Poster 734

Abstract ID: 66682

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Patient Survival and Fibrosis Progression After Liver Retransplantation for Hepatitis Coinfection.

M. Ghabril, Mayo Clinic Jacksonville, Jacksonville, FL, M. Krishna, Mayo Clinic Jacksonville, Jacksonville, FL, A. Keaveny, Mayo Clinic Jacksonville, Jacksonville, FL, J. Aranda-Michel, Mayo Clinic Jacksonville, Jacksonville, FL, B. Rosser, Mayo Clinic Jacksonville, Jacksonville, FL, D. Harnois, Mayo Clinic Jacksonville, Jacksonville, FL, R. Satyanarayana, Mayo Clinic Jacksonville, Jacksonville, FL, H. Grewal, mAYO cLINIC jACKSONVILLE, Jacksonville, FL, D. Willingham, Mayo Clinic Jacksonville, Jacksonville, FL, W. Hewitt, Mayo Clinic Jacksonville, Jacksonville, FL, J. Nguyen, Mayo Clinic Jacksonville, Jacksonville, FL, C. Hughes, Mayo Clinic Jacksonville, Jacksonville, FL, J. Steers, Mayo Clinic Jacksonville, Jacksonville, FL, R. C. Dickson, Mayo Clinic Jacksonville, Jacksonville, FL

 

Background

Hepatitis C infection (HCV) is the leading cause of liver transplantation  (LT). However, retransplantation (RLT) for HCV is controversial due to variable reported outcomes. Aim: To review outcomes & histologic

progression in pts undergoing RLT for graft failure secondary to recurrent HCV.

Methods

A retrospective review of all RLT in pts with previous LT for complications of HCV at a single center between 2/1998-4/2004.Pts undergoing RLT for recurrence of HCV & non-HCV pts with LT-RLT interval (RI)>90 days (d)

were included. Pt & donor characteristics, bilirubin (Bili), creatinine (Cr) &

hospitalization status at RLT were collected. MELD & Childs Pugh score (CPS) at RLT were calculated. A single blinded pathologist scored HCV pts liver biopsies (Ishak score) at 4 months (mth) & 1 year (yr) post LT & RLT. Results

124 RLT were performed in the study period, including 27 for recurrent HCV (grp1) & 23 RLT for non-HCV pts (grp2) who met the study criteria. The overall 1yr survival was 74% & 78% respectively. Causes of death in grp 1 were recurrent HCV(1), biliary stricture(1),cardiac(2),sepsis(2),& HUS/TTP(1). 3 pts per grp received a third graft with 2 per grp surviving at follow up (grp1 grafts failed<30 d, unrelated to HCV). The differences between groups are shown in the table below. 1yr mortality in grps 1 & 2 was associated with pts age>60*(67 & 75%), hospitalized pts (40 & 50%,grp2*) & intensive care at RLT(50 & 33%,grp1*).1yr

mortality was increased in grp1 pts with RI<1yr *(50%) & donor age>60*(100%). Despite a trend towards increased mortality with Bili>10(33 & 33%), Cr>2(40 & 25%), MELD>25(36 & 40%) & CPS>9(35 & 50%,grp2*), grp1 pts exceeding these parameters at RLT had a 60 to 67% 1yr survival with a mean follow up 988 d(373-1874).  Grp1 mean grade & stage were similar at 4mth post LT & RLT(4.8 & 1.5 vs 3.6 &

1.1) but decreased at 1yr post RLT**(5.9 & 2.4 vs 2.8 & 0.7).1yr fibrosis

progression was decreased post RLT**(-0.8 vs 2.4 points/yr).

 

Conclusion

Short term survival & histologic progression after RLT for HCV recurrence were acceptable in a single center experience in the last 5 yrs.  Mortality was increased with pt & donor age>60,hospitalization & intensive care

at RLT, & RI of less than 1 year. Mortality was not related to HCV recurrence. Further study is required to better define prospective RLT criteria in this pt population.

 


Poster 735

Abstract ID: 67476

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Non invasive assessment of liver graft fibrosis by transient elastography after liver transplantation.

