Wednesday, August 14, 2013

Impact of Coffee on Liver Diseases: A Systematic Review

Impact of Coffee on Liver Diseases: A Systematic Review

In this recent systematic review offered online at Liver International, researchers investigated several studies assessing the effect of coffee on liver disease.

The abstract, introduction and discussion "only" are provided below, the complete review article is available online in Liver International found in Accepted Articles. Download the PDF here.  
In addition, posted today over at Healio is an easy to read summary of the article: Studies indicate protective effects of coffee for liver disease
Impact of Coffee on Liver Diseases: A Systematic Review
Liver International

Accepted Article
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record.

Please cite this article as doi: 10.1111/liv.12303
This article is protected by copyright.
All rights reserved.

Received Date : 03-Jun-2013
Revised Date : 05-Aug-2013
Accepted Date : 05-Aug-2013

Article type:
Reviews Impact of Coffee on Liver Diseases: A Systematic Review

Sammy Saab, MD, MPH, AGAF, 1,2 Divya Mallam, MD, 3 Gerald A. Cox II, BA, 2 Myron Tong, PhD, MD 1,2,4 Departments of Medicine 1 and Surgery 2 , David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California, The Department of Medicine, Harbor-UCLA Medical Center 3 , Torrance, California, and the Huntington Medical Research Institutes, Pasadena, California

Accepted manuscript online: 12 AUG 2013

Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed.

Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. More over, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

Introduction Only

Coffee is a commonly consumed beverage worldwide. In the United States, over 50% of Americans consume coffee on a daily basis. 1 The commonly cited reasons for coffee consumption are its stimulatory effects, taste and aroma. 2, 3 Recent data suggests that coffee consumption may have health benefits in a number of medical ailments. Long-term coffee drinkers may be at a decrease risk for type II diabetes, symptomatic gallstone disease, Parkinson’s disease, heart disease and stroke. 2, 4-7 Moreover, coffee consumption is associated with decreased all-cause mortality. 8, 9 In a recent analysis of the NIH- AARP Diet and Health Study data, a dose-dependent inverse association between coffee consumption and total mortality was described. 9 Men and women who drank 6 or more cups daily had a 10% and 15% decreased risk of death, respectively.

Chronic liver disease is major health burden in the United States, ranking 12 th amongst the leading causes of death and accounting for over 30,000 deaths in 2009 alone. 10 Chronic liver disease affects approximately 15% of the U.S. population and is a major economic strain through direct healthcare expenditures as well by indirect costs related to lost income due to premature death or disability. 11, 12 Treatments for liver disease is often viewed with suspicion, and many patients often seek alternative therapies for their liver disorders. 13-1

Given the potential health benefits in a variety of medical conditions and its impact on survival, we explored the impact of coffee consumption on patients with liver ailments. A systematic, comprehensive review on the interaction between coffee consumption and liver associated tests, viral hepatitis, nonalcoholic Fatty Liver Disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed and is presented herein.

Discussion Only

Coffee is one of the most commonly consumed beverages in the world. 2 There is increasing evidence that daily consumption of 2-3 cups of coffee has significant health benefits. Not only has coffee been associated with a decrease in a number of liver diseases, but its consumption may also decrease mortality. 9 Thus, coffee appears to have ‘hepatoprotective” health benefits. 64 Coffee is composed of over one hundred compounds, any of which could be responsible for its beneficial effects. 46 It is possible not one compound in particular, but the synergistic effect of multiple compounds, which provides the health benefits described.

Not all types of coffee may be beneficial in liver disease. Numerous studies have shown a hepatoprotective role for filtered coffee, and a potentially deleterious effect for unfiltered coffee. 24, 65 It was postulated that this difference is due to the presence of kahweol and cafestol, which are caffeine diterpenes that are released from ground coffee beans but removed by paper filters. 65, 66 Moreover, another study found that espresso coffee had no beneficial effect on liver disease, particularly in NAFLD. 46 In the U.S, filtered coffee is one of the main types of coffee consumed, whereas in Europe, espresso coffee is more commonly consumed. 46 Anty et  al postulated that perhaps espresso coffee was not found to be beneficial in NAFLD because of the sucrose added to the coffee. 46 Sucrose is composed of glucose and fructose, and fructose has been associated with increased severity of hepatic fibrosis in NASH. 7

There are a number of proposed mechanisms for the hepatoprotective effects of caffeine (Table 6). In rat studies, methylxanthine caffeine has been implicated in the hepatic fibrinogenesis pathway by (1) downregulating transforming growth factor beta-1 (TGFB-1)-induced connective tissue growth factor (CTGF) production in hepatocytes via promotion of breakdown of SMAD2 (a TGF-B effector protein), (2) inhibition of SMAD3 phosphorylation, and (3), by upregulation of the PPAR-gamma receptor. 67 The antioxidant hepatoprotective effects of coffee may also be induced by UDP glucoronosyltransferases (UGT1A). 68 Caffeine has also been implicated to have antifibrotic effects via its influence on hepatic stellate cells (HSC) through inhibition of focal adhesion kinase (FAK) and actin synthesis, stimulation of HSC apoptosis, induction of intracellular F-actin and cAMP expression, and via inhibition of procollagen type 1C and alpha-smooth muscle actin (SMA) expression. 69

