摘要
Background/Aims: The existence of an extrahepatic hepatitis C virus replicatio n compartment is an important question for optimizing therapy and preventing the infection of liver grafts.An extraheptic replication compartment could be indic ated if viral decline during the anhepatic phase is not a single exponential.How ever, 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 transplantat ion beyond the period of the anhepatic phase and examine the possibility of vira l compartmentalization. Methods: Viral load of 30 patients undergoing liver tran splantation was frequently measured. Simulation and non-linear fitting of diffe rential equation models were used to test different compartmentalization hypothe ses.Results: In 16 of the patients (56%), a bi-phasic viral decline was observ ed 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 patient s, with a single exponential decline, have either a second compartment with rela tively low contribution or no second compartment. Conclusions: These results pro vide a first quantitative picture of the extrahepatic hepatitis C viral contribu tion and may suggest new approaches for viral clearance.
Background/Aims: The existence of an extrahepatic hepatitis C virus replicatio n compartment is an important question for optimizing therapy and preventing the infection of liver grafts.An extraheptic replication compartment could be indic ated if viral decline during the anhepatic phase is not a single exponential.How ever, 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 transplantat ion beyond the period of the anhepatic phase and examine the possibility of vira l compartmentalization. Methods: Viral load of 30 patients undergoing liver tran splantation was frequently measured. Simulation and non-linear fitting of diffe rential equation models were used to test different compartmentalization hypothe ses.Results: In 16 of the patients (56%), a bi-phasic viral decline was observ ed 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 patient s, with a single exponential decline, have either a second compartment with rela tively low contribution or no second compartment. Conclusions: These results pro vide a first quantitative picture of the extrahepatic hepatitis C viral contribu tion and may suggest new approaches for viral clearance.
