Second hepatitis C replication compartment indicated by viral dynamics during liver transplantation

Background/Aims: The existence of an extrahepatic hepatitis C virus replication compartment is an important question for optimizing therapy and preventing the infection of liver grafts. An extraheptic replication compartment could be indicated if viral decline during the anhepatic phase is not a single exponential. However, the duration of the anhepatic phase is too short (0.5-2 h) to allow such analysis. Here we mathematically analyze viral decline during liver transplantation beyond the period of the anhepatic phase and examine the possibility of viral compartmentalization. Methods: Viral load of 30 patients undergoing liver transplantation was frequently measured. Simulation and non-linear fitting of differential equation models were used to test different compartmentalization hypotheses. Results: In 16 of the patients (56%), a bi-phasic viral decline was observed which is explained by the existence of a second replication compartment. This extrahepatic compartment is responsible for about 3.1% of virus in circulation and the mean half-life of its infected cells is 2.6 days. The remaining patients, with a single exponential decline, have either a second compartment with relatively low contribution or no second compartment. Conclusions: These results provide a first quantitative picture of the extrahepatic hepatitis C viral contribution and may suggest new approaches for viral clearance.