Coffee Decreases HCV Advanced Fibrosis Risk

Posted on June 7, 2015

New study indicates that an average daily intake of an estimated 100 mg of caffeine from coffee, tea, or soda is associated with an approximately one-third reduction in odds of advanced fibrosis, although higher intake does not seem to confer any additional benefit. Interestingly, tea intake in those who do not consume coffee may also be associated with a decreased risk of advanced fibrosis. Study authors noted an average of 100 mg or more of caffeine daily from sodas and teas does not have the same protective effect as 100 mg or more of caffeine daily from combined sources (coffee, tea, soda) or from coffee alone, suggesting that caffeine alone may not entirely explain the effect of coffee on liver disease.

A number of studies have indicated that coffee may be protective against the development of liver injury, as manifested by abnormal liver function tests and/or cirrhosis from a variety of hepatic parenchymal disorders. An inverse association between coffee consumption and hepatocellular carcinoma (HCC) in both the presence and absence of chronic hepatitis C virus (HCV) infection has been reported in several meta-analyses of case–control and cohort studies. Caffeine may account for the hepatoprotective effects of coffee in HCV-related chronic liver disease. The results of questionnaire-based study to further investigate the possible association between caffeinated and decaffeinated coffee, tea, and soda, and the development of HCV-related advanced liver fibrosis, were recently published online in the journal Clinical Gastroenterology and Hepatology. (Khalaf N, et al. Clin Gastroenterol Hepatol. 2015 Mar 14[Epub ahead of print]).

Data for this analysis came from a large cross-sectional, study among US veterans (18 to 70 years) with chronic HCV infection, who were prospectively recruited from a dedicated HCV clinic at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, between January 5, 2009, and November 30, 2013. Those with a self-reported or medical record–reported history of liver transplant, decompensated liver disease, or HCC, were excluded from the study.

  • Veterans were asked about their lifetime history of alcohol, tobacco, injection drug use (IDU), marijuana use, other recreational drug use, and the presence of comorbid conditions, including diabetes mellitus.
  • Veterans were also asked about their average daily intake of coffee, tea, and soda in the year preceding study recruitment. Cumulative lifetime exposure to coffee was assessed by asking about daily intake in each decade of life starting in the 20s.
  • Total caffeine intake was calculated from the sum of reported daily intake from all sources, and further stratified as caffeine from coffee and non-coffee sources.
    • Average caffeine content was estimated as follows: 137 mg for each 8-oz cup of coffee, 30 mg for each 8-oz cup of tea, 46 mg for each 12-oz can of caffeinated soda, and 0 mg for each cup or can of a decaffeinated beverage.
  • Degree of hepatic fibrosis and inflammation was determined using the FibroSURE test.

All 910 enrolled Veterans had detectable HCV RNA levels at the time of the study and none were actively receiving treatment. Most participants were male (97.6%), African American (54.2%), and chronic alcohol users (54.2%), with no significant differences between study cases and controls.

  • Cases: 342 (37.6%) patients with advanced fibrosis (F3/F4–F4)
  • Controls: 568 (62.4%) patients with mild fibrosis (F0–F3).

Advanced fibrosis cases were significantly older (average, 1.8 y), had higher BMIs, and were more likely to have type 2 diabetes mellitus and metabolic syndrome, compared with the mild fibrosis controls. Among nondiabetic participants, advanced fibrosis cases were more likely than controls to be insulin-resistant based on a baseline fasting HOMA-IR score of 3 or higher. Cases were more likely to have higher Model for End-Stage Liver Disease (MELD) scores (>9) and to have received prior HCV antiviral therapy than controls. Marijuana use, IDU, level of physical activity, and smoking history were not significantly different between cases and controls.

Most participants (54.6%) reported drinking some caffeinated coffee within the year preceding study enrollment, with 47.2% drinking on average 1 or more cups per day. In contrast, few participants (<8%) reported decaffeinated coffee use, with less than 5% reporting an average intake of 1 or more cups per day.

Mild fibrosis controls had a higher average daily intake of caffeinated coffee compared with advanced fibrosis cases (mean, 1.37 vs 1.05 cups/d; P = 0.038), and were more likely to drink an average of 1 or more cups of caffeinated coffee daily (49.8% vs 43.0%; P = 0.045).

