Elsevier

Journal of Hepatology

Volume 60, Issue 3, March 2014, Pages 606-611
Journal of Hepatology

Research Article
Mediterranean diet and hepatocellular carcinoma

https://doi.org/10.1016/j.jhep.2013.10.034Get rights and content

Background & Aims

Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial.

Methods

We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding factors, including chronic infection with hepatitis B/C viruses.

Results

Compared to MDS of 0–3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41–1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34–0.75) for MDS ⩾5, with a significant trend (p <0.001). The detrimental effect of poor adherence to Mediterranean diet on HCC risk was disproportionally high among those chronically infected with hepatitis B and/or C viruses, with a suggestion of super-additive interaction, albeit statistically non-significant.

Conclusions

Closer adherence to the Mediterranean diet appears to be protective against HCC. Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses.

Introduction

Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. The predominant role of chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the aetiology of HCC is well documented [1]. Several other risk factors for HCC have been identified, including heavy alcohol intake, tobacco smoking, and obesity [2].

With the exception of aflatoxins, data on the role of diet on liver cancer are inconclusive. Some studies have shown a weak inverse association between fruit consumption and liver cancer risk, and a positive one with glycaemic load, but evidence is sparse and inconsistent [3], [4].

It has been reported that for certain diseases, notably coronary heart disease, no food, food group, or nutrient has been implicated as causal, but the evidence for a favorable role of the Mediterranean dietary pattern is convincing [5]. Data are much scantier on Mediterranean diet and cancer risk [6], [7], [8], [9]. Because HCC is a disease with a very poor prognosis, with a 5-year survival rate of less than 10% [10], any effort to identify additional modifiable causes of liver cancer would be important in order to allow a more effective prevention of the disease.

We have therefore evaluated the association between the Mediterranean dietary pattern and liver cancer by combining two large case-control studies undertaken in Italy and Greece, two countries in which the traditional Mediterranean diet is still prevalent. Age-standardized mortality from primary liver cancer (mainly HCC) is around 3/100,000 population in these countries [11]. Thus, despite being more common than in most other high income countries, HCC is still a rare disease, with a lifelong cumulative incidence around 1% in the general population.

Section snippets

Selection of cases and controls

The present data are derived from case-control studies of HCC in two Mediterranean countries.

The first study was conducted between 1999 and 2002, in the province of Pordenone (north-eastern Italy) and in the city of Naples (southern Italy) [12]. Cases were 258 patients under the age of 85 years with incident (newly diagnosed) HCC. Of the HCC cases, 29 cases did not provide a blood sample and 44 did not provide data on dietary habits, thus leaving 185 eligible cases for the present analysis. The

Results

Table 1 presents the main characteristics of cases and controls in the Italian and Greek studies, separately, for descriptive purposes. The prevalence of current smokers is higher in the Greek study than in the Italian one; 80% of cases and 11% of controls in the Italian study and 75% of cases and 4% of controls in the Greek study had serological evidence of chronic infection with HBV and/or HCV.

With regard to the main recognized HCC risk factors, after mutual adjustment, the ORs were 1.33 (95%

Discussion

Combining two large studies carried out in the Mediterranean region, we found that the degree of adherence to Mediterranean diet is significantly inversely related to HCC risk in a roughly monotonic way, so that the MDS ⩾5 was associated with an about 50% reduction in HCC incidence in comparison to MDS of 3 or less. We also found that there is evidence, albeit statistically non-significant, of super additivity in the risk implications of joint chronic hepatitis B and/or C infection and poor

Financial support

This work was supported by the contribution of the Italian Association for Cancer Research (Grant N. 10068), and the Kapodistrias program of the University of Athens, Greece. F.T. was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC), and F.B. by a fellowship of the Fondazione Umberto Veronesi.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Acknowledgments

The authors thank Ms. Garimoldi for editorial assistance.

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