Abstract and Introduction
Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted.
Coffee is a brewed beverage with a distinct aroma and flavor, prepared from the roasted seeds of the coffee plant. It has been part of the human diet since the 15th century. In its various forms (including decaffeinated coffee), coffee is one of the most consumed drinks in the world, partly for its mild mood-enhancing and stimulatory effects on the central nervous system. Caffeine, one of the main constituents of coffee, has been shown to have a wide spectrum of biological activities. The effects of coffee on chronic liver disease, especially in lowering the risk of developing hepatocellular carcinoma (HCC) has recently attracted considerable attention.
During the last 20 years, several investigators have focused on the potential beneficial health effects of coffee, especially against liver disease. In 1992, Klatsky and Armstrong reported an inverse relationship between coffee drinking and the risk of cirrhosis in a 10-year follow-up study of a large number of subjects using multivariate analysis by Cox proportional hazards model. Coffee drinking also decreased the risk of clinically significant chronic liver disease. Other studies show that coffee drinkers (at least 3 cups/day) had significantly lower levels of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), serum alkaline phosphatase, and bilirubin concentration compared with non-coffee-drinking subjects or those consuming less than three cups daily. Coffee consumption has also been associated with decreased blood GGT levels in humans, and reported to confer possible hepatoprotection against alcoholic liver disease.[4,5]
On the other hand, authors found caffeine intake did not appear to affect liver stiffness (detected by transient elastography) in patients with chronic hepatitis B virus (HBV). A preliminary conclusion from these observations is that if coffee has a protective effect against cirrhosis in HBV infection, this is not as significant as the viral determinants of chronic liver disease.
More than 180 million people worldwide are chronically infected with the hepatitis C virus (HCV), and approximately 350 000 people die every year from HCV-related liver disease, such as decompensated cirrhosis and/or HCC. Some case–control studies have shown that coffee consumption is associated with reduced risk of HCC among HCV-infected patients.[7,8] Costentin et al. found that caffeine consumption of > 408 mg/day (≥ 3 cups coffee) was associated with reduced histological activity in patients with chronic HCV infection. However, there was no relationship between coffee consumption and fibrosis severity. Finally, coffee consumption may improve virological response to pegylated-interferon and ribavirin antiviral treatment.[10,11]
Coffee consumption may be associated with a reduced risk of HCC.[12–16] This relationship appears to be very consistent, and the effect is a powerful one. Thus, four meta-analyses found that inverse relationship between coffee and HCC risk.[17–20] Further, the relationship between coffee intake and decreased risk of HCC has been observed for several etiological types of chronic liver disease. In those with chronic HBV infection, moderate coffee consumption (drinking coffee ≥ 4 times/week) was associated with a reduced risk of HCC by half (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.30–0.97) with a significant dose–response effect (χ2 = 5.41, df = 1, P = 0.02). In another hospital-based case–control study, it was found that a high lifetime coffee consumption (≥ 20 000 cups) was an independent protective factor against HCC in all subjects. However, high levels of coffee consumption did not significantly affect HCC risk in patients with HBV (OR = 0.64, 95% CI: 0.36–1.14) after adjustment for HBeAg status, serum HBV DNA level, and antiviral therapy.
The prevalence of non-alcoholic fatty liver disease (NAFLD) is escalating rapidly worldwide in association with such metabolic disorders as type 2 diabetes mellitus (T2DM), obesity, hypertension, and hyperlipidemia (metabolic syndrome). NAFLD comprises a pathological spectrum characterized by fat accumulation within the liver known as simple steatosis, or "non-NASH NAFLD," and/or in combination with varying degrees of hepatocellular injury manifested by ballooning, inflammation, liver fibrosis, cirrhosis, and HCC. In NAFLD-related cirrhosis, liver histology may no longer show inflammation or even steatosis, and this likely represents the largest proportion of cases often referred to as "cryptogenic cirrhosis." The diagnosis of NAFLD is usually made by abnormal liver tests and hepatic imaging showing features of fatty infiltration ("bright liver") in the context of obesity, a family history of diabetes, and/or features of metabolic syndrome; as well, other causes of liver disease and significant alcohol intake must be excluded.
Several studies of hepatic lipid metabolism, insulin resistance, mitochondrial dysfunction, oxidative stress, as well as genetic predisposition to altered cell metabolism and injury have contributed to current understanding of NAFLD. Lifestyle measures directed at increasing physical activity (which counters insulin resistance) and weight loss remain the cornerstone of management. Notably, the effects of pharmacotherapy are still contentious; most agents studied are either modest in their effects, such as vitamin E, pioglitazone, ezetimibe, or pentoxifyllne, or have no beneficial long-term hepatoprotective effects (e.g. metformin, ursodeoxycholic acid). In general, moderate energy and simple carbohydrate restriction, reduction of total and saturated fat intake, along with increasing physical activity are beneficial and highly recommended. Interestingly, recent studies have shown that coffee drinking may be protective against NAFLD-related chronic liver disease and possibly, HCC.
J Gastroenterol Hepatol. 2014;29(3):435-441. © 2014 Blackwell Publishing