Commentary: Modelling the epidemiology of hepatitis C and its complications

Hepatitis C virus (HCV) was well adapted to emerge worldwide in the late 20th century. Transmitted primarily through percutaneous routes, it took advantage of two emerging epidemics: an epidemic of recreational injection drug use in industrialized countries and an epidemic of unsafe injections primarily in developing countries, made possible by the expanded use of parenteral therapeutics and declining injection equipment prices after the World War II. The result at the beginning of the 21st century is a large pool of HCV-infected people, many of whom have asymptomatic, slowly progressing liver disease. The greatest burden from HCV infection will come from the long-term complications of this chronic liver disease, namely cirrhosis and hepatocellular carcinoma, which in any individual may take decades to develop. Whether increases in HCV infections in the 20th century will lead to increases in HCV-related complications in the 21st will depend on three factors: the number of people currently infected with the virus, the stage of disease in these individuals, and the natural history of HCV infection. These determinants are often difficult to measure directly and have not been well characterized. Only the first, the size of the infected population, has been estimated on a global scale. One recent review of published and unpublished literature puts this number at 130 million worldwide, though the precision of this estimate is limited by the paucity of data from representative, population-based surveys of HCV infection and from important regions such as the Indian subcontinent (CDC, unpublished data). The other two determinants of future burden are even less certain. Data from natural history studies suggest that progression to cirrhosis is much slower in people infected as children or young adults, of whom fewer than 5% have progressed to cirrhosis in the first 20 years, than in people infected as older adults, of whom 10‐20% have progressed to cirrhosis in the first 20 years. 1 Beyond 20 years there are few data on what to expect and no data to suggest whether disease progression will accelerate or decelerate. In addition, co-morbidities such as alcohol use and human immunodeficiency virus infection may substantially alter the natural history of chronic hepatitis C. Where currently infected individuals are along this natural history is even less well understood and depends in part on how long these 130 million individuals have been infected, a function of past trends in incidence of HCV infection. With few direct data about these trends, mathematical modelling provides an appealing means of inferring them. Several countries have used modelling to examine trends in hepatitis C and its complications. Australia, in the accompanying paper by Matthew Law and colleagues, has approached this task by assuming that injection drug use has driven the epidemiology there and that infections from other sources have been proportional to infections from injection drug use. 2 They first estimated past trends in injection drug use and then, assuming a certain incidence of infection among drug users, estimated the number of HCV infections by year. To project the current and future burden of HCV-related cirrhosis and liver cancer, they applied to these estimates a natural history model that assumes the rate of progression to cirrhosis will be 5.3% at 20 years and 15.3% at 40 years. Their model fits existing data well and shows a monotonic increase in HCV infections over the past 30 years, portending a monotonic increase in HCVrelated complications in the near future. Groups working in other industrialized countries have used different approaches to infer past trends in incidence and to project the burden of disease. In the US, the Centers for Disease Control and Prevention (CDC) has estimated the past incidence by first assuming that acute hepatitis C cases identified by sentinel