10 September 2013
Hepatitis C: Unexpected results from a clinical trial of coffee
Germs such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and injure the liver. Long-term or chronic infection with either of these viruses can cause inflammation and healthy liver tissue is replaced with useless scar tissue. Prolonged increased levels of liver enzymes in the blood occur, suggestive of ongoing liver injury. Gradually the liver becomes increasingly dysfunctional and serious complications develop. As liver injury spreads throughout this organ, the risk of some liver cells developing abnormally and transforming into pre-cancer and cancer increases.
Testing for HCV infection and regular medical monitoring and discussion of treatment options among infected people are important steps. Successful treatment for HCV can cure this viral infection, normalize liver enzyme levels and greatly reduce the risk of developing liver cancer.
Coffee and chocolate research
Coffee and chocolate (as well as many colourful fruits and vegetables) contain compounds called flavonols. In laboratory experiments with cells, these compounds can help reduce inflammation.
In the past decade, results from observational studies suggest that regular consumption of coffee appears to benefit the liver. Different studies have reported different but related findings, such as decreased levels of liver enzymes, reduced scarring of the liver and even a lowered risk for developing liver cancer.
A recent observational study in France suggests that daily consumption of coffee and chocolate is associated with having normal liver enzyme levels in participants who were co-infected with HIV and HCV.
It is important to note that many of the promising findings reported from coffee drinking and its impact on liver health come from observational studies. Such studies are good at finding associations but can never prove cause and effect. In other words, observational studies can never prove that drinking coffee leads to improved liver health. This problem with observational studies arises from built-in design limitations.
Therefore, findings from observational studies must be treated cautiously. Ideally such findings should be explored in clinical trials of a more robust statistical design.
A randomized trial
In an attempt to provide clarity around the possible benefits of coffee for liver health, a research team at Padua University in Italy conducted a relatively small and short randomized clinical trial among participants with HCV infection. The researchers found that levels of some liver enzymes rose while others fell during coffee consumption. However, these changes were relatively small. Levels of HCV rose with coffee consumption, while blood tests suggested decreased scarring in the liver. These unexpected findings are discussed later in this CATIE News bulletin.
Researchers recruited volunteers with HCV infection who had undergone a liver biopsy in the recent past. The results of the biopsy proved that they had HCV-related liver injury. No participant was undergoing therapy for HCV infection while in the study.
Participants were randomly assigned to one of the two following interventions:
- four cups of coffee daily for one month
- no coffee for one month
At the end of the first month, participants switched assignments; the technical term is that they crossed over. That is, those who were previously drinking coffee stopped and vice versa.
All participants received an Italian-style coffee machine—Moka, made by Bialetti—and enough coffee to make four cups daily during the month that coffee intake was required.
The researchers supplied coffee that was commonly available in their region and it was 100% Arabica. They also had samples of this coffee independently analysed to confirm the flavonol content.
At the start of the study, the average profile of the 37 participants was as follows:
- 29 men, 8 women
- age – 58 years
- 70% had a subtype or strain of HCV called genotype 1
- 22% smoked tobacco
- 46% normally drank either none or up to two cups of coffee daily
- 54% normally drank between three and five cups daily
- most participants had a mild-to-moderate degree of liver injury caused by HCV
Prior to initiating the study protocol, researchers analysed blood samples from participants and found that volunteers who regularly drank four cups of coffee daily generally had lower levels of liver enzymes than people who drank no coffee or up to two cups of coffee daily.
Results—At the end of the study
Most participants stated that their adherence to the study protocol was very good.
Here are key results distributed according to coffee usage:
Differences in the levels of the liver enzyme AST (aspartate aminotransferase)
- coffee – 69 Units/Litre
- no coffee – 63 U/L
Differences in the levels of the liver enzyme GGT (gamma-glutamyl-transferase)
- coffee – 55 U/L
- no coffee – 63 U/L
Marker of oxidative damage
- coffee – 15
- no coffee – 63
HCV viral load
- coffee – 790,000 IU/ml
- no coffee – 480,000 IU/ml
Marker of programmed cell death (apoptosis) in the blood
- coffee – 712 U/L
- no coffee – 649 U/L
Marker of liver fibrosis (pro-collagen type III)
- coffee – 56 ng/mL
- no coffee – 86 ng/mL
All of these differences in various tests between the periods when participants drank coffee and were abstinent were statistically significant.
Points to consider
Overall, the level of the liver enzyme GGT in the blood fell slightly while levels of the liver enzyme AST rose slightly. HCV viral load rose with coffee intake.
These findings were unexpected. However, the researchers noted that the changes in liver enzyme levels were “limited” and not clinically relevant. Also, the rise in HCV viral load was less than the level usually considered clinically meaningful—1 log.
The reduction in blood levels of the marker pro-collagen type III when participants drank coffee suggests that less collagen was deposited in the liver. This change may, in part, explain reports of a reduced rate of liver damage in other studies of fatty liver disease. However, neither liver biopsies nor specialized ultrasound scans of the liver (Fibroscan) were done to confirm possible changes in fibrosis.
Bear in mind
The present study’s findings, although drawn from a randomized crossover clinical trial design, should be seen as preliminary and a good first step on the path to better understanding the impact of coffee on liver health.
The trial was imperfect and was relatively short—two months in length. Furthermore, the ability of participants to adhere to the study protocol was self-reported and not independently confirmed.
The Italian researchers need to be supported for launching the bold and time-consuming step of conducting a prospective randomized clinical trial. Its results should serve as a foundation for testing coffee and/or chocolate consumption in HCV-positive people with different degrees of liver damage.
At a minimum, other research teams need to repeat the Italian clinical trial, perhaps exploring the effect of different methods of preparing coffee (regular vs. expresso), as observational studies have yielded conflicting results. Hopefully, such future trials will be bigger, longer and more complex, producing helpful information about the possible benefits of coffee and its ingredients. Future prospective randomized studies also need to investigate chocolate consumption as a recent French observational study suggests that it might be beneficial in people who are co-infected with HIV and HCV.
Coffee and chocolate are not a substitute for regular checkups, medical monitoring and treatment in people with liver damage caused by hepatitis C or other viruses. Future prospective research is needed to show exactly how coffee and chocolate might help people with liver injury that arises from viral hepatitis or other causes.
hepcinfo.ca – CATIE’s hepatitis C website
—Sean R. Hosein
- Patrizia Carrieri M, Lions C, et al. Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13 HEPAVIH cohort study. Journal of Hepatology. 2013; in press.
- Lai GY, Weinstein SJ, Albanes D, et al. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers. British Journal of Cancer. 2013; in press.
- Costentin CE, Roudot-Thoraval F, Zafrani ES, et al. Association of caffeine intake and histological features of chronic hepatitis C. Journal of Hepatology. 2011 Jun;54(6):1123-9.
- Trovato GM, Martines GF, Trovato FM, et al. Regular coffee: a magic bullet or a naked gun? Regular coffee but not espresso drinking is protective against fibrosis in NAFLD. Journal of Hepatology. 2013 Jun;58(6):1264-5.
- Anty R, Marjoux S, Iannelli A, 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. Journal of Hepatology. 2012 Nov;57(5):1090-6.
- Molloy JW, Calcagno CJ, Williams CD, et al. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology. 2012 Feb;55(2):429-36.
- Cardin R, Piciocchi M, Martines D, et al. Effects of coffee consumption in chronic hepatitis C: a randomized controlled trial. Digestive and Liver Disease. 2013 Jun;45(6):499-504.