Editorial
Coffee and tea breaks for liver health Salvatore Petta1,⇑, Giulio Marchesini2 1
Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy; 2Department of Medical and Surgical Sciences (DIMEC), ‘‘Alma Mater” University, Bologna, Italy See Article, pages 339–348
Let food be your medicine (Hippocrates, 400 B. C.) The quality of diet, calorie intake and physical activity/sedentariness are pivotal drivers in the interplay between health and noncommunicable diseases, and the battle against the risks associated with Western-type behaviour is the top priority of medical societies and health institutions. Unfortunately, any attempt at adopting a healthy lifestyle is counteracted by unhealthy environmental pressure, which favours the diseases of affluence, including liver diseases. The typical Mediterranean diet, characterized by the consumption of complex carbohydrates, fibreand antioxidant-rich vegetables, and polyunsaturated fatty acids, is considered the prototype of a healthy diet associated with favourable hepatic outcomes. Unfortunately, this diet is no longer the standard food choice even in the Mediterranean area, where it has largely been replaced by a Western-type diet, rich in saturated fatty acids and sugars, which are associated with a higher risk of metabolic liver disease. In parallel with unhealthy behaviours, there is a larger and larger use of nutraceuticals everywhere. Nutraceuticals are products derived from food sources, supposed to provide medical or health benefits in addition to their nutritional value; they include herbal and plant extracts, vitamins, minerals, amino acids. Their beneficial effects focus on prevention more than cure, with an expanding market with a lot of implications for producers, regulatory agencies, distributors and consumers. Coffee and tea are the most frequently used beverages prepared from plants worldwide; they are consumed primarily for their taste and flavour, but are also considered to be healthy for several organs and tissues, including the liver. Coffee is prepared from the seeds of a plant originally grown in the Arab area in the 15th century and is the second most traded commodity in the world, with lots of varieties and preparations. The consumption of coffee is increasing everywhere, headed by Finnish people with a per capita use of nearly 10 kg seeds/year and over 2.5 cups/day. Tea comes from Southwest China and hundreds of varieties are available as well; it was initially prepared as green tea, with
Received 14 April 2017; accepted 25 April 2017 q DOI of original article: http://dx.doi.org/10.1016/j.jhep.2017.03.013. ⇑ Corresponding author. Address: Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy, Piazza delle Cliniche, 2, 90127 Palermo, Italy. Tel.: +39 091 655 2170; fax +39 091 655 2156. E-mail addresses: [email protected], [email protected] (S. Petta).
the leaves of Camellia Sinensis dipped in hot water, before any oxidation process takes place by fermentation. Contrary to expectations and the long-dated British tradition, Turkey is the country with the largest tea use with 7.5 kg/year per person. Other herbal teas are consumed throughout the world in different amounts, in selected settings and according to specific cultures. Overall, there is some evidence that the consumption of these beverages may confer health benefits. However, it is difficult to support biological plausibility, to provide guidance as to the dose, and some possible warnings about safety should be taken into account.
What is known about coffee, tea and the liver? Several cohort studies assessed the association between coffee intake and the presence/development of non-alcoholic fatty liver disease (NAFLD), or severity of liver damage in patients with chronic liver diseases. The largest study comes from the US and was performed on a cohort of 18,550 individuals.1 After adjusting for clinico-metabolic confounders and other dietary components, the study found a protective effect of caffeine intake on the presence of NAFLD, identified by an unexpected rise of liver enzymes.1 The results have been confirmed in a recent large multi-ethnic study,2 while other studies did not support any association between coffee and both the presence and occurrence of NAFLD.3–5 Conflicting data were also reported on the association between coffee intake and the severity of liver damage in NAFLD patients. Two cross-sectional studies showed that a large amount of coffee was protective towards histologically diagnosed liver fibrosis,6,7 whereas the largest study in this field, in 782 biopsy-proven NAFLD patients, limited the protective effect to patients without insulin resistance, not to the entire cohort.8 In patients with chronic liver disease due to hepatitis C9–11 or hepatitis B2,12,13 viruses or alcohol abuse,14 most studies support a protective effect of coffee drinking on liver damage.9,10,12,14 Finally, solid data are in favour of a beneficial role of coffee use on the risk of hepatocellular carcinoma (HCC), as summarized in a recently updated meta-analysis,15 and of a reduced liverrelated mortality in cohort studies.16,17 In summary, there is some evidence for a beneficial effect of coffee on the liver, with differences possibly due to the baseline characteristics of the populations and to the methods used for estimating coffee drinking and the severity of liver damage.
