1. Hepatitis C virus in the human liver transplantation model
Hugo R. Rosen, MD 
Clinics in Liver Disease 
Volume 7, Issue 1, Pages (February 2003)
DOI: /S (02)

2. Fig. 1
Allograft biopsy findings at 1 and 5 years in HCV–positive liver transplant recipients, with findings at 5 years in HCV-negative patients. The majority of HCV-infected patients demonstrate histologic recurrence by year 1, and 20% have allograft cirrhosis by year 5. (From Gane EJ, Portmann BC, Naoumouv NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Eng J Med 1996;334:821–7; with permission.)
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

3. Fig. 2
Hepatitis C virus kinetics during and after liver transplantation. Two representative patients demonstrating the most common pattern: rapid increase in viral load, reaching pretransplantation levels by day 4. (From Garcia-Retortillo M, Forns X, Feliu An, Moitinho E, Costa J, Navasa M, et al. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology 2002;35(3):680–7; with permission.)
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

4. Fig. 3
Neighbor joining phylogenetic trees constructed from NS3 gene sequences (nt ) of all study patients (severe [S1-S16] and mild [M1-16] recurrence). Distinct clusters of viral sequences corresponding to each individual patient were found, but there were no differences between patients with mild versus severe histologic recurrence. (From Rosen HR, Marousek G, Chou S. A longitudinal analysis of T cell epitope coding regions of hepatitis C virus after liver transplantation. Transplantation 2002;74:209–16; with permission.)
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

5. Fig. 4
Levels of HCV RNA as measured by Taqman PRC (log-transformed values) and the fibrosis score at the time of the 5-year routine biopsy after liver transplantation. The error bars indicate standard deviations. (From Giguo M, Roque-Afonso AM, Falissard B, Penin F, Dussaix E, Feray C. Genetic clustering of hepatitis C virus strains and severity of recurrent hapatitis after liver transplantation. J Virol 2001:75:11292–7; with permission.)
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

6. Fig. 5
Flow cytometric analysis of intrahepatic lymphocytes from (A) Patient with HCV-related liver failure. (B) Patient with amyloidosis (and histologically normal liver explant). Note the relative percentages of lymphocytes expressing T cell and NK markers and the decrease of NK and NKT cells in the HCV-infected patient.
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

7. Fig. 6
Immune reconstitution of HCV-specific T cell immunity in a recipient treated pre-emtively with interferon α-2b ribavirin starting 2 weeks after liver transplantation and continued for 48 weeks. Using the IFN-γ ELISPOT assay with whole recombinant proteins, there is emergence of new CD4+ T cell responses at 2 months that inversely correlates with viral load (patient became HCV RNA negative in serum by 4 months post-LT). CD8+ T cell frequencies were determined by soluble HLA A2-HCV peptide tetramers (immunodominant core 131–140 and N –1081 peptides) after magnetic bead separation of purified CD8+ T cells. HCV viral load was assessed by b-DNA Quaniplex 3.0 (Bayer).
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

8. Fig. 7
Intrahepatic and peripheral CD4+ T lymphocytes were expanded nonspecifically (for 10 days) from peripheral blood and from a 4 mm liver biopsy (6 months after liver transplantation) with anti-CD3:anti-CD4 (CD3,8) bispecific mAb that causes selective cytolysis of CD8+ lymphocytes (by bridging the CD8 molecules to the CD3 complex with concurrent activation and proliferation of residual CD3+CD4+ T cells). Phenotyping revealed significant differences in cell surface expression between both compartments, with enrichment for activated memory cells within the allograft.
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

9. Fig. 8
Intrahepatic CD4+ T lymphocytes in (A) patient with mild typical allograft hepatitis caused by recurrent HCV (total Knodell histologic activity index, 5) and in (B) severe cholestatic HCV. Note the marked difference in Th1/Th2 polarization, with IL-4 production predominating in the latter patient. CD4+ T lymphocytes have been expanded as described in Fig. 7.
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

10. Fig. 9
(Top) Potential contributing factors in HCV recurrence. (Bottom) conceptual paradigm for HCV-specific T cell responses in shaping viral replication and allograft injury post-LT. Patients responding to antiviral therapy demonstrate viral clearance concurrent with early emergence of CD4+ and CD8+ T cells. Patients who demonstrate mild histologic recurrence despite high viral loads demonstrate lack HCV-specifc T cells as assessed by ELISPOT and tetramer analyses.
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )

11. Fig. 9
(Top) Potential contributing factors in HCV recurrence. (Bottom) conceptual paradigm for HCV-specific T cell responses in shaping viral replication and allograft injury post-LT. Patients responding to antiviral therapy demonstrate viral clearance concurrent with early emergence of CD4+ and CD8+ T cells. Patients who demonstrate mild histologic recurrence despite high viral loads demonstrate lack HCV-specifc T cells as assessed by ELISPOT and tetramer analyses.
Clinics in Liver Disease 2003 7, DOI: ( /S (02) )