Table 1.

Summary of studies investigating the impact of coffee consumption on NAFLD incidence, prevalence, and liver fibrosis.

Study	Study Design	Population	NAFLD Diagnosis	Steatosis Severity	Fibrosis Severity	Coffee Intake Measurement	Main Finding	RR/HR/OR Estimates for Extreme Categories of Coffee Intake (95% CI)	Adjustments for Confounding Variables	NOS
Chung et al., 2020 [21]	Retrospective longitudinal cohort	91,436 subjects participating in a comprehensive health-screening program were followed for a mean of 2.8 years, 13,362 (15% developed fatty liver)	Ultrasound	Steatosis incidence: increase in liver echogenicity compared with the renal cortex echogenicity		Self-administered food frequency questionnaire	No association between fatty liver incidence and the amount of coffee consumption at baseline	HR 1.09 (0.97–1.22)	Age, sex, education, exercise, smoking, alcohol intake, centre and year, BMI, total energy intake, triglyceride, LDL-C, HDL-C, glucose, alanine aminotransferase, aspartate aminotransferase, change of alcohol, change of BMI, and change of exercise	8
Zhang et al., 2020 [28]	Cross-sectional	555 NAFLD patients from multi-centre hepatology clinics	Radiological features, liver histology, or elevated alanine aminotransferase or aspartate aminotransferase levels with a CAP value ≥ 248 dB/m	Elastography: severe hepatic steatosis: CAP threshold of 280 dB/m	Elastography: advanced fibrosis: LSM threshold of 10 kPa	Standardized, self-administered questionnaires	Inverse association between coffee consumption and advanced fibrosis No association between coffee consumption and severe hepatic steatosis	OR 0.49 (0.27–0.88), p = 0.02 OR 0.92 (0.59–1.44), p = 0.71	Age, sex, smoking and alcohol status, coffee, tea, and soft drinks drinker, time spent on different physical activities, energy expenditure, physical activity level and meeting physical activity guidelines (%), obesity and type 2 diabetes, and participating centre	8
Veronese et al., 2018 [24]	Cross-sectional	2819 randomly sampled participants from electoral rolls Absence of fatty liver in 1627 subjects and 916 with NAFLD (134 patients with Liver Steatosis Score of 6)	Ultrasound	Fatty liver score ranged from 0 to 6, with higher values indicating a greater severity		Self-reported validated semi-quantitative food frequency questionnaire	No association between coffee consumption and lower odds of liver steatosis	OR 0.97 (0.71–1.32), p = 0.84	Age, sex, smoking status, presence of diabetes, gastric ulcer, cancer, acute myocardial infarction, waist circumference, systolic and diastolic blood pressure, daily energy, and alcohol intake	8
Alferink et al., 2017 [25]	Cross-sectional	Population-based cohort of 2424 participants (35% steatosis)	Ultrasound	Presence or absence of a hyper-echogenic liver parenchyma	Transient elastography: liver stiffness measurements (LSM) ≥8.0 kPa	Validated 389-item food frequency questionnaire	Independent association between frequent coffee consumption and lower probability of significant liver fibrosis No significant association between coffee intake and steatosis	OR 0.39 (0.18–0.86), p = 0.005 OR 1.15 (0.75–1.77), p = 0.192	Tea, energy intake, BMI, gender, age, steatosis, alanine aminotransferase, excessive alcohol intake, current or former smoking and HOMA-IR, soda consumption, cream and sugar use, dietary quality, and physical activity Tea, energy intake, BMI, gender, age, HOMA-IR, excessive alcohol intake, current or former smoking	9
Katsagoni et al., 2017 [27]	Case-control	100 newly ultrasound-proven NAFLD patients (21 with NASH), 55 healthy controls matched for age, sex, and BMI	Elevated alanine aminotransferase and/or gamma- glutamyl transpeptidase levels, elastography, and evidence of hepatic steatosis on ultrasound (available for 85) and/or compatible liver histology (n = 32)	Evidence of hepatic steatosis at ultrasonography Biopsy: NASH Diagnosis: NAFLD Activity score (NAS) ≥ 5		Semi-quantitative validated food frequency questionnaire	Inverse association between coffee intake and NAFLD presence (OR 0.68, 95% CI 0.49–0.94, p = 0.02) Lost its significance once adjusted for adiponectin and TNF-a	OR 0.72 (0.49–1.04), p = 0.07	Age, sex, waist circumference, HOMA-IR, adiponectin, and TNF-a	7
