Activation and apoptosis of peripheral T cells in relation to liver fibrosis

Hepatic fibrosis or liver scarring is the final common pathway of chronic liver
disease in which apoptotic hepatocytes activate fibrogenous stellate cells.
Activated and apoptotic T cells are also involved in hepatic fibrogenesis,
although their precise contribution remains unclear. Preliminary results from a
phase 2b study of a caspase-inhibitor in chronic hepatitis C virus (HCV)
patients in which our medical centre participated shows increased activation
and apoptosis of both peripheral CD4+ and CD8+ T cells in HCV patients compared
to healthy controls. It is unclear whether these findings are specific for HCV.

The primary objective is to explore the association between peripheral T-cell
activation and apoptosis and hepatic fibrosis in various underlying liver
diseases. Secondary objectives are 1) to investigate whether level of T cell
activation and apoptosis correlates with severity of fibrosis; 2) whether
activation and apoptosis of T cells differ between chronic HCV monoinfected
patients and those coinfected with HIV for which they are adequately treated 3)
to evaluate whether T cell activation and apoptosis differs between
non-symptomatic HBV carriers, active HBV hepatitis patients and treated HBV
patients.

markers of T cell activation and apoptosis are measured in peripheral blood of
patients with various hepatic diseases (asymptomatic hepatitis B virus (HBV)
carriers, active but untreated HBV, treated HBV, HCV, HIV-HCV, non-alcoholic
fatty liver disease (NAFLD) and primary biliary cirrhosis (PBC)) and various
stages of fibrosis (F0-F2 versus F3-F4; except for NAFLD-cases).
T cell activation and apoptosis rates are compared between patients with
hepatic diseases (viral hepatitis, PBC, NAFLD) to healthy controls or, in the
case of HIV-HCV co-infecten, to HIV mono-infected patients. Subsequently, in
patients with viral hepatitis and PBC, T cell activation and apoptosis rates
will be compared between those subjects with mild fibrosis (F0-F2) versus
severe fibrosis (F3-F4).

50mL of blood will be obtained from subjects of our study, of which risks and
complications are negligible. Participation in this study will not provide
individual benefit, but group-related benefit will include a first
understanding of the level of T cell apoptosis and activation in patients with
liver fibrosis with various underlying liver diseases and potential improvement
of diagnostics and therapy in long term.