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To The Editor:

With great interest we read the recent article in HEPATOLOGY by Rohr-Udilova et al.,1 who showed that reduced selenium (Se) levels and the subsequent reduced oxidative capacity lead to the accumulation of lipid peroxides producing reactive oxygen species (ROS) in patients with hepatocellular carcinoma (HCC). They set out to determine the effect of low Se levels on vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) expression, both of which are crucial in the development and growth of HCC. Interestingly, they found that Se levels correlated inversely with VEGF and IL-8 levels and also with tumor size in small HCC nodules. This finding is in agreement with previous studies showing that patients with chronic viral hepatitis and HCC had significantly lower Se plasma levels compared to those without HCC.2, 3

To further address this important association, we prospectively studied 32 age-matched male Caucasian patients with chronic hepatitis C virus (HCV) infection: 12/32 patients had no evidence of liver cirrhosis (HCV-CH), 10 patients had liver cirrhosis (HCV-LC), and 10 patients had liver cirrhosis and HCC (HCV-HCC). In addition, 10 healthy age-matched male individuals were followed as a control group. Several exclusion criteria were defined: antiviral therapy or HCC-specific treatment during the last 6 months, use of dietary supplements, local or systemic inflammation, extrahepatic tumors, and diabetes mellitus. Females were excluded to avoid a gender-dependent influence on Se levels. Se levels were determined in whole blood samples using graphite furnace atomic absorption spectroscopy.

Interestingly, Se levels were significantly different between patients with HCV-CH compared to patients with HCV-LC (99.8 ± 11.0 μg/L versus 84.7 ± 16.4 μg/L; P = 0.021) and compared to patients with HCV-HCC (99.8 ± 11.0 μg/L versus 85.0 ± 11.5 μg/L; P = 0.009). In patients with liver cirrhosis with and without HCC, however, Se levels did not differ significantly (84.7 ± 16.4 μg/L versus 85.0 ± 11.5 μ/L; P = 0.99; Fig. 1). Healthy individuals had significantly higher Se levels (117.5 ± 15.7 μg/L) in comparison to all patient cohorts (HCV-CH [P = 0.006], HCV-LC [P = 0.001], HCV-HCC [P = 0.001]).

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Figure 1. Comparison of Se levels. Patients with chronic hepatitis had higher mean Se levels than patients with liver cirrhosis and HCC. Healthy individuals had significantly higher Se levels than patients with chronic hepatitis, liver cirrhosis, and HCC (P = 0.006, P = 0.001 and P = 0.001, respectively).

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In conclusion, our findings of reduced Se levels in patients with liver cirrhosis and/or HCC extend the results by Rohr-Udilova et al. and support the hypothesis that low Se levels may play an important role in the early steps of hepatocarcinogenesis. These results provide the rationale for further epidemiological studies focusing on the preventive role of Se supplementation in patients with chronic liver diseases.

References

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  • 1
    Rohr-Udilova N, Sieghart W, Eferl R, Stoiber D, Bjorkhem-Bergman L, Eriksson LC, et al. Antagonistic effects of selenium and lipid peroxides on growth control in early hepatocellular carcinoma. HEPATOLOGY 2012; 55: 1112-1121.
  • 2
    Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J Epidemiol 1999; 150: 367-374.
  • 3
    Lin CC, Huang JF, Tsai LY, Huang YL. Selenium, iron, copper, and zinc levels and copper-to-zinc ratios in serum of patients at different stages of viral hepatic diseases. Biol Trace Elem Res 2006; 109: 15-24.

Dominik Bettinger*, Michael Schultheiβ M.D.*, Nadine Hennecke*, Elisabeth Panther M.D.*, Eva Knüppel*, Hubert E. Blum M.D.*, Robert Thimme M.D.*, Hans Christian Spangenberg M.D.*, * University Hospital Freiburg, Department of Medicine II, Freiburg, Germany.