C. Barrault, Department of Hepatology Hôpital Henri Mondor, Créteil, France, F. Medkour, Department of Hepatology Hôpital Henri Mondor, Créteil, France, C. Atanasiu, Department of Hepatology Hôpital Henri Mondor, Créteil, France, C. Douvin, Department of Hepatology Hôpital Henri Mondor, Créteil, France, F. Roudot-Thoraval, Department of Public Health Hôpital Henri Mondor, Créteil, France, A. Mallat,,Department of Hepatology Hôpital Henri Mondor, Créteil, France, S. Zafrani, Department of Pathology Hôpital Henri Mondor, Créteil, France, C. Duvoux, Department of Hepatology Hôpital Henri Mondor, Créteil, France, J. Tran Van Nhieu, Department of Pathology Hôpital Henri Mondor, Créteil, France

 

BACKGROUND AND AIMS

Transient elastography (TE) (FibroScan, Echosens, Paris, France), is a validated method of quantification of liver fibrosis in HCV patients. It may be useful in the follow-up of liver transplant (LT) recipients, especially in patients with HCV recurrence, because of accelerated course of the disease. The aim of this study was to assess the diagnosis accuracy of TE in evaluating liver fibrosis after LT, in patients with or without recurrent HCV.

 

METHODS

Thirty patients underwent liver biopsy and TE concomitantly after LT. Liver fibrosis scoring was assessed on biopsy specimens by 2 pathologists according to Metavir (F0 to F4), to Ishak (from 0 to 6) scores, and to a modified Ishak score taking into account septa thickness and centrilobular perisinusoidal fibrosis (from 0 to 10). Efficiency of transient elastography and optimal stiffness cut-off values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis.

 

RESULTS

The study population consisted of 83% males and 17% females. LT indications were HCV cirrhosis in 22 (73.4%), alcoholic cirrhosis in 5 (16.6%) and miscellaneous in 2 (6.6%). Mean age at elastography was 55.9±9.2 months. Elastography and liver biopsies were performed 57.1±43.3 months after LT. Elastography discriminated well between patients with significant and non significant fibrosis [median stiffness value in Ishak scores 0 to 2, vs 3 to 6 : 5.1 (IQR: 4.3-8.3) vs 9.6 (IQR: 7.4-12.1), p=0.007]. Discrimination was better with Ishak score than with METAVIR score. The areas under ROC curves were 0.80 for Ishak scores > or = 3 (95 % CI, 0.64-0.96) and 0.77 for modified Ishak score > or = 4 (95 % CI, 0.59-0.94). Optimal stiffness cut-off value was 7 kPa for Ishak > or = 3 and modified Ishak > or = 4.

 

CONCLUSIONS

Transient elastography seems to be efficient to identify LT recipients with significant graft fibrosis. It is a promising tool to assess graft fibrosis progression after LT.


Poster 736

Abstract ID: 62520

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Recurrent Hepatitis C Virus Infection after Liver Transplantation and Concurrent Biliary Tract Complications: Poor Outcome.

L. H. Katz, Liver Institute and Department of Medicine D, Rabin Medical Center, Pe,Givat-Shemuel, Israel, E. Mor, Rabin Medical Center, Petah Tiqwa, Israel, Petah Tiqwa, Israel, N. Bar-Nathan, Rabin Medical Center, Petah Tiqwa, Petah Tiqwa, Israel, E. Shaharabani, Rabin Medical Center, Petah Tiqwa, Petah Tiqwa, Israel, J. Sulkes, Rabin medical center, Petah Tiqwa, Israel, O. Pappo, Rabin Medical Center, Petah Tiqwa, Petah Tiqwa , Israel, R. Tur-Kaspa, Rabin Medical Center, Petah Tiqwa and Sackler School of Medicine,, Petach Tiqwa, Israel, Z. Ben-Ari, Rabin Medical Center, Petah Tiqwa, Petah Tiqwa, Israel

 

Introduction

Recurrent HCV infection is particularly aggressive in the post-liver-transplantation setting, with rapid progression of liver fibrosis. Variables associated with fibrosis progression are under investigation. Biliary complications remain a significant cause of morbidity following liver transplantation, despite improved survival. Postcholecystectomy biliary strictures are associated with advanced hepatic fibrosis.

 

Aim

The aim of this retrospective study was to determine whether the presence of biliary complications affects survival in liver transplant recipients with recurrent HCV infection.

 

Method

The study group included 56 liver transplant patients (53.6% male; mean age 52.7 + 10.3 years). The incidence, types and treatment of biliary complications were documented in those who developed recurrent HCV infection (n=47) and those who did not (n=9). Outcome was compared between these two groups and between patients who developed severe recurrence (n=18) or non-severe recurrence (n=29). The effect of antiviral treatment (peginterferon and ribavirin; n=25) on outcome was assessed as well.