  • Decaffeinated coffee intake was not different between the groups.
  • The average daily intake of coffee in prior life decades was higher in mild fibrosis controls than in advanced fibrosis cases, but none of these differences reached statistical significance.
  • Overall, caffeinated and decaffeinated tea intake (hot or iced) within the prior year was not notably different between advanced fibrosis cases and mild fibrosis controls.

Among the subset of non–coffee drinkers (n = 413), caffeinated tea use was more common among mild fibrosis controls than advanced fibrosis cases (26.2% vs 17.0%; P = 0.030).

Mild fibrosis controls more frequently reported an average caffeinated soda intake of 1 or more cans daily compared with advanced fibrosis cases (40.5% vs 32.5%; P = 0.015).

  • Among the subset of non–coffee drinkers (n = 413), intake of 1 or more cans daily of caffeinated soda use was not significant (37.9% vs 33.9%; P = 0.412).
  • There was no notable difference in decaffeinated soda intake between cases and controls.

Although quite variable, daily caffeine consumption from all beverages (coffee, tea, and soda) was, on average, higher in mild fibrosis controls than in advanced fibrosis cases (273.8 vs 218.2 mg; P = 0.013). The majority of caffeine consumption in both groups came from coffee, with controls having a higher percentage of their daily caffeine consumption derived from coffee sources.

  • While a total combined caffeine intake or dose of 100 mg or more daily appeared to be associated with a significant decrease in risk of hepatic fibrosis, no further risk reduction was observed with higher coffee or caffeine doses.
  • After excluding coffee drinkers, an intake of 100 mg or more and 200 mg or more of caffeine daily from non-coffee sources (tea and soda) was slightly higher in mild fibrosis controls than in advanced fibrosis cases, but the difference was not significant.

A daily average intake of 100 mg or more and 200 mg or more of caffeine from all sources was associated with a significantly reduced risk of advanced fibrosis (P = 0.014 and P = 0.045, respectively).

  • The inverse association between 100 mg or more of caffeine intake daily and advanced hepatic fibrosis remained significant after adjustment for potential confounders (eg, age, alcohol use, BMI, MELD score, and metabolic syndrome), and was attenuated when adjusted for HOMA-IR status.

The hepatoprotective effects of an average daily intake of 100 mg or more of caffeine (adjusted odds ratio, 0.71; 95% confidence interval, 0.53–0.95; P = 0.020) and 1 cup or more of caffeinated tea by non–coffee drinkers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34–0.94; P = 0.028) persisted after adjustment for confounders, including insulin resistance.

Insulin resistance has been shown to worsen hepatic inflammation in patients with HCV. Based on FibroSURE scoring, 252 participants (27.7%) in this study were classified as advanced inflammatory activity cases (A2/A3–A3), and 658 (72.3%) were classified as mild inflammatory activity controls (A0–A2).

  • There was no significant association between caffeine intake from coffee, tea, or soda in the year preceding study enrollment and severity of hepatic inflammation

This study indicates that self-reported coffee drinking and caffeine consumption from beverages were associated with a lower risk of advanced hepatic fibrosis in patients with chronic HCV but had no association with degree of hepatic inflammation. As little as 100 mg or more of caffeine daily may be beneficial in a general HCV-infected population with a high prevalence of other risk factors for advanced liver disease. However, study authors noted that an average of 100 mg or more of caffeine daily from sodas and teas does not have the same protective effect as 100 mg or more of caffeine daily from combined sources (coffee, tea, soda) or from coffee alone, suggesting that caffeine alone may not entirely explain the effect of coffee on liver disease.

The authors conclude the following: “we found that an average daily intake of 100 mg or more of caffeine was associated with a lower risk of hepatic fibrosis in a general clinical population with chronic HCV infection. We further showed that in non–coffee drinkers, daily caffeinated tea intake also may protect against progressive liver disease in this population. Our study further suggests that caffeinated coffee overall and caffeinated tea in non–coffee drinkers likely provide the most benefit in liver disease compared with other caffeinated beverages or decaffeinated coffee. Future prospective studies are warranted to determine the optimal dose and preparation of caffeinated beverage intake that could be safely and tolerably recommended for prevention of progressive liver disease in HCV patients in routine clinical practice.”


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