In this study, we compared prospectively the life expectancy and final outcomes of all hepatitis C patients detected by screening with sex- and age-matched HCV antibody-negative general residents in a specific area. The median follow-up period exceeded 10 years, the follow-up survey was excellent in that only 10% of cases had unknown final outcomes.
As mentioned above, because the subjects were residents of an isolated island, where immigration and emigration were relatively rare, the follow-up was quite successful. Moreover, environmental factors, such as medical care, were comparable between the two groups as a result of approximating birth date in the same residential district when choosing general residents who matched the subjects in the hepatitis C group. Furthermore, the accuracy of the comparative study in cases with and without persistent HCV infection was considered to be excellent.
Hepatocarcinogenesis can be prevented in hepatitis C when HCV is persistently undetectable and transaminases are normalized by IFN treatment [6
]. In addition, it is reported that IFN treatment improves the life prognosis in hepatitis C [17
]. However, no report has prospectively examined the effect of IFN treatment with HCV antibody-negative general residents as controls; to our knowledge, the present study is the first of its kind.
In terms of the overall prognosis of hepatitis C, the survival rate was lower than in the HCV antibody-negative general residents; the hazard ratio was 0.444 (95% CI: 0.389–0.507). Liver disease-related death accounted for 42.8% of all causes of death in the hepatitis C group; this greatly exceeded the 1.5% for the general residents. The survival rate in the patients persistently infected with HCV was markedly low and their prognosis was extremely poor.
We then determined to what extent IFN treatment improved the prognosis of the hepatitis C group. The patients younger than 70 years who had indications for IFN treatment and had no LC or HCC were compared to the general resident group. When SVR was obtained by IFN treatment, the prognosis in the hepatitis C group was comparable to that in the general resident group. Kaplan–Meier analysis showed almost overlapping curves for the two groups. In cases with non-SVR, despite the slightly lower survival rates in the general resident group, the prognosis in the hepatitis C group was not significantly different. Taken together, irrespective of the effect of IFN treatment, the survival rate of members of the hepatitis C group who received IFN treatment was comparable to that of the general resident group.
Yoshida et al. [18
] reported that the standardized mortality rate from all causes was 1.4 (0.8–2.3) in a non- LC group without IFN treatment compared to 0.3 (0.1–0.7) in an SVR group after IFN treatment and 0.7 (0.5–1.1) in a non-SVR group after IFN treatment; these results are consistent with ours. It may be reasonable to conclude that to a certain extent, intervention with IFN treatment eliminates the risk of hepatocarcinogenesis due to persistent long-term infection with HCV. Furthermore, achieving SVR eliminates the risk almost completely. Even in cases with non-SVR, the risk of hepatocarcinogenesis was reduced and the prognosis became closer to that of the general resident group.
Regarding the results obtained using death from all causes as the endpoint, we presumed the following: First, the group receiving IFN treatment had a higher awareness of health management and continued periodical medical check-ups and clinic visits with a greater frequency than the group without IFN treatment. Second, we presumed that this higher awareness of health management had a preventive effect against a variety of diseases in addition to liver disease and enabled effective treatment following early disease detection.
In this study, IFN treatment introduction was not assigned randomly; therefore, there was a difference in the backgrounds between the two groups. There was a bias in that the IFN–treated group had a higher proportion of males and more cases with ALT values exceeding the normal range. In general, male sex and high transaminase levels are risk factors for hepatocarcinogenesis; the survival rate in such cases is low [2
]. However, even in such cases with a high risk for hepatocarcinogenesis, introduction of IFN treatment reduced the mortality from HCC and improved the survival rate; furthermore, the prognosis was comparable to that in the general resident group.
Yoshida et al. reported that IFN treatment improved the prognosis of hepatitis C in a retrospective cohort study [18
]. Although their conclusion is consistent with ours, our study is a prospective cohort study, and the median of the follow-up period exceeded 10 years. Moreover, our study is unique in that it is a comparative study with HCV antibody-negative general residents of the same district in the same time period as controls.
Nagao et al. carried out a survey of patients infected with HCV in a district of Japan and reported that the factors that influence the acceptance of IFN treatment are the clinics the patients visited, sex, and the presence or absence of concomitant disease [28
]. Because patients infected with HCV have been getting older in Japan, cooperation between liver specialists and non-experts in individual districts is important to introduce IFN treatment as early as possible, particularly for people under 70 years.