Epidemiology of Liver Diseases in Yamanashi Prefecture in Japan

The descriptive epidemiology of liver diseases in Yamanashi prefecture is reviewed with special emphasis on time trends. Age-adjusted death rates for liver cancer in males is increasing, but other data of SMR are showing gradual decreases. In the endemic area of schistosomiasis, SMR of liver cancer and cirrhosis in males are both increasing. The relationship between schistosome and liver cancer is also reviewed. The indirect theory seems to be accepted rather than the direct theory. However, further studies are necessary.


INTRODUCTION
In Japan the geographical distribution of mortality rates for liver diseases (liver cancer and liver cirrhosis) is generally high in south-western areas.However, Yamanashi prefecture showed a particularly high mortality for liver diseases in the east of Japan.Yamanashi Prefecture has had a considerably large endemic area of schistosomiasis japonica for several hundreds years.The relationship between liver cancer and schistosomiasis was recently reviewed in several articles(1-3) from various viewpoints.In this paper I would like to review this subject with special emphasis on time trends and on all liver diseases including liver cancer.

Mortality of Liver Diseases in Yamanashi Prefecture
Table 1 shows the mortality rates of liver diseases in Japan and in Yamanashi prefecture from the latest (1989) vital statistics (4).It reveals that almost all mortality rates for liver diseases except viral hepatitis are higher in Yamanashi prefecture than in Japan as a whole.
The time trends of crude mortality for liver cancer and liver cirrhosis in Yamanashi prefecture compared with those in Japan are shown in Fig 1 and 2. The mortality of male liver cancer has been markedly higher in Yamanashi prefecture than in Japan.Trends of age-adjusted

Mortality of Liver Diseases in the Endemic Area of Schistosomiasis
In Yamanashi prefecture, there are 20 municipalities which had at least one reported case of schistosomiasis in 1960.The total population of these municipalities is about 400,000 and is almost the same as the total for the other 44 municipalities in the prefecture.
Fig. 3 and 4 show the trends of SMR for liver cancer and liver cirrhosis in the endemic area and the non-endemic area.It is clear that the male SMR for liver cancer and liver cirrhosis are increasing in the endemic area.In another study (6)   Trends of Schistosomiasis Fig. 5 shows the trends of schistosomiasis related indicators.No incidence cases have been reported since 1980, and also no positive cases have been found in fecal examinations since 1977.However, there have been a few death cases every year and about 20% of the autopsy cases have been found to be egg-positive of schistosome in recent years.Schistosomiasis is still a serious disease in this area.

Relationship between Schistosomiasis and Liver Disease
In the early days, some researchers thought schistosoma itself might directly cause various liver diseases including liver cancer.In 1913, J. Fibiger published his work on gastric cancer experimentally induced by parasite (spiroptera carcinoma), and he received the Nobel Prize for Physiology and Medicine in 1926 (7).In the same year Katada reported a geographical correlation between schistosomiasis and cancer of the liver or large intestine in Yamanashi prefecture (8).Although the direct causation theory has been denied for long time because of no confirmed experimental study, in 1988, Amano and Oshima published findings to the effect that hepatoma was experimentally formed in mice by cercaria of schistosomes (9).The mechanisms of cancer formation of schistosomes has become a very interesting theme again.However, in recent studies, it has been the main stream of thought that schistosome has an indirect role in causing liver cancer.Two papers experimentally confirmed a promotive effect of schistosome on liver cancer (10)(11), and some articles based on observing human beings suggested the combination effect of hepatitis B virus (HBV) and schistosome on liver cancer (12)(13)(14).Moreover, considering that hepatitis C virus (HCV) has been detected recently, frequent intravenous injections of therapeutic reasons to the patients of schistosomiasis before 1965, might have caused infection of not only HBV but also HCV, and these viruses may have caused the liver cancer and other liver diseases.In the future further studies are necessary to elucidate the pathogenesis of liver diseases.Yamanashi Prefecture may be a useful area to continue these studies.

Figure 1 Figure 2
Figure 1 Trends of mortality for liver cancer in Japan and Yamanashi prefecture

Figure 3 Figure 4
Figure 3Trends of SMR for liver cancer Figure 5 Trends of schistosomiasis related indicators

Table 1
Mortality for Liver Diseases in Japan and Yamanashi Prefecture(1989)