1. Volume 42, Issue 4, Pages 491-498 (April 2005)
Second hepatitis C replication compartment indicated by viral dynamics during liver transplantation 
Harel Dahari, Anna Feliu, Montserrat Garcia-Retortillo, Xavier Forns, Avidan U. Neumann 
Journal of Hepatology 
Volume 42, Issue 4, Pages (April 2005)
DOI: /j.jhep
Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

2. Fig. 1
Three possible biological hypotheses for viral compartmentalization. Schematic models of HCV dynamics with (A) one compartment (OC) model, where it is assumed that viral replication occurs only in the liver; (B) second replication compartment (SRC) model, where an extrahepatic replication compartment exists in addition to the liver; (C) binding compartment (BC) model, where a virus is attached to a second compartment and released with a slow off-rate into the circulation. TL and IL, represent non-infected and infected hepatocytes, respectively. T2 and I2, represent non-infected and infected cells of the second compartment. VL and V2, represent virions released into circulation from infected hepatocytes and from infected second compartment cells. Vb, represents the bound virions; whereas, kon and koff represent the virions binding and dissociation constant rates.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

3. Fig. 2
Representative viral decline patterns and fitting results. A and B patients with only a rapid viral decrease. C and D patients with a rapid decrease and a viral plateau. E and F patients with rapid and slow viral decreases. Solid line is the best fit of the models to the viral load data (circles). A and B were fitted by the OC model; while C, D, E and F were fitted by the SRC/BC models. The observed viral plateau during the long anhepatic phase in patient 2F, which continues also after graft reperfusion, can only be explained by the second compartment models. Full black circles indicate viral load below detection (<100IU/ml). Fitted parameter values and viral kinetics patterns are given in Table 1.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

4. Fig. 3
Simulation results of the three models during liver transplantation. In principle, each of the three viral kinetics patterns observed during LT can be fitted by all three models. (A) A straightforward simulation of the OC model predicts a single exponential viral decline both during the anhepatic phase and after graft reperfusion followed by a viral increase at time tp, when the new de novo infectious graft cells release virions into the circulation. Thin line represents de novo infected cells of the liver graft. Where sL=1.0e5, dL=0.01, tp=7.2, δL=0.03, c=8.4, βL=1.2e−6 and pL=2.1. (B) The OC model can show a bi-phasic viral decline after graft reperfusion, if at the time tp only a limited replication starts (pL=0.6 and tp=2.2), and is later (4 days after reperfusion) accelerated (pL=2.5) to onset a viral rebound. However, there is no evidence for the aforementioned assumption and fitting the data to the model requires an unlikely short time tp of less than 2–3h. Where sL=1532, dL=0.001, c=5.9, δL=0.7 and βL=2.8e−6. (D) and (F) Simulation of the SRC and BC models predicts a single exponential viral decline both during the anhepatic phase and after reperfusion, followed by a slower viral decline that represents the viral contribution from the second compartment. Triangles represent a liver-produced virus from the extracted liver. Dashed lines represent the viral contribution from the second replication compartment (D) or a disassociated virus from the binding compartment (F). Where sL=1.0e6, dL=0.01, δL=0.08, c=5.9, βL=3.6e−6, pL=0.06, tp=105, s2=1.0e2, d2=0.01, δ2=0.41, β2=1.8e−6, and p2=25 (D) and sL=1.0e5, dL=0.001, δL=0.001, c=6.3, βL=1.3e−8, pL=3, tp=110, kon=0.35 and koff=0.57 (F). (C) and (E) SRC and BC models can also give rise to a single exponential decline immediately followed by a viral increase at time tp, assuming that these patients have a short productive anhepatic phase or a very low extrahepatic viral contribution. Where sL=1.0e6, dL=0.02, δL=0.08, c=10, βL=2.0e−8, pL=138,tp=14, s2=1.0e2, d2=0.5, δ2=0.64, β2=6.2e−6, and p2=25 (C) and sL=1.0e5, dL=0.001, δL=0.001, c=10, βL=2.0e−8, pL=20, tp=16, kon=0.42 and koff=1.0 (E). Experimental viral load for each patient is indicated by circles. Solid lines represent the total viral load in circulation. Parameters units are: sL,2=[cells/day/ml], βL,2=[ml/day/virion], c=dL,2=δL,2=κon,off=[1/day], pL,2=[virion/day/cell] and tp=[hours].
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2005 European Association for the Study of the Liver Terms and Conditions