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Page 6 of 9 Calabrò et al. Hepatoma Res 2020;6:69 I http://dx.doi.org/10.20517/2394-5079.2020.63

included the level of AST[(OR: 1.04 (1.004-1.076); P = 0.029] and presence of NASH [OR: 2.41 (1.007-5.782);
P = 0.048].

[45]
Zelber-Sagi et al. , evaluated the association between coffee consumption and hepatic steatosis onset
in a cohort of 347 patients, comparing them with a control group. Hepatic steatosis was quantified by
ultrasound and SteatoTest and the degree of fibrosis was assessed by FibroTest. During recruitment, a
questionnaire relating to coffee consumption was filled. The study found that neither the incidence nor
the prevalence of steatosis was associated with coffee consumption. Moreover, coffee consumption was
associated with a lower clinically significant percentage of fibrosis ≥ F2 (8.8% vs. 16.3%; P = 0.038) and the
multivariate logistic regression analysis related the high coffee consumption with a lower probability of
fibrosis (probability ratio = 0.49, 95% confidence interval, 0.25-0.97; P = 0.041). In a retrospective study by
[46]
Hodge et al. , a total of 1,018 patients (441 women, 577 men) affected by NAFLD, Hepatitis C (HCV), and
hepatitis B (HBV) were recruited for determining the effects of coffee and tea intake on liver stiffness (SE).
Data showed that SE was higher in males than in females (P < 0.05). HBV patients had a lower SE than
those with HCV and NAFLD. Those who drank 2 or more cups of coffee a day had a lower SE (P = 0.044).
Tea consumption had no effect on SE (P = 0.9). The study showed that coffee consumption reduces the SE
with a decrease of fibrosis and inflammation.

[47]
Alferink et al. recruited 2,424 participants (age 66.5 ± 7.4; 43% male)who were asked to fill in a
questionnaire on eating habits and lifestyle. All patients were examined by liver elastography and
ultrasonography to evaluate liver stiffness and the degree of liver steatosis. Coffee and tea consumption
were classified into: no intake (0), moderate (> 0-3) or frequent intake ≥ 3) (cups/day). Fibrosis was
defined as a measure of SE. During course of the study, univariate linear and logistic regression analyzes
were performed to examine the association between coffee, herbal /green/black tea consumption and
SE. For the regression models, multivariable adjustments were made taking into consideration age, sex,
BMI, insulin resistance, steatosis, serum ALT, alcohol intake, smoking, use of cream in coffee, use of
sugar in tea or coffee and physical activity. The results showed that the SE was inversely related to a higher
consumption of coffee (7.8%, 6.9% and 4.1% for non consumption, moderate and frequent respectively; P
= 0.006). In general, frequent coffee consumption was inversely related to SE but not to steatosis. More in-
depth analysis and studies are needed to validate the underlying mechanisms. The daily consumption of
three or more cups of coffee was linked to the presence of a low SE, regardless of many other lifestyle and
environmental factors.

CONCLUSION
Although the protective role of coffee in NAFLD is still controversial, several studies have shown that
coffee consumption in patients with NAFLD can be protective against liver steatosis, progression of fibrosis
[48]
and liver damage . The antioxidant capacity of coffee has been demonstrated in animal models of fatty
liver, in which caffeine intake improves insulin resistance and reduces the production of inflammatory
cytokines. Moreover, the weight of the animals and the intrahepatic levels of glucose were reduced with
coffee consumption. However, not all the studies were concordant on the protective effect of coffee against
NAFLD: controversial results may be due to the heterogeneity of the patients analyzed, the different
protocols of research, and the different methods of collecting data. Furthermore, it should be emphasized
that the content of caffeine and the different compounds typical of coffee can be influenced by the type of
coffee examined, the type of roasting, the volume of water used, and the type of grinding: all these elements
should therefore be standardized to avoid variations in the concentration of the most active compounds.

In conclusion, the overall trend emerging from the literature review suggests that regular coffee
consumption might be a protective factor against the evolution of NAFLD complications, especially liver
fibrosis. Additional studies should be carried out to further characterize the correlation between coffee and