 

Results

Twentyone biliary complications developed in 12 transplant recipients with recurrent HCV (25.5%) {anastomotic strictures, n=8; nonanastomotic strictures, n=2; diffuse biliary strictures, n=3; sludge and stones, n=6; and biliary leak, n=2). Treatment consisted of endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography balloon dilatation and stent placement or surgical revision and was successful in 9 patients (75%). In addition, 3 biliary complications developed in the group with no recurrence (p=NS). There was no statistically significant association between recurrent HCV infection and biliary complications (p=NS). However, among those with recurrent disease, the recurrence was severe in 9 of the 12 recipients with biliary complications (75%) but in only 9 of the 37 recipients without biliary complications (26%); this difference was highly significant (p=0.0019). Eight patients with severe recurrence died (44.4%), including 3 (37.5%) with biliary complications, compared with 2 patients (7%) with non-severe recurrence, neither of whom had biliary complications (p=0.003). Antiviral treatment was successful in 9 of the 25 patients (36%) who received it. On multivariate analysis, biliary complications were a significant predictor of severe recurrence (OR 13.8, CI 2.4-77.9).

 

Conclusion

Biliary complications of liver transplantation strongly affect outcome in patients with recurrent HCV infection despite attempts to relieve the biliary obstruction and to treat the recurrent HCV infection.


Poster 637

Abstract ID: 63369

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Viral quasispecies and severity of recurrent hepatitis C.

A. Shakil, University of Pittsburgh School of Medicine, Pittsburgh, PA, L. Wang, University of Pittsburgh School of Medicine, Pittsburgh, PA, R. Shankarappa, University of Pittsburgh School of Medicine, Pittsburgh, PA, A. J. Demetris, University of Pittsburgh School of Medicine, Pittsburgh, PA, C. H. Chang , University of Pittsburgh, Pittsburgh, PA, J. J. Fung, Cleveland Clinic Foundation, Cleveland, OH, A. Marcos, University of Pittsburgh School of Medicine, Pittsburgh, PA

 

Introduction

Factors that influence the severity of recurrent hepatitis C in the liver allograft are not well understood. We initiated prospective follow-up of patients transplanted for HCV cirrhosis, to determine factors that influence the severity of recurrenthepatitis C.

 

Methods

Demographic, clinical, radiologic, virologic and pathologic features were studied. We also determined HCV E2 genomic diversity pre-transplant and at 3 months post-transplant by heteroduplex mobility assay using a defined number of viral templates. Our primary endpoint was severity of fibrosis at one year, with disease categorized as mild (fibrosis stage 0-2) or severe (fibrosis stage 3-6). Among 230 patients enrolled for prospective follow up, 50 recipients were included in the current analysis. Eight patients who died from severe disease before their one year biopsy were assigned a fibrosis stage of 6. Univariable and multivariable analyses were performed.

 

Results

The mean age of the recipients and donors was 52 years and 45 years, respectively. Patients with severe disease were likely to have received older grafts. Seventy percent of recipients were men and 96% were white. Fifty percent had donor recipient gender mismatch and 10% had race mismatch. The meanpre-transplant MELD was 13 with no difference among the two groups. There was no difference in pre-transplant serum bilirubin, creatinine, INR, HCV RNA levels and genotype distribution (84% genotype 1) between the groups. The cold and warm ischemia time and blood product usage was also similar. Induction T cell depletion (44%) and cumulative tacrolimus and steroid dosage were similar in the two groups. Thirty-six percent received interferon therapy during the study period with similar proportions in the two groups. Pre-transplant and 3 month post-transplant HCV viral diversity was significantly higher among patients with mild disease compared to those with severe disease. However, viral genomic complexity (entropy) was similar. On logistic regression analysis, pre-transplant HCV diversity and donor age were associated with severity of disease posttransplant (ROC AUC: 0.76).

 

Conclusions

Among transplant recipients with HCV, donor age and pretransplant HCV diversity are associated with the severity of recurrent disease at one year post-transplant. Further studies are needed to determine the utility of pre-transplant HCV diversity as a prognostic tool in transplant decision making.


Poster 738

Abstract ID: 64223

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Predictive factors of early and sustained viral response in patients with recurrent hepatitis C after liver transplantation treated with combined therapy (IFN-alpha and ribavirin).

T. Casanovas-Taltavull, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat, Spain, M. Llobet, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de LLobregat, Spain, A. Casanova, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat, Spain, J. Niubó, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat, Spain, T. Serrano, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat, Spain, C. Baliellas, Hospital Universitari de Bellvitge, Liver Transplant Unit, Hospitalet de Llobregat, Spain, N. Chahri, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain, B. Verdura, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain, R. Ballester, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain, E. de Lama, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain, C. Cañas, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain, J. Fabregat, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain The aim of the study is to investigate hepatitis C viral response in the liver transplantation

 

Introduction

(LT) population to help selection of appropriate candidates for treatment and/or therapies in the future.