Journal of Hepatology 2017 vol. 67 j 221–223
Editorial 160
Caffeine amount (mg)
140
140
135
120
120 105
100
100
85 65 60
80
80
80
70
60
57
60
50
45 40 35
40
32
35
20
35
20
20
48 39
41
30
26
20 10
10
e (3 rgy 30 dr m ink l) s
En
ga (3 r-fr 30 ee m co l) la
Su
C o (3 la d 30 rin m ks l)
Ye r (3 ba 30 m m ate l)
G r (1 een 50 t m ea l)
Ic (3 ed 30 te m a l)
T (1 ea 50 ba m g l)
pr e (3 sso 0 m c of l) fe e
Es
lu (1 ble 25 co m ffe l) e
So
Fi
lte (1 red 25 co m ffe l) e
0
Fig. 1. Sources of caffeine and amount per serving in coffee, tea and other beverages. Data are expressed as minimum, maximum and average (in red), according to different preparations and brands. Redrawn and modified from data of the Institute for Scientific Information on Coffee (www.coffeeandhealth.org). Note that the amount of caffeine in decaffeinated coffee and hot chocolate is negligible (\10 mg/serving).
On the contrary, only limited and not univocal evidence is available on the interplay between liver and tea consumption. As part of the NHANES I Epidemiologic Follow-up Study, a 20-year follow-up study including nearly 10,000 participants, drinking coffee and tea together decreased the cumulative incidence of chronic liver disease, particularly in subjects at higher risk of liver disease, but no separate analysis on tea consumption was provided.18 In patients with HCV infection, tea consumption did not show any significant effect on liver outcomes,10 while caffeinated tea drinking in non-coffee consumers was associated with a reduced risk of advanced fibrosis.9 Two Western studies reported contrasting results about the impact of tea drinking and HCC occurrence,17,19 while a recent meta-analysis largely involving Asian populations reported a protective effect of green tea against HCC occurrence.20 Finally, cohort studies did not show any positive effect of both black and green tea on liver-related death.17,18 What is new? In the present issue of the Journal, Alfering et al.21 report on the association of both coffee and tea drinking with the presence of steatosis and fibrosis in a cohort of 2,424 individuals from the Rotterdam study – an ongoing population-based cohort study. Ultrasonography-assessed steatosis was present in about 30% of the individuals; clinically relevant hepatic fibrosis, estimated by FibroScan, was present in 5%. Notably, drinking 3 or more cups of coffee per day, compared with no coffee, was protective against clinically relevant fibrosis, and both coffee and herbal tea consumption were independently associated with log-transformed liver stiffness. Finally, no association was found between either coffee or tea drinking and the presence of steatosis. These results are in keeping with those reported in a much smaller study, where fibrosis was tested by a patented test (FibroTest).4 The study by Alfering et al. qualifies as the largest study ever reported on the relationship between coffee, tea and liver health in a general population, the only one also reporting on tea intake,
222
and measuring the severity of fibrosis by a reliable, widely available method, i.e. liver stiffness by FibroScan. In addition, all results were confirmed after adjusting for different demographic, clinical and metabolic risk factors as well as for calorie intake and other nutrients. The beneficial effect of coffee on liver fibrosis increased after adjusting for confounders, suggesting that big coffee consumers also have unhealthy lifestyles, it was more pronounced in the subgroup of patients with fatty liver, and was also confirmed in patients with normal ALT and in subgroups where the food frequency questionnaire was either administrated at the time of liver evaluation or 5.8 years before. Finally, in the analysis of tea intake, the study not only considered overall tea intake, but also took into account the potentially different effect of black, green and herbal tea on liver outcomes. These are the main strengths of the study, but the results