Dynamics of Liver Disease in Egypt: Shifting Paradigms of a Complex Etiology.

Abstract

The burden of liver disease in Egypt is exceptionally high, maintaining the highest prevalence of hepatitis C virus (HCV) worldwide, as well as rising rates of hepatocellular carcinoma (HCC). The foundation of the HCV epidemic in Egypt is generally attributed to a mass public health campaign to eliminate schistosomiasis during the 1960’s-1980’s. Questions remain regarding the precise incidence of HCV during this campaign, the future burden of chronic disease those affected will experience, and the future direction of HCV and liver disease now that this campaign has ended. This dissertation offers a series of studies designed to precisely define the nature of HCV infections and HCC in Egypt, spatially and temporally, as well as predict the future burden and impact on the Egyptian population. Specific methods included analyses of HCC case data collected from the Gharbiah Population-based Cancer Registry (GPCR) to define demographic and spatial trends in the occurrence of HCC in Egypt, in addition to a meta-analysis and the construction of two mathematical models designed to calculate historic incidence of HCV and project future HCV-related health complications. Results identified significant heterogeneity in HCC occurrence with respect to sex and district of residence. More in-depth investigation identified significant spatial clustering of HCC associated with clusters of squamous cell carcinoma of the bladder (a proxy measure for schistosomiasis burden). Meta-analysis revealed the HCV epidemic is marked by a three-way interaction between time, geographic region, and whether individuals reside in urban or rural environments. Modeling techniques confirmed the presence of a cohort effect among those affected by the public health campaign, identified by a spike in incidence among those presently aged 30-50 years. The natural history model predicted Egypt will experience significant morbidity and mortality over the next 20 years due to the HCV epidemic. Our findings highlight the significance of developing an integrated strategy for the prevention of HCV infection. Unquestionably, additional factors contributing to liver disease burden remain to be elucidated. This information is crucial and should help define the complex etiology of liver disease in Egypt, enabling policy makers to create targeted, more efficient prevention and control programs.Ph.D.Epidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60651/1/lehmane_1.pd