This review, based on nearly 30
000 HCC cases, confirms wide international variation in the relative importance of HBV and HCV in this disease. As expected, HBV infection was found substantially more often than HCV infection in HCC cases from the majority of Asian and African countries with the available data. Conversely, more HCC cases were found to be anti-HCV+
in Europe and in the United States, as was also the case in Japan, Pakistan and Mongolia, and in Asia generally. In some countries (i.e., China and Mongolia), more than 10% of HCC cases were coinfected with both hepatitis viruses, thus hampering the attribution of a fraction of HCC cases to HBV or HCV.
More than half of HCC cases were both HBsAg−
in the United States and some North European countries, thus pointing to the relative importance of heavy alcohol consumption and, possibly, smoking, obesity and diabetes mellitus (Yuan et al, 2004
) in areas where hepatitis virus prevalence and HCC incidence are low.
Our systematic review failed to identify information on HBV and HCV infection among HCC cases in Eastern Europe, Russia, Central Asia and the majority of African and Latin American countries. None of the studies we found from Oceania using second- or third-generation ELISA met our inclusion criteria. However, a record-linkage study from New South Wales, Australia showed a similar proportion of HBsAg+
(45%) and anti-HCV+
(53%) HCCs and low frequency of HBV/HCV coinfection (2%) among 281 virus-related HCC cases (Amin et al, 2006
In addition to lack of data from many parts of the world, some weaknesses of our present review should be borne in mind. The extent to which the HCC cases we reported upon are representative, at a national level, is unclear, especially where only small studies were available. Furthermore, important secular trends may be concealed by our analysis, as in the largest study identified (Lu et al, 2006
), which showed a steady increase in the proportion of HCC cases related to HCV in the last two decades in Taiwan. The vast majority of studies did not provide information on occult HBV infection. Occult HBV infection seems, however, to have little or no clinical significance, at least among immunocompetent individuals (Knoll et al, 2006
). Most importantly, owing to the long latent period of HCC, seropositivity among HCC cases does not reflect the current importance of the two viruses in the relevant population but rather that two or three decades earlier.
Based upon prevalence of the infections in different populations around the world and a relative risk of 20 for both viruses, Parkin (2006)
estimated the fraction of HCC attributable to HBV and HCV in 2002 to be, respectively, 23 and 20% in developed countries and 59 and 33% in developing countries. Our simpler approach, based on HCC cases only, was mainly dictated by the wish to use information from many world populations for whom information on HCC was available but not data on population prevalences of HBV and HCV. It suggests, however, that the relative contribution of HCV to the current HCC burden in middle-aged and old individuals in developed countries and in some developing countries might be higher than in Parkin (2006)
. In fact, seroprevalence surveys on which attributable risks are based tend to over-sample young individuals at low risk of HCV infection (e.g., blood donors and pregnant women, WHO, 1999
; Madhava et al, 2002
). In conclusion, our findings underline the importance of the prevention of HCV infection that, in the absence of a vaccine, will require an integrated strategy including screening of blood donations, safe injection practices and avoidance of unnecessary injections (Ahmad, 2004