Coffee consumption and liver function

In 2016, the International Agency for Research on Cancer (IARC) published an updated review of the scientific evidence related to coffee and cancer, finding no conclusive evidence for a carcinogenic effect of coffee overall, and, concluding that the research suggests an inverse association between coffee consumption and liver cancer¹.

Four meta-analyses of both prospective cohort and case control studies, looking at liver cancer, concluded that all ten of the reviewed epidemiological studies showed an inverse association between coffee consumption and liver cancer^2-5. The results of the cohort studies included in the meta-analyses indicated a dose-response relationship between frequency of coffee consumption and a reduced risk for liver cancer.

The results from the US Multi Ethnic Cohort study also suggest that coffee consumption is inversely related to the incidence of hepatocellular cancer, showing a risk reduction of 38% in those who drank 2-3 cups of coffee per day and 41% in those who drank more than 4 cups³⁶. Two large studies have also shown a similar association^37,38, with a risk reduction of up to 72% in the highest coffee drinkers in the EPIC study³⁷, and of 54% in women who drank more than 3 cups of coffee a day in the US Consortium³⁸. Interestingly, the US study showed a greater effect in women compared to men³⁸. Data from Finland has considered the role played by the type of coffee, concluding that coffee intake was inversely associated with incident liver cancer and mortality from chronic liver disease, irrespective of whether the coffee was boiled or filtered³⁹.

The inverse association between coffee consumption and liver cancer is observed both in participants with and without a history of liver disease. For example, studies in patients with hepatitis have suggested that coffee consumption is associated with a reduced risk of hepatocellular carcinoma^40-42, with one of the studies highlighting the potential role for lifetime coffee consumption⁴¹. A further study has suggested that coffee consumption over 3 cups a day is associated with a decreased risk of liver cancer recurrence and provides for increased survival following liver transplantation⁴³.

Overall, drinking coffee has been associated with up to a 40% reduced risk of liver cancer compared to those who do not drink coffee^36-42.

Coffee and risk of other liver diseases

Coffee drinking has also been related to a reduced risk of other liver diseases. A systematic review published in 2014 suggested coffee consumption was associated with beneficial outcomes in patients with chronic liver disease, cirrhosis, hepatocellular cancer and NAFLD⁶. A 2016 review also concluded that coffee intake of more than 2 cups per day in patients with pre-existing liver disease was associated with a lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, and decreased mortality⁸.

Liver fibrosis

• A review concluded that patients with higher coffee consumption display a milder course of fibrosis¹¹.
• Data from the US National Health and Nutrition Examination Surveys (NHANES 1999-2010) suggests that higher intakes of coffee (including decaffeinated coffee) were associated with beneficially lower levels of liver enzymes⁴⁴.
• Data from the Rotterdam Study Research also suggested that daily coffee consumption of three or more cups decreases liver stiffness (a marker of liver fibrosis)⁴⁵.
• A cross-sectional study assessing the impact of a variety of food groups suggested that tea and coffee consumption had a protective role in hepatic fibrosis independent of other risk factors⁴⁶.

Chronic liver disease

• A Scottish study suggested that coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease⁹.
• Data from the US Multi Ethnic Cohort concluded that coffee drinking was associated with a reduced incidence of chronic liver disease. Compared to non-coffee drinkers, consuming 2-3 cups per day was associated with a 46% reduction in risk of death from chronic liver disease, and greater than 4 cups a day with a 71% reduction³⁶.

Non-alcoholic fatty liver disease

• NAFLD is a common liver disease and a major cause of cirrhosis and hepatocellular carcinoma. It is defined by presence of steatosis in 5% of hepatocytes or more in the absence of other causes of fatty liver. The metabolic syndrome is a major known risk factor for NAFLD⁴⁷.
• A North American study investigated the effects of dietary behaviour in NAFLD patients, using four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES 2001-2008). It found caffeine intake to be independently associated with a lower risk of NAFLD, suggesting a potential protective effect¹³.
• A 2012 study correlated coffee caffeine consumption with the prevalence and severity of NAFLD. Coffee caffeine consumption was associated with a significant reduction in risk of fibrosis among patients with non-alcoholic steatohepatitis¹⁴.
• A Mexican case-control study looked at the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with NAFLD, and in patients without NAFLD. They found that a high intake of coffee had a protective effect against non-alcoholic fatty liver disease; however there was no significant difference in the antioxidant variables analyzed¹⁵.
• Data from 728 adults in the Non-alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) suggests that coffee intake was inversely associated with advanced fibrosis in patients with non-alcoholic fatty liver disease¹⁶.
• Five further reviews found a significantly decreased risk of liver fibrosis among patients with NAFLD who drank coffee^17-19. One of these reviews further suggested that regular coffee caffeine consumption, not total caffeine intake, was associated with a reduced risk¹⁸.
• A further systematic review and dose response analysis concluded that coffee intake of more than 3 cups per day was associated with lower risk of NAFLD than less than 2 cups per day, and suggested that the relationship was non linear²⁰.

Hepatitis C

• A prospective cohort US study recruited 766 hepatitis C-infected patients and followed them up for nearly four years²². A total of 229 patients showed serious disease progression, e.g. cirrhosis or 2-point increase in Ishak fibrosis score (a histological grading of progression to fibrosis, with scores ranging from 0 to 6). Tea consumption was not associated with the study outcomes. However, regular coffee consumption was statistically significantly associated with lower rates of disease progression.
• A French study developed to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with chronic hepatitis C found that caffeine consumption over 408 mg/day was associated with reduced histological activity in these patients²³.
• A study of patients with the Hepatitis C virus suggested that amongst those with a chronic infection, daily consumption of filtered coffee may have a beneficial effect on the stabilisation of the liver enzyme serum alanine aminotransferase (ALT)²⁴.
• Data from the Singapore Chinese Health Study, a population-based cohort of 63,275 adults, suggested that there was a strong dose-dependent inverse association between coffee intake and risk of non-viral hepatitis related cirrhosis. Compared to non-coffee drinkers, those who drank more than 2 cups per day had a 66% reduction in mortality risk. However, there was no association between coffee intake and hepatitis B related cirrhosis mortality⁷.

If patients change their habits or diet as a result of their disease or its standard therapy, this can bias the observational study. Therefore it is important to assess whether such confounders are adequately taken into account. Case control-studies are particularly susceptible to bias, in particular when other patients are used as controls; prospective cohort studies are less susceptible to this type of bias.

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