Metabolic Syndrome Is Also a Risk Factor for Primary Liver Cancer in Patients Younger than 65 Years of Age?


  • Potential conflict of interest: Nothing to report.

To the Editor:

We read with great interest the article by Welzel et al.1 The study reported a positive association between metabolic syndrome and hepatocellular carcinoma (HCC), but the results were restricted to people aged ≥65 years of age. Although the incidence of obesity and/or metabolic syndrome is showing no sign of decline, the epidemic of hepatitis B (HBV) and C (HCV) viruses is at its peak, thus increasing the incidence of HCC.2, 3 To provide further insights on the association of HCC and metabolic syndrome on the interaction with HBV/HCV infection, we report data from an Italian case–control study on HCC. The study was conducted between 1999 and 2002 in the province of Pordenone, Northeastern Italy, and in Naples, Southern Italy.4 Cases comprised 185 patients aged 43-84 years (50% below age 65 years) with incident HCC, who had not yet received any cancer treatment at study entry. The control group included 412 cancer-free patients from the same areas as the cases.4

Metabolic syndrome was associated with a four-fold higher risk of HCC. The association was confirmed among hepatitis B surface antigen (HBsAg)-negative and antibody to HCV (anti-HCV)-negative subjects (odds ratio [OR] = 4.00; 95% confidence interval [CI] = 1.30-12.27). According to the individual preexisting medical condition, only diabetes was significantly associated with HCC risk (OR = 3.75; 95% CI = 1.66-8.44; Table 1). This result was in agreement with a recent study.5

Table 1. Multiple Logistic Regression Analysis Examining the Association Between HCC and Each Preexisting Medical Condition Contributing to Metabolic Syndrome
Preexisting Medical ConditionsN%N%OR (95% CI)*P Value
  • *

    Adjusted for center, sex, age, education, drinking status, maximum lifetime alcohol intake, smoking status, cigarettes per day, hepatitis B surface antigen (HBsAg) and/or antibody to HCV (anti-HCV) positivity, when appropriate.

All study subjects185 404   
 Diabetes3720.0266.43.75 (1.66-8.44)0.0001
 Hypercholesterolemia21.1245.90.52 (0.08-3.39)0.63
 Hypertension4122.211628.71.17 (0.63-2.17)0.50
 Obesity11461.625863.91.26 (0.72-2.20)0.42
 Metabolic syndrome105.4164.04.00 (1.30-12.27)0.015
HBsAg-negative and anti-HCV-negative38 360   
 Diabetes923.7236.43.52 (1.34-9.23)0.011
 Hypercholesterolemia12.6236.40.69 (0.08-5.81)0.73
 Hypertension1642.110128.12.07 (0.92-4.65)0.078
 Obesity2976.323264.41.95 (0.82-4.67)0.13
 Metabolic syndrome615.8154.24.19 (1.23-14.23)0.022

Our results are therefore in agreement with the study by Welzel et al.1; in particular, our study confirms that metabolic syndrome is also a risk factor for HCC in people younger than 65 years (50% of our study population).

Our results on metabolic syndrome, together with heavy drinking (in the North) and high HCV prevalence (in the South), contribute to explain the high incidence of and mortality rates from HCC in Italy.3, 6 In order to reduce the burden of liver cancer, actions to control the recent epidemic of metabolic syndrome should be promoted.


The authors gratefully acknowledge The Italian League Against Cancer (LILT), Project n. 11/2008.

Maurizio Montella M.D.*, Jerry Polesel Sc.D.†, Renato Talamini M.D.†, Anna Crispo Sc.D.*, Aldo Giudice Sc.D.*, Francesco Izzo M.D.‡, Carlo La Vecchia Ph.D.§ ¶, * Unità di Epidemiologia, stituto Nazionale dei Tumori Fondazione “G. Pascale” Naples, Italy, † Dipartimento di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico—IRCCS, Aviano, Italy, ‡ Divisione di Chirurgia “D”, Istituto Nazionale dei Tumori Fondazione “G. Pascale,” Naples, Italy, § Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy, ¶ Istituto di Statistica Medica e Biometria “G. A. Maccacaro,” Università degli Studi di Milano, Milan, Italy.