should be interpreted with caution as: 1) the study is limited to an elderly Caucasian population (mean age, 66 years); 2) the prevalence of coffee consumers is very high (93%), so big coffee consumers – the cohort protected from severe liver fibrosis – are compared to a very small group of individuals; 3) the prevalence of tea consumers is also high (85%), but the amount of tea intake is low, thus underestimating a potential protective effect of tea and especially of green tea, as reported in Asian populations; and 4) the lack of any effect of both tea and coffee on hepatic steatosis, already reported in the literature, might depend on the scarce sensitivity of ultrasonography. As a common concluding remark, the authors suggest that further studies using more objective non-invasive tools, like controlled attenuation parameter, are needed to define this issue. In our opinion a more pressing question remains before the results may be turned into recommendations, as detailed below. How can we explain the biological effects of coffee and tea on the liver? More than 100 components are present in coffee and tea, including polyphenols and caffeine, which are contained in both beverages in very different and variable amounts. Notably, caffeine content
Journal of Hepatology 2017 vol. 67 j 221–223
JOURNAL OF HEPATOLOGY may be very high in a few green tea brands, totally absent in a few herbal teas (as an example, Chamomile tea) and both caffeine and polyphenols are also present in several edulcorated drinks associated with the obesity epidemics and NAFLD (Fig. 1). Experimental data, reviewed by Salamone et al.22 showed that caffeine inhibits hepatic stellate cell proliferation, thus exerting an anti-fibrogenic effect via adenosine receptor blockade. In addition, caffeine was reported to have haemodynamic effects in a rat model of portal hypertension, decreasing portal pressure, porto-systemic shunting and hepatic angiogenesis. Polyphenols, namely chlorogenic acid, have a potent antioxidant, anti-inflammatory and hepatoprotective effect independent of caffeine,22 and synergistically act with caffeine on fibrosis development. However, the amount and quality of polyphenols and related antioxidant components is dependent on coffee, tea and herbal tea varieties and by the method of preparation, and might be the basis to explain the variable positive effects on hepatic fibrosis.22 While the protective effects of both coffee and tea on liver fibrosis are supported by both epidemiological and experimental evidence, conflicting results are available on the association with fatty liver. A recent meta-analysis reported a protective effect of both coffee and tea on the risk of the metabolic syndrome;23 experimental studies suggested a modest antisteatogenic effect of both beverages,22 but clinical studies were negative.2–5 Thus, in the complex human model, coffee and tea might in part prevent fatty liver, but are more likely to act as moderators of the detrimental effect of second hits, leading to inflammation and fibrosis.
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Conclusions There is an increased interest in diet and nutrition in liver diseases. A balanced diet, mostly resembling the Mediterranean diet, remains the cornerstone to reduce obesity and the risk of metabolic liver disease, and in patients with chronic liver diseases, to reduce the risk of complications, irrespective of aetiology. Should we add regular coffee and tea breaks to our daily life? Before this policy can be recommended, prospective studies are needed to identify the optimum amounts and the type(s) of coffee and tea leading to more favourable liver outcomes. Nutraceuticals are largely used with several indications without any convincing evidence; the risk of rare but severe liver toxicity associated with green tea use, as well as the cardiovascular effects of caffeine, should not be forgotten before supporting a diffuse implementation of these beverages.
