Yuan (2004)³²	USA	Nested case-control	15	M	18–74	465	245				None vs 0–2, 2–4, >4 drinks/day	Age, gender, race, and level of education, smoking status, number of alcoholic drinks per day, and history of diabetes
Loftfield (2016)³³	Finland	Nested case-control	22	M	50–69	391	138				≤11.3 vs >11.3 g/day	Age-adjusted
Yi (2018)³⁴	Korea	Cohort	10.5	M/F	53.0	504,646	2,744				None vs <10, 10–39, ≥40 g/day	Age, sex, smoking status, alcohol use, physical activity, income status, BMI, diabetes status, cirrhosis and hepatitis B virus and C virus infection
Kim (2010)³⁵	Korea	Cohort	5	M	48.3	919,199		1,506		16,108	None vs 1–14.9, 15–29.9, 30–89.9, ≥90 g/day	Age, residential (urban, rural), smoking status (current, former, never), ≥3 times/wk regular exercise (yes, no), BMI (kg/m², continuous), systolic and diastolic blood pressure (mm Hg, continuous), and fasting blood sugar (mg/dL, continuous)
Kim (2010)³⁵	Korea	Cohort	5	F	49	422,194		174		3,267	None vs 1–14.9, ≥15 g/day	Age, residential (urban, rural), smoking status (current, former, never), ≥3 times/wk regular exercise (yes, no), BMI (kg/m², continuous), systolic and diastolic blood pressure (mm Hg, continuous), and fasting blood sugar (mg/dL, continuous)
Yi (2010)³⁶	Korea	Cohort	20.8	M	66.3	2,696		36			None vs <138, <540, ≥540 g/wk	Age (year of recruitment), history of chronic disease, smoking habit, ginseng intake, pesticide use, BMI, and education status
Yi (2010)³⁶	Korea	Cohort	20.8	F	66.9	3,595		52			None vs <12, ≥12 g/wk	Age (year of recruitment), history of chronic disease, smoking habit, ginseng intake, pesticide use, BMI, and education status
Yang (2012)³⁷	China	Cohort	15	M	40–79	220,000		1,115		20,977	None vs <140, 140–279, 280–419, 420–699, ≥700 g/wk	Age, area, smoking and education
Jee (2004)³⁸	Korea	Cohort	10	M/F	30–95	1,329,525		3,341			None vs 1–24.9, 25–49.9, 50–99.9, ≥100 g/day	Age, age squared, smoking, alcohol use, and diabetes
Joshi (2008)³⁹	Korea	Cohort	6	M	30–59	548,530		998			None vs 1–24, 25–49, 50–99, ≥100 g/day	Age, fasting serum glucose, BMI, alcohol intake and tobacco smoking, HBsAg
Jung (2012)⁴⁰	Korea	Cohort	9.3	M/F	>20	15,683		85			≤90 vs none, 90.01–252, 252.01–504, >504 g/wk	Age, sex, BMI, smoking habit, geographic area, and educational attainment
Kono (1986)⁴¹	Japan	Cohort	19	M		5,135		51		1,283	None/past vs occasional, <2, ≥2 go of sake/day	Age, smoking
Park (2006)⁴²	Korea	Cohort	7	M	50.8	14,578		2,013			None vs 1–124.1 ≥124.2 g/wk	Age, alcohol consumption, BMI, fasting serum glucose level, cholesterol level, physical activity, food preference, blood pressure, and other comorbidities (heart disease, liver disease, and cerebrovascular disease)
Shih (2012)⁴³	Taiwan	Cohort	10	M/F	20–75	2,273		1,488			None vs ex-drinker, <19.4, 19.5–46.1, 46.2–106.9, ≥107 g/day	Adjusted for age at recruitment, sex, maximum tumor size (<3, 3 to <5 or 5 cm), number of lesions (1, 2–3 or 4), serum a-fetoprotein levels (<20, 20–151, 152–1,519 or 1,520 ng/mL), cigarette smoking (yes or no), history of liver cirrhosis and status of HBsAg and anti-HCV
Yi (2016)⁴⁴	Korea	Cohort	6	M	58.8	187,897			338		<1 vs 1–6, 7–13, 14-27, ≥28 drinks/wk	Adjusted for age at entry, smoking status, physical activity, household income, and BMI
Younoszai (2014)⁴⁵	USA	Cohort	14.6	M/F	20–74	8,966			26	1,130	<20 (M) (10 [F]) vs >20 g/day	Statin use, age, male, race, alcohol consumption, obesity, diabetes, HTN, cancer, elevated liver enzyme
Fuchs (1995)⁴⁶	USA	Cohort	12	F	30–55	85,709				836	0 vs 0.1–1.4, 1.5–4.9, 5.0–14.9, 15.0–29.9, ≥30 g/day	Adjusted for age (in 5-yr categories), smoking status, BMI (in quintiles), regular aspirin use (2 days/wk), regular vigorous exercise (1 day/wk), high plasma cholesterol level, diabetes, HTN, myocardial infarction in a parent at 60 yr of age, past or present oral-contraceptive use, menopausal status, past or present postmenopausal hormone use, and energy-adjusted intake of dietary fiber and saturated fat
Marugame (2007)⁴⁷	Japan	Cohort	11.9	M/F	40–69	41,702 (M)/ 47,044 (F)				2,658 (M)/ 9,338 (F)	Occasional drink vs 1–149, 150–299, 300–449, 450 g/wk	Adjusted for age at baseline (continuous), study area (nine public health center areas), smoking status, BMI, green vegetable intake (3–4 times/wk and almost every day), and leisure-time physical activity
Ferrari (2014)⁴⁸	Europe	Cohort	12.6	M	25–70	101,935 (M)/247,795 (F)				8,964 (M)/11,492 (F)	0.1–4.9 vs never, 5–14.9, 15–29.9, 30–59.9, ≥60 g/day	Age at recruitment, BMI and height, former drinking, time since alcohol quitting, smoking status, duration of smoking, age at start smoking, educational attainment and energy intake
Saito (2018)⁴⁹	Japan	Cohort	18.2	M/F	40–69	102,849				15,203	Never vs 1–149, 150–299, 300–449, 450–599, ≥600 g/wk	Adjusted for age, smoking status (never, former, <20, ≥20 cigarettes/day), BMI (<18.5, 18.5 to <25, 25 to <30, ≥30), history of HTN, flushing response, history of diabetes, leisure-time sports or physical exercise, intake of coffee and green tea (almost never, ≥1 cup/wk, and ≥1 cup/day), energy intake, intakes of fruits, vegetables, fish, meat, dairy products, and job status

HCC, hepatocellular carcinoma; M, male; F, female; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactic dehydrogenase; G-GTP, gamma glutamyl transpeptidase; PLT, platelet count; DM, diabetes mellitus; TG, triglyceride; LDL, low density lipoprotein; HDL, high density lipoprotein; HBsAg, hepatitis B surface antigen; HTN, hypertension.

*Mean or range.