Long-term morbidity and mortality risk in Japanese insurance applicants with chronic hepatitis C virus infection.

BACKGROUND

Japan has the highest rate of liver cancer of any industrialized country in the world, and research indicates that hepatitis C virus (HCV) is responsible for 50-76% of these cases. The natural history of chronic HCV infection is difficult to determine because the initial bout of acute infection is usually not recognized and serious complications generally do not develop for at least 3 decades. This article discusses use of a Markov model to estimate long-term morbidity and mortality risk associated with chronic HCV infection in otherwise healthy Japanese insurance applicants. A range of risk estimates is derived based on different assumptions of disease progression.

RESULTS

Data for this analysis were based on prospective and combined retrospective-prospective studies of populations infected at different ages and followed for durations of up to 25 years. Estimated mortality ratios varied with assumptions regarding rate of progression from active HCV infection to cirrhosis. For males, peak mortality ratios decreased with advancing age at underwriting, from a high of 253% (age 20) to a low of 144% (age 60). A similar age-related pattern was seen for females, from a peak mortality ratio of 222% (age 20) to a low of 156% (age 60). In contrast to the pattern of decreasing relative mortality at older ages, morbidity increased with age at underwriting. Sensitivity analysis indicated that calculations in the model were sensitive to different transition rates from active HCV infection to cirrhosis and from cirrhosis to HCC, but were not sensitive to treatment frequency and success or the percentage of people treated prior to application. A review of the literature also suggested that a favorable prognosis was likely in applicants with persistently normal ALT levels, but prognosis was less certain for those with intermittent or persistent elevation of liver enzymes.

CONCLUSION

Morbidity and mortality are within the insurable range for the majority of HCV-infected persons. Risk varies with gender, age at infection, and other variables discussed in the article.