[15]
[16]
[17]
[18]
[19]
[20]
References [21] [1] Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012;35:76–82. [2] Setiawan VW, Porcel J, Wei P, Stram DO, Noureddin N, Lu SC, et al. Coffee drinking and alcoholic and nonalcoholic fatty liver diseases and viral hepatitis in the multiethnic cohort. Clin Gastroenterol Hepatol 2017. http://dx.doi.org/10.1016/j.cgh.2017.02.038. [3] Gutierrez-Grobe Y, Chavez-Tapia N, Sanchez-Valle V, Gavilanes-Espinar JG, Ponciano-Rodriguez G, Uribe M, et al. High coffee intake is associated with
[22] [23]
lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity. Ann Hepatol 2012;11:350–355. Zelber-Sagi S, Salomone F, Webb M, Lotan R, Yeshua H, Halpern Z, et al. Coffee consumption and nonalcoholic fatty liver onset: a prospective study in the general population. Transl Res 2015;165:428–436. Catalano D, Martines GF, Tonzuso A, Pirri C, Trovato FM, Trovato GM. Protective role of coffee in non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci 2010;55:3200–3206. Anty R, Marjoux S, Iannelli A, Patouraux S, Schneck AS, Bonnafous S, et al. Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery. J Hepatol 2012;57:1090–1096. Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 2012;55:429–436. Bambha K, Wilson LA, Unalp A, Loomba R, Neuschwander-Tetri BA, Brunt EM, et al. Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int 2014;34: 1250–1258. Khalaf N, White D, Kanwal F, Ramsey D, Mittal S, Tavakoli-Tabasi S, et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clin Gastroenterol Hepatol 2015;13:1521–1531 e3. Freedman ND, Everhart JE, Lindsay KL, Ghany MG, Curto TM, Shiffman ML, et al. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology 2009;50:1360–1369. Costentin CE, Roudot-Thoraval F, Zafrani ES, Medkour F, Pawlotsky JM, Mallat A, et al. Association of caffeine intake and histological features of chronic hepatitis C. J Hepatol 2011;54:1123–1129. Hodge A, Lim S, Goh E, Wong O, Marsh P, Knight V, et al. Coffee intake is associated with a lower liver stiffness in patients with non-alcoholic fatty liver disease, hepatitis C, and hepatitis B. Nutrients 2017;9. Ong A, Wong VW, Wong GL, Chan HL. The effect of caffeine and alcohol consumption on liver fibrosis – a study of 1045 Asian hepatitis B patients using transient elastography. Liver Int 2011;31:1047–1053. Liu F, Wang X, Wu G, Chen L, Hu P, Ren H, et al. Coffee consumption decreases risks for hepatic fibrosis and cirrhosis: a meta-analysis. PLoS One 2015;10 e0142457. Yu C, Cao Q, Chen P, Yang S, Deng M, Wang Y, et al. An updated doseresponse meta-analysis of coffee consumption and liver cancer risk. Sci Rep 2016;6:37488. Goh GB, Chow WC, Wang R, Yuan JM, Koh WP. Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study. Hepatology 2014;60:661–669. Setiawan VW, Wilkens LR, Lu SC, Hernandez BY, Le Marchand L, Henderson BE. Association of coffee intake with reduced incidence of liver cancer and death from chronic liver disease in the US multiethnic cohort. Gastroenterology 2015;148:118–125, [Quiz e15]. Ruhl CE, Everhart JE. Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States. Gastroenterology 2005;129:1928–1936. Bamia C, Lagiou P, Jenab M, Trichopoulou A, Fedirko V, Aleksandrova K, et al. Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study. Int J Cancer 2015;136:1899–1908. Huang YQ, Lu X, Min H, Wu QQ, Shi XT, Bian KQ, et al. Green tea and liver cancer risk: A meta-analysis of prospective cohort studies in Asian populations. Nutrition 2016;32:3–8. Alferink LJM, Fittipaldi J, Kiefte-de Jong JC, Taimr P, Hansen BE, Metselaar HJ, et al. Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: the Rotterdam study. J Hepatol 2017;67:339–348. Salomone F, Galvano F, Li Volti G. Molecular bases underlying the hepatoprotective effects of coffee. Nutrients 2017;9. Marventano S, Salomone F, Godos J, Pluchinotta F, Del Rio D, Mistretta A, et al. Coffee and tea consumption in relation with non-alcoholic fatty liver and metabolic syndrome: A systematic review and meta-analysis of observational studies. Clin Nutr 2016;35:1269–1281.
