October 22, 2013

Can Daily Coffee Consumption Reduce Liver Disease–Related Mortality?

Clinical Gastroenterology and Hepatology
Volume 11, Issue 11 , Pages 1422-1423, November 2013

Vivian Ng, MD, Sammy Saab, MD, MPH, AGAF

published online 01 July 2013.

Because of widespread skepticism regarding the safety of Western medication, there is great interest in studying alternative treatments that are considered natural and safe from toxicities.1 Many foods and diets are believed to promote health and longevity.2 Coffee is a beverage with a distinct taste and aroma that commonly is consumed throughout the world and is being assessed for its potential health benefits.3 For instance, a decreased risk of type 2 diabetes, heart disease, and stroke has been described in regular coffee drinkers.4, 5, 6 In a recent analysis of the National Institutes of Health–AARP Diet and Health Study data published by Freedman et al,7 the investigators described a dose-dependent inverse association between coffee consumption and total mortality.

Chronic liver disease is a major health burden in the United States.8 Treatment for many causes of liver disease is limited by significant adverse effects or a lack of efficacious medications.9 There has been increasing interest in the hepatoprotective properties of coffee consumption.10 Coffee consumption has been observed to have an inverse association with serum levels of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase.11, 12 In a large cross-sectional US study, intake of regular ground coffee and caffeine intake was associated with a decreased risk of progression of chronic liver disease.13 Those who drank more than 2 cups of coffee daily over a median follow-up period of 19 years had less than half the rate of chronic liver disease than those who drank less than 1 cup daily. A decreased rate of hepatic fibrosis progression was described in patients who consumed more than 2 cups of caffeinated coffee by Modi et al (odds ratio, 0.33; 95% confidence interval [CI], 0.14–0.8; P = .015).14 Not only has coffee been associated with a decrease in a number of liver diseases, but its consumption also may decrease liver-related mortality.7

In this issue of Clinical Gastroenterology and Hepatology, Bravi et al15 performed a meta-analysis examining the relation between coffee consumption and the risk of developing hepatocellular carcinoma (HCC). This study was performed as an update to their previous meta-analysis that was published in 2007.16 The current meta-analysis combined the results from 16 studies, 8 of which were case-cohort studies and the other 8 were case-control studies. The total number of cases combined from the 16 studies was 3153 patients with HCC. The investigators found that the summary relative risk (RR) of developing HCC with coffee consumption was 0.60 (95% CI, 0.50–0.71) overall. The data were stratified further according to the amount of coffee consumption. The summary RR was 0.72 (95% CI, 0.61–0.84) based on 14 studies comparing low coffee consumption vs no coffee consumption. The summary RR was 0.44 (95% CI, 0.39–0.50) overall high coffee consumption vs no consumption. From the data, the investigators extrapolated that the RR estimate for each extra cup of coffee consumed daily was 0.80 (95% CI, 0.77–0.84). The investigators showed an inverse relation between coffee consumption and HCC risk, even when stratifying for sex, alcohol use, or cause of underlying liver disease. The HCC-specific action is highlighted further by the negative association reported by another study of pancreatic cancer in this issue.17

Although the results are promising that coffee consumption has an inverse relation to the development of HCC, applying these results to daily practice still may yet be elusive. Additional work is needed to identify which specific component of coffee is the contributing factor in reducing liver disease and related mortality. Although the main compounds in coffee implicated to have protective roles in the liver are caffeine and chlorogenic acid, there are more than 1000 compounds that could be responsible for its beneficial effects.18 Caffeine is thought to play a role in protecting against hepatic fibrosis. One mechanism, proposed by Gressner,19 is that caffeine plays a role in the degradation of Smad2 and Smad3 proteins, which are mediator proteins of transforming growth factor β, a profibrogenic signaling pathway. Caffeine also is thought to affect the hepatic detoxification process by activating uridine 5′-diphospho-glucuronosyltransferase.20 Coffee-specific diterpenes, kahweol and cafestol, also may confer hepatoprotective effects via activation of the cis-acting antioxidant-responsive element sequence21 (Table 1).