Zelber-Sagi et al., 2015 [23]	Cross-sectional and prospective cohort	Cross-sectional cohort 347 general population, 31% diagnosed with NAFLD Prospective cohort A subgroup of patients without fatty liver at baseline who were followed up for 7 years (n = 147)	Ultrasound and SteatoTest	Hepatorenal index (HRI) on US, NashTest (borderline NASH or definite NASH) SteatoTest (≥5%, ≥S1–S2)	FibroTest (significant fibrosis (≥F2))	Interviewer-administrated questionnaire and detailed semiquantitative food-frequency questionnaire	Cross-sectional cohort: Inverse association between coffee consumption and significant liver fibrosis and no association with the development of steatosis Prospective cohort: No association between coffee consumption and NAFLD incidence	NAFLD prevalence 0.92 (0.57–1.50), p = 0.75 Hepatic Fibrosis:0.49 (0.25–0.97), p = 0.04 NAFLD Incidence: 0.72 (0.28–1.85), p = 0.501	Current smoking, sugar intake, physical activity (minutes per week), serum cholesterol levels, and dietary fat and calories intake Current smoking, sugar intake, physical activity	8
Imatoh et al., 2015 [16]	Cross-sectional	1024 Japanese male workers receiving annual health checkups Non-steatosis (n = 270) Steatosis (n = 754)	Ultrasound	No, mild, or moderate-to-severe hepatic steatosis		Self-reported questionnaire	Dose-dependent protective effect of coffee on the prevalence of hepatic steatosis	OR 0.59 (0.38–0.90), p = 0.03	BMI, age, smoking status, alcohol drinking, and green tea consumption	7
Graeter et al., 2015 [26]	Cross-sectional	Random population-based sample with 1452 subjects (381 diagnosed with hepatic steatosis)	Ultrasound	No steatosis and steatosis grade I, II and III		Standardized questionnaire	No association between hepatic steatosis and coffee consumption	OR 0.77 (0.44–1.34), p = 0.81	Age, BMI, gender, metabolic syndrome, and physical activity	8
Bambha et al., 2014 [11]	Cross-sectional	782 biopsy-proven NAFLD patients; Advanced fibrosis (>stage 2) in 25% (n = 199) NASH (definite or probable): in 79% (n = 616)	Biopsy	Presence versus absence of NASH histology ((1) definite steatohepatitis; (2) definitely not steatohepatitis; and (3) borderline steatohepatitis)	None to moderate (≤Stage 2) or advanced (>Stage 2)	Self-reported validated dietary questionnaire	Significant association between coffee intake and decreased odds of advanced fibrosis in patients with lower HOMA-IR	OR 0.68 (0.52–0.89), p = 0.005	Age, sex, race, waist circumference, aspartate transaminase, gamma-glutamyl transferase diabetes, smoking, alcohol, biopsy length, HOMA-IR, and interaction between coffee and HOMA-IR	8
Anty et al., 2012 [29]	Cross-sectional	195 severely and morbidly obese patients, referred for bariatric surgery of which NASH was present in 19.5%	Biopsy	NAFLD activity score (NAS) simple steatosis (NAS ≤ 2), borderline (3≤ NAS ≤ 4), or definitive NASH (NAS ≥ 5)	Significant fibrosis (F ≥ 2)	Interviewer- administered questionnaire	Regular coffee consumption was an independent protective factor for significant fibrosis	OR: 0.752 (0.578–0.980), p = 0.04	Aspartate aminotransferase, presence of NASH, presence of the metabolic syndrome, and level of HOMA-IR	7
Funatsu et al., 2011 [22]	Nested case-control	1236 subjects followed for 5 years; of those, 164 males with fatty liver were matched (age, BMI, and exercise level) with 328 without fatty liver	Ultrasound	Steatosis incidence: a bright liver, an increase in the liver−kidney contrast, and/or a decrease in liver deep echo		Self-administered questionnaire	Daily coffee intake was inversely associated with fatty liver development	0.74 (0.61–0.89), p = 0.001	Age, BMI, exercise, daily alcohol intake, and changes in BMI, exercise level, and daily alcohol intake over time	7

Abbreviation: BMI, body mass index; HR, hazard ratio; NAFLD, non-alcoholic fatty liver disease; NASH, alcoholic steatohepatitis; NOS, the Newcastle−Ottawa Scale; OR, odds ratio; RR, relative risk.