Journal of Hepatology 2017 vol. 67 j 221–223
223
Coffee and tea breaks for liver health Salvatore Petta1,⇑, Giulio Marchesini2 1
Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy; 2Department of Medical and Surgical Sciences (DIMEC), ‘‘Alma Mater” University, Bologna, Italy See Article, pages 339–348
Let food be your medicine (Hippocrates, 400 B. C.) The quality of diet, calorie intake and physical activity/sedentariness are pivotal drivers in the interplay between health and noncommunicable diseases, and the battle against the risks associated with Western-type behaviour is the top priority of medical societies and health institutions. Unfortunately, any attempt at adopting a healthy lifestyle is counteracted by unhealthy environmental pressure, which favours the diseases of affluence, including liver diseases. The typical Mediterranean diet, characterized by the consumption of complex carbohydrates, fibreand antioxidant-rich vegetables, and polyunsaturated fatty acids, is considered the prototype of a healthy diet associated with favourable hepatic outcomes. Unfortunately, this diet is no longer the standard food choice even in the Mediterranean area, where it has largely been replaced by a Western-type diet, rich in saturated fatty acids and sugars, which are associated with a higher risk of metabolic liver disease. In parallel with unhealthy behaviours, there is a larger and larger use of nutraceuticals everywhere. Nutraceuticals are products derived from food sources, supposed to provide medical or health benefits in addition to their nutritional value; they include herbal and plant extracts, vitamins, minerals, amino acids. Their beneficial effects focus on prevention more than cure, with an expanding market with a lot of implications for producers, regulatory agencies, distributors and consumers. Coffee and tea are the most frequently used beverages prepared from plants worldwide; they are consumed primarily for their taste and flavour, but are also considered to be healthy for several organs and tissues, including the liver. Coffee is prepared from the seeds of a plant originally grown in the Arab area in the 15th century and is the second most traded commodity in the world, with lots of varieties and preparations. The consumption of coffee is increasing everywhere, headed by Finnish people with a per capita use of nearly 10 kg seeds/year and over 2.5 cups/day. Tea comes from Southwest China and hundreds of varieties are available as well; it was initially prepared as green tea, with
Received 14 April 2017; accepted 25 April 2017 q DOI of original article: http://dx.doi.org/10.1016/j.jhep.2017.03.013. ⇑ Corresponding author. Address: Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy, Piazza delle Cliniche, 2, 90127 Palermo, Italy. Tel.: +39 091 655 2170; fax +39 091 655 2156. E-mail addresses: [email protected], [email protected] (S. Petta).
the leaves of Camellia Sinensis dipped in hot water, before any oxidation process takes place by fermentation. Contrary to expectations and the long-dated British tradition, Turkey is the country with the largest tea use with 7.5 kg/year per person. Other herbal teas are consumed throughout the world in different amounts, in selected settings and according to specific cultures. Overall, there is some evidence that the consumption of these beverages may confer health benefits. However, it is difficult to support biological plausibility, to provide guidance as to the dose, and some possible warnings about safety should be taken into account.
What is known about coffee, tea and the liver? Several cohort studies assessed the association between coffee intake and the presence/development of non-alcoholic fatty liver disease (NAFLD), or severity of liver damage in patients with chronic liver diseases. The largest study comes from the US and was performed on a cohort of 18,550 individuals.1 After adjusting for clinico-metabolic confounders and other dietary components, the study found a protective effect of caffeine intake on the presence of NAFLD, identified by an unexpected rise of liver enzymes.1 The results have been confirmed in a recent large multi-ethnic study,2 while other studies did not support any association between coffee and both the presence and occurrence of NAFLD.3–5 Conflicting data were also reported on the association between coffee intake and the severity of liver damage in NAFLD patients. Two cross-sectional studies showed that a large amount of coffee was protective towards histologically diagnosed liver fibrosis,6,7 whereas the largest study in this field, in 782 biopsy-proven NAFLD patients, limited the protective effect to patients without insulin resistance, not to the entire cohort.8 In patients with chronic liver disease due to hepatitis C9–11 or hepatitis B2,12,13 viruses or alcohol abuse,14 most studies support a protective effect of coffee drinking on liver damage.9,10,12,14 Finally, solid data are in favour of a beneficial role of coffee use on the risk of hepatocellular carcinoma (HCC), as summarized in a recently updated meta-analysis,15 and of a reduced liverrelated mortality in cohort studies.16,17 In summary, there is some evidence for a beneficial effect of coffee on the liver, with differences possibly due to the baseline characteristics of the populations and to the methods used for estimating coffee drinking and the severity of liver damage.