Caffeine as well as cafestol and kahweol may have anticarcinogenic effects by upregulation of (ARE)-regulating signaling (Table 6). 70, 71 The antioxidant-responsive element (ARE) sequence plays a key role in carcinogenesis as it has been found on the promoter of numerous genes involved in detoxification processes. Furthermore, animal models and in-vitro studies indicate that kahweol and cafestol may deregulate enzymes involv ed in detoxification of carcinogens. 72, 73 These compounds also induce glutathione-S-transferase (GST) and gamma-glutamylcysteine synthetase (GCS), leading to protection against mutagenesis, and inhibit N-acetyltransferase. 75

Although caffeine is a major component of coffee, studies evaluating non-coffee caffeinated sources have revealed inconsistent evidence of hepatoprotective effects. 29, 26 With regards to tea consumption, studies have found no statistically significant association between tea intake and risk of cirrhosis, 30, 29 death from cirrhosis, 32 chronic liver disease, 28 HCC, 54 or death due to HCC. 77, 60, 52 Most studies did not specify which type of tea participants consumed. However, Inoue et al studied green tea and Kurozawa et al studied green, black, and oolong tea. 56, 60

Coffee preparation methods include filtered, unfiltered, and espresso, and can also vary in its roast profile (medium vs. dark). Differences in prep aration method (filtered, unfiltered, espresso) as well as type of roast play a role in the composition of coffee. Filtered coffee does not contain cafestol and kahweol; however, filtration of coffee better preserves chlorogenic acids than the barista method of espresso preparation. 46 The various degrees of roast refer to the internal bean temperatures found during roasting. Darker roasts have had higher roasting temperatures. Caffeine content also varies between types of coffee [generic brewed coffee (95-200 mg per 8 oz), espresso (40-75 mg per 1 oz), generic instant coffee (27-173 per 8 oz)].

There are numerous limitations when interpreting the studies regarding the health benefits of coffee. Many of the larger studies, including those by Freedman et al, Modi et al, Hu et al, and Molloy et al, did not necessarily account for differences in socioeconomic status or other dietary factors. 38, 27, 57, 45 Although one would argue that perhaps patients who had greater coffee intake were likely healthier, Freedman et al found that coffee drinkers tended to have poorer overall health (p= 0.29) and vitality scores (p=0.018) compared to non-coffee drinkers. In addition, participants who drank coffee may have had higher cigarette use and alcohol consumption. 38 Also, many studies collected data on coffee intake at only one time point, thus, the coffee intake noted may not have accurately reflected participants’ intake over time. 26, 30, 32- 34 If it is assumed that caffeine is indeed responsible for the hepatoprotective effects of coffee, then another potential limitation is the variation of caffeine content of coffee within and among coffee shops. 77 Furthermore, many studies failed to define coffee cup size. 22, 26, 29,32 Although it is clear that coffee intake has hepatoprotective effects, the lack of standardization of coffee cup size amongst various studies leads to ambiguity regarding how much coffee intake is necessary for these effects.

Our study is limited in that it is based mostly upon observational studies with inherent biases, including recall bias in retrospective studies, as well as selection bias and unmeasurable confounding factors amongst all non-randomized controlled studies. 79 Cross-sectional studies, such as NHANES III, are limited in that they cannot establish a temporal association between coffee intake and study findings. 26,79

Numerous epidemiological studies suggest that consumption of approximately 3 or more cups of coffee daily will reduce the risk for and severity of hepatotoxicity due to a variety of underlying pathologic processes. While the aforementioned studies provide comp elling evidence to suggest that coffee is useful as an alternative medicine in the treatment of the most common types of liver disease, blinded randomized controlled trials must be performed to provide evidence for causation, and to eliminate confounding variables and various types of bias inherent in cross-sectional, cohort, and case- control studies. Additional animal and cell culture studies are also warranted to further elucidate the biochemical basis for the potential beneficial effects of coffee in liver disease patients.

• Coffee is one of the most commonly consumed beverage.
• The beneficial impact of coffee consumption on liver related complications are not well understood or appreciated.

• Liver enzymes are lower in patients who regularly consume coffee
• Coffee consumption associated with decreased hepatitis C fibrosis progression.
• The risk of hepatocellular carcinoma is decreased in consumers of coffee.

Full text available online in Liver International
Download PDF here....

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