What determines the natural history of recurrent hepatitis C after liver transplantation?

Abstract

Hepatitis C virus (HCV) cirrhosis is the most common indication for liver transplantation in developed countries. Re-infection of liver allografts is virtually universal and occurs at reperfusion [1,2]. A significant increase in viral load is typically observed following transplantation, presumably as a consequence of the administration of immunosuppressive agents for the prevention and treatment of rejection. In this setting, HCV mediated liver injury follows a more aggressive course compared to the non-immunosuppressed state, leading to recurrent disease and allograft failure in a substantial proportion of patients [1–3]. While it seems evident that the immune suppressed status ‘per se’ modifies the natural history of hepatitis C in liver transplant recipients, the effect of several other factors on determining both the pattern and severity of recurrence still remains a matter of intense research. Identifying the factors, whether present prior to transplantation or developing in the post-transplant setting, that impact on the natural history of recurrent hepatitis C is of paramount importance not only to target those at high risk of severe recurrence with current imperfect and difficultto-tolerate antiviral therapies but also to improve organ allocation and patient management. In this review, I will summarize the available data regarding risk factors associated with cholestatic hepatitis, severe chronic recurrent hepatitis and severe but delayed-onset hepatitis. I will also describe the determinants of higher mortality in this population, and those associated with clinical