What the past holds for the present and future of chronic liver disease: a population-based longitudinal study of the impact of chronic viral hepatitis and autoimmune liver disease in a northern Italian region
Progetto Chronic liver diseases remain a major source of morbidity and mortality as well as expenses for national health systems worldwide [Kim et al., Hepatology 2002; Grant et al., Hepatology 2005]. Quite surprisingly, limited data are available on the prevalence of chronic viral and autoimmune liver diseases in the general Italian population, despite their relevance from a clinical and management standpoint. Most available studies are not based on representative populations or solid randomization while no longitudinal data have been reported. Liver cirrhosis cumulatively affects 1% of the Italian population (adding up to 3% of the cumulative causes for death in the Country) [Pendino et al., Hepatology 2005] and, along with primary liver cancer, remains a significant cause for mobility and mortality worldwide. Of note, up to 40% of adults with liver cirrhosis are not aware of their disease. Beside alcohol abuse, chronic infections by hepatitis B (HBV) and C (HCV) viruses and autoimmunity (particularly primary biliary cirrhosis, PBC) [Selmi et al., J Hepatol 2008] constitute the major causes for liver cirrhosis adding up to over 75% of cases worldwide [Williams, Hepatology 2006].
The present project is based on a unique resource of subjects identified as affected by HBV or HCV or carrying the PBC serum hallmark (antimitochondrial antibody, AMA) within a study performed in 1999. This study was designed to determine the prevalence and risk factors for HBV and HCV infections but data were not reported in the scientific literature. For all subjects demographic and contact information as well as basic liver function tests (including AST, ALT, GGT) were collected and are currently available to the proponent. Among participants 145 were positive for anti-HCV antibodies and 154 for HBV surface antigen (HBsAg), while we most recently determined that AMA were detected in 0.77% of tested sera. No longitudinal study has been undertaken thus not allowing to evaluate the presence of chronic infections and viral load was determined only in a subgroup of cases.
The aims of the present study go well beyond previous data by taking advantage of the long follow-up and more modern laboratory techniques and will address three major issues.
Issue #1. What was the prevalence of active viral and autoimmune liver diseases in the general population in 1997?
Issue #2. What was the long-term outcome of subjects that had signs of active viral infection or liver autoimmunity 12 years before?
Issue #3. Are there overlooked major determinants of the disease natural history in chronic viral hepatitis or primary biliary cirrhosis?
These aims have obvious implications in the management of healthcare while the resources already available to the proponent at a significant lower cost compared to a de novo population-based study account for a unique opportunity to investigate the true impact of chronic liver diseases in such areas.