Journal of Hepatology 2017 vol. 67 j 221–223
Editorial 160
Caffeine amount (mg)
140
140
135
120
120 105
100
100
85 65 60
80
80
80
70
60
57
60
50
45 40 35
40
32
35
20
35
20
20
48 39
41
30
26
20 10
10
e (3 rgy 30 dr m ink l) s
En
ga (3 r-fr 30 ee m co l) la
Su
C o (3 la d 30 rin m ks l)
Ye r (3 ba 30 m m ate l)
G r (1 een 50 t m ea l)
Ic (3 ed 30 te m a l)
T (1 ea 50 ba m g l)
pr e (3 sso 0 m c of l) fe e
Es
lu (1 ble 25 co m ffe l) e
So
Fi
lte (1 red 25 co m ffe l) e
0
Fig. 1. Sources of caffeine and amount per serving in coffee, tea and other beverages. Data are expressed as minimum, maximum and average (in red), according to different preparations and brands. Redrawn and modified from data of the Institute for Scientific Information on Coffee (www.coffeeandhealth.org). Note that the amount of caffeine in decaffeinated coffee and hot chocolate is negligible (\10 mg/serving).
On the contrary, only limited and not univocal evidence is available on the interplay between liver and tea consumption. As part of the NHANES I Epidemiologic Follow-up Study, a 20-year follow-up study including nearly 10,000 participants, drinking coffee and tea together decreased the cumulative incidence of chronic liver disease, particularly in subjects at higher risk of liver disease, but no separate analysis on tea consumption was provided.18 In patients with HCV infection, tea consumption did not show any significant effect on liver outcomes,10 while caffeinated tea drinking in non-coffee consumers was associated with a reduced risk of advanced fibrosis.9 Two Western studies reported contrasting results about the impact of tea drinking and HCC occurrence,17,19 while a recent meta-analysis largely involving Asian populations reported a protective effect of green tea against HCC occurrence.20 Finally, cohort studies did not show any positive effect of both black and green tea on liver-related death.17,18 What is new? In the present issue of the Journal, Alfering et al.21 report on the association of both coffee and tea drinking with the presence of steatosis and fibrosis in a cohort of 2,424 individuals from the Rotterdam study – an ongoing population-based cohort study. Ultrasonography-assessed steatosis was present in about 30% of the individuals; clinically relevant hepatic fibrosis, estimated by FibroScan, was present in 5%. Notably, drinking 3 or more cups of coffee per day, compared with no coffee, was protective against clinically relevant fibrosis, and both coffee and herbal tea consumption were independently associated with log-transformed liver stiffness. Finally, no association was found between either coffee or tea drinking and the presence of steatosis. These results are in keeping with those reported in a much smaller study, where fibrosis was tested by a patented test (FibroTest).4 The study by Alfering et al. qualifies as the largest study ever reported on the relationship between coffee, tea and liver health in a general population, the only one also reporting on tea intake,
222
and measuring the severity of fibrosis by a reliable, widely available method, i.e. liver stiffness by FibroScan. In addition, all results were confirmed after adjusting for different demographic, clinical and metabolic risk factors as well as for calorie intake and other nutrients. The beneficial effect of coffee on liver fibrosis increased after adjusting for confounders, suggesting that big coffee consumers also have unhealthy lifestyles, it was more pronounced in the subgroup of patients with fatty liver, and was also confirmed in patients with normal ALT and in subgroups where the food frequency questionnaire was either administrated at the time of liver evaluation or 5.8 years before. Finally, in the analysis of tea intake, the study not only considered overall tea intake, but also took into account the potentially different effect of black, green and herbal tea on liver outcomes. These are the main strengths of the study, but the results should be interpreted with caution as: 1) the study is limited to an elderly Caucasian population (mean age, 66 years); 2) the prevalence of coffee consumers is very high (93%), so big coffee consumers – the cohort protected from severe liver fibrosis – are compared to a very small group of individuals; 