Table 1. Bioactive Compounds in Coffee With Potential Health Benefits
Compound Composition Proposed hepatoprotective mechanism
Caffeine Purine alkaloid antagonizes A1 and A2A subtypes of the adenosine receptor Modifies TGF-β pathway to decrease liver fibrosis19
Hepatic detoxification via activation of uridine 5′-diphospho-glucuronosyltransferase20
Cafestol and kahweol Fat-soluble diterpenes typically are removed from coffee by paper filters Activates the cis-acting antioxidant-responsive element sequence21
Chlorogenic acids Esters are formed between quinic and trans-cinnamic acids, an important group of dietary phenols Antioxidant activity in vitro, metabolized in colon
Exact mechanism unknown

TGF, transforming growth factor.

Other commonly consumed beverages also have been studied for their effect on chronic liver disease. In a study examining the relationship between coffee and tea consumption with the incidence of death or hospitalization from chronic liver disease, regular coffee consumption was associated with less than half the rate of liver disease than in patients who drank no coffee, or in patients who drank decaffeinated coffee. Decaffeinated coffee did not have the same hepatoprotective effects when compared with regular coffee, with a multivariate-adjusted hazard ratio of 1.3 (95% CI, 0.58–3.0) vs 0.5 (95% CI, 0.27–1.0).13 When studying the effect on HCC, there was a decreased risk of HCC with increasing coffee consumption, but no significant associations were seen with decaffeinated coffee or tea.22, 23

Coffee consumption is not without potential conflicts. Coffee ingestion can have immediate effects, such as feeling jittery, and also has systemic cardiovascular effects, such as increasing blood pressure and heart rate.24 Daily consumption of caffeinated beverages also can lead to physical dependence. Discontinuation of caffeine intake can lead to withdrawal symptoms such as headache, fatigue, difficulty with concentration and memory, and mood disturbances.25 This potentially can be significantly debilitating because patients with chronic liver disease already often suffer from fatigue, depression, and memory changes.26

There are numerous limitations when interpreting the studies regarding the health benefits of coffee. The lack of standardization of coffee preparations and serving sizes among various studies leads to ambiguity regarding how much coffee intake is necessary for these effects to be seen. The duration of coffee consumption to yield a protective effect is also unknown. Although the aforementioned studies provide compelling evidence to suggest that coffee is useful as an adjunct treatment of liver disease in reducing the risk of HCC, further trials would need to be performed to provide evidence for causation, to eliminate confounding variables, and to determine an acceptable standardized dose and preparation of coffee needed to see hepatoprotective effects. Nevertheless, coffee is relatively inexpensive and readily available. The data from Bravi et al16 indeed illustrate that coffee consumption is associated with a decreased risk of HCC in an elegant meta-analysis of the literature. Patients at risk of HCC should be encouraged to continue consuming coffee if they already are doing so. Coffee-naive patients should consider the risks and benefits before recommendations are made to start drinking coffee.


Conflicts of interest The authors disclose no conflicts.

PII: S1542-3565(13)00882-3


© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Refers to article:

Coffee Reduces Risk for Hepatocellular Carcinoma: An Updated Meta-analysis , 08 May 2013 Francesca Bravi, Cristina Bosetti, Alessandra Tavani, Silvano Gallus, Carlo La Vecchia

Clinical Gastroenterology and Hepatology November 2013 (Vol. 11, Issue 11, Pages 1413-1421.e1)Abstract Full Text PDF (1475 KB)


1 comment:

  1. This is a nice intelligent analysis. I can add a couple of items; chlorogenic acid decreases hepatic TLR4 sensitivity, and caffiene antagonises adenosine, which is a DAMP stop signal for HSCs (the presence of adenosine from damaged cells tells HSCs when to stop at the end of chemotaxis).
    It always amuses me that peer reviewers accept pro-caffeine research without screening out authors who are addicted to the drug!