Blackadar raises the question whether high intake of marine products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may partly explain the low incidence rate of hepatocellular carcinoma (HCC) found among HBsAg-positive individuals in our population-based cohort study in Greenland.
Although EPA and DHA appear to have protective effects against cardiovascular disease ( 1 ), firm evidence of protective effects against cancer is lacking ( 2 ). Conflicting results have been published on the association between n-3-fatty acids and HBV/HCC. However, recently Sawada et al. concluded that consumption of n-3 fatty acids (in particular, EPA, docosapentaenoic acid [DPA], and DHA) appears to protect against development of HCC, also among subjects with HBV ( 3 ), through the anti-inflammatory effects on chronic hepatitis.
Traditional Greenlandic food is rich in EPA and DHA. It can, therefore, seem reasonable to assume that EPA and DHA may contribute to the low incidence of HCC among HBsAg-positive individuals in Greenland.
However, the mechanism of liver damage in chronic HBV infection needs to be considered. In HBV infection, the liver injury is caused by the host’s immune attack against HBV, mediated by a cellular immune response. The hepatic flares are due to the resurgence of host immunity against HBV-infected hepatocytes. The extent of chronic liver disease is related to the duration, severity, and frequency of hepatic flares and results in fibrosis, which in time may lead to cirrhosis and HCC ( 4 ). Severe hepatitis is sometimes observed on withdrawal of immunosuppression, presumably the result of an enhanced immune response. The immunotolerant phase in chronic infection, observed in individuals infected perinatally, is characterized by a high viral load, HBeAg posititivity and normal ALT level, as the host immune system is tolerant to HBV.
Eight genotypes of hepatitis B virus, A–H, and a number of sub-genotypes exist. The predominant HBV sub-genotype in Greenland is B 6 . This sub-genotype appears to have coexisted with the Greenlandic population for at least 1000 years and is related to the B 1 sub-genotype found in Japan, which is associated with less severe disease ( 5 ). Adaptation over time of both the virus and the host’s immune response to cohabitation may lead to improved survival for both the virus and the host ( 6 ).
It may be speculated that the absence of cirrhosis and HCC among chronic HBsAg-positive individuals in Greenland may be attributable to a balanced coexistence of HBV and the Greenlandic host developed over centuries. In contrast, an effect of n3-fatty acids would reinforce the host immune response towards trying to eliminate HBV, which could result in flares. We, therefore, do not believe that n-3 fatty acids explain the low incidence rate of cirrhosis and HCC in the Greenlandic population. Further studies on the interaction between host and HBV virus in Greenland are warranted to elucidate if particular host genetic factors or host-viral interactions are present in Greenland.