3) the prevalence of tea consumers is also high (85%), but the amount of tea intake is low, thus underestimating a potential protective effect of tea and especially of green tea, as reported in Asian populations; and 4) the lack of any effect of both tea and coffee on hepatic steatosis, already reported in the literature, might depend on the scarce sensitivity of ultrasonography. As a common concluding remark, the authors suggest that further studies using more objective non-invasive tools, like controlled attenuation parameter, are needed to define this issue. In our opinion a more pressing question remains before the results may be turned into recommendations, as detailed below. How can we explain the biological effects of coffee and tea on the liver? More than 100 components are present in coffee and tea, including polyphenols and caffeine, which are contained in both beverages in very different and variable amounts. Notably, caffeine content
Journal of Hepatology 2017 vol. 67 j 221–223
JOURNAL OF HEPATOLOGY may be very high in a few green tea brands, totally absent in a few herbal teas (as an example, Chamomile tea) and both caffeine and polyphenols are also present in several edulcorated drinks associated with the obesity epidemics and NAFLD (Fig. 1). Experimental data, reviewed by Salamone et al.22 showed that caffeine inhibits hepatic stellate cell proliferation, thus exerting an anti-fibrogenic effect via adenosine receptor blockade. In addition, caffeine was reported to have haemodynamic effects in a rat model of portal hypertension, decreasing portal pressure, porto-systemic shunting and hepatic angiogenesis. Polyphenols, namely chlorogenic acid, have a potent antioxidant, anti-inflammatory and hepatoprotective effect independent of caffeine,22 and synergistically act with caffeine on fibrosis development. However, the amount and quality of polyphenols and related antioxidant components is dependent on coffee, tea and herbal tea varieties and by the method of preparation, and might be the basis to explain the variable positive effects on hepatic fibrosis.22 While the protective effects of both coffee and tea on liver fibrosis are supported by both epidemiological and experimental evidence, conflicting results are available on the association with fatty liver. A recent meta-analysis reported a protective effect of both coffee and tea on the risk of the metabolic syndrome;23 experimental studies suggested a modest antisteatogenic effect of both beverages,22 but clinical studies were negative.2–5 Thus, in the complex human model, coffee and tea might in part prevent fatty liver, but are more likely to act as moderators of the detrimental effect of second hits, leading to inflammation and fibrosis.
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Conclusions There is an increased interest in diet and nutrition in liver diseases. A balanced diet, mostly resembling the Mediterranean diet, remains the cornerstone to reduce obesity and the risk of metabolic liver disease, and in patients with chronic liver diseases, to reduce the risk of complications, irrespective of aetiology. Should we add regular coffee and tea breaks to our daily life? Before this policy can be recommended, prospective studies are needed to identify the optimum amounts and the type(s) of coffee and tea leading to more favourable liver outcomes. Nutraceuticals are largely used with several indications without any convincing evidence; the risk of rare but severe liver toxicity associated with green tea use, as well as the cardiovascular effects of caffeine, should not be forgotten before supporting a diffuse implementation of these beverages.
[15]
[16]
[17]
[18]
[19]
[20]
References [21] [1] Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012;35:76–82. [2] Setiawan VW, Porcel J, Wei P, Stram DO, Noureddin N, Lu SC, et al. Coffee drinking and alcoholic and nonalcoholic fatty liver diseases and viral hepatitis in the multiethnic cohort. Clin Gastroenterol Hepatol 2017. http://dx.doi.org/10.1016/j.cgh.2017.02.038. [3] Gutierrez-Grobe Y, Chavez-Tapia N, Sanchez-Valle V, Gavilanes-Espinar JG, Ponciano-Rodriguez G, Uribe M, et al. High coffee intake is associated with
[22] [23]
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