T. Yakovleva, O. Demin Jr, O. Demin; Institute for Systems Biology Moscow, Moscow, Russian Federation
BACKGROUND: The hepatitis C progression starts with acute phase after infection with hepatitis C virus (HCV). The infection resolves spontaneously in about 20%. In the rest part of patients the chronic hepatitis C is developed. The aim of work WAs to reproduce the dynamics of hepatitis C progression and to describe the treatment with PEG-Interferon (PEG-IFN) and ribavirin (RBV) in patients with different genotypes and IL-28b polymorphism.
METHODS: A system of ordinary differential equations describing healthy hepatocytes maturation, proliferation and apoptosis, HCV entry into hepatocytes, hepatocytes infection and recovery, apoptosis of infected hepatocytes, HCV synthesis and degradation, PK and PD of PEG-IFN and RBV was developed. Models parameters were taken or fitted using experimental data.
RESULTS: The model describes hepatocytes proliferation in healthy subjects after liver resection, level of infected hepatocytes in chronic hepatitis C patients, dynamics of serum HCV after infection and during RBV monotherapy and RBV/ PEG-IFN combination for patients with different genotypes and IL-28b polymorphism.
CONCLUSION: The systems pharmacology model of hepatitis C progression could be used as a tool for evaluation, comparison and prediction of different therapies outcomes in both acute and chronic hepatitis C patients.