Method

A prospective, observational study is currently ongoing, with the inclusion of all LT patients with histological diagnosis of recurrent hepatitis C, at any stage of fibrosis, who start combined therapy with IFN-alpha and ribavirin at our center.  Scheduled doses are: standard (STD) IFN-alpha-2a (3 MU thrice weekly) or pegylated (PEG) IFN-alpha (180 ìg weekly) plus ribavirin 600-1200 mg/day during 12 months (except for patients with histological cholestatic features and/or early severe recurrence, who receive 50-75% of antiviral doses). During antiviral therapy patients only receive

one immunosuppressive agent (anticalcineurin inhibitor). 52 patients (64% men, 55±10 years –mean±SD-, 92% genotype 1) have been included in the study of early virological response (EVR) (HCV-RNA negativity at 12 weeks after therapy initiation), with data on sustained virological response (SVR) (24 weeks after treatment) for 36 of them. Mean post-LT time is 4.5±3 years, and indication for LT was: 55% chronic liver disease, 39%

hepatocellular carcinoma, and 5% retransplantation. 48% received PEG-IFN and 52% STD-IFN, 44% of patients presented cholestatic features in the liver biopsy and/or early severe recurrence.

Results

There were 25% (13/52) of treatment discontinuations.  EVR was achieved in 36.5% of patients, and SVR in 47.2%, in an intention-to-treat analysis.

Significant predictive factors of EVR were: PEG-IFN (52% EVR vs. 22% for STD-IFN, p=0.02), high receptor weight (p=0.02), low donor BMI (p=0.02), non infiltration of polymorphonuclear leukocytes at post-reperfusion biopsy (p=0.02) and non histological cholestatic features (48% EVR vs. 22% for cholestatic hepatitis and/or early severe recurrence, p=0.04). Significant predictive factors of SVR were: EVR (p=0.01) and detection of autoantibodies detection during treatment (p=0.02). Subgroup of patients treated with cyclosporine (86%) displayed higher EVR (42%) and SVR (51%) rates than global sample, but a randomized controlled study would be necessary to investigate this finding.

Conclusion

A good viral response may be achieved with combined therapy for hepatitis

C recurrence in immunosuppressed patients, specially with PEG-IFN. It is important to evaluate EVR in order to predict SVR.


Poster 739

Abstract ID: 65959

Category: KO1: Clinical Transplantation: Viral Hepatitis C

MULTICENTER RANDOMIZED TRIAL OF HCV TREATMENT WITH PEGINTERFERON-ALFA 2A AND RIBAVIRIN AFTER LIVER TRANSPLANTATION:ONE-YEAR REPORT.

Y. Calmus, Service de Chirurgie, Hopital Cochin, APHP, Paris, France, C. Duvoux, Hopital Henri Mondor, Créteil, France, D. Samuel, Hopital Paul Brousse, Villejuif, France, G. P. Pageaux, Hopital Saint-Eloi, Montpellier, France, M. Messner, Hopital Pontchaillou, Rennes, France, P. Wolf, Hopital Hautepierre, Strasbourg, France, L. Rostaing, Hopital Rangueil, Toulouse, France, C. Vanlemmens, Hopital Minjoz, Besancon, France, Y. LeTreut, Hopital Conception, Marseille, France, S. Dharancy, Hopital Huriez, Lille, France, J. Guguenheim, Hopital de l'Archet, Nice, France, F. Durand, Hopital Beaujon, Clichy, France, M. Neau-Cransac, Hopital Pellegrin, Bordeaux, France, O. Boillot, Hopital Edouard Herriot, Lyon, France, L. Samelson, Laboratoires Roche, Neuilly, France, K. Boudjema, Hopital Pontchaillou, Rennes, France

 

Aim

The aim of this randomized, double blind study was to determine whether maintenance  therapy for one year with ribavirin (RBV) alone after a year of bitherapy with peginterferon-alfa 2a (PEG2A) and RBV, enhanced the eradication of HCV after liver transplantation (LT). Primary endpoints were the virological response at 12 (end of bitherapy) and 30 months (6 months after one year of maintenance therapy with RBV or placebo).

 

Results

We report here the results of the first year of treatment. Methods: 97 patients were included, with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring) on a liver biopsy obtained 1 to 5 years after LT. 75% of patients received tacrolimus and 25% cyclosporine. PEG2A was initiated at 90 ug/wk and RBV at 600 mg/d, then increased to 180 ug/wk and 1000 mg/d or adjusted as a function of hematological tolerance. Growth factor use was permitted. Therapy was stopped for intolerable side effects or cytopenia (hemoglobin < 8g/dl, PMN < 750/ul, platelets <30,000/ul). Results: At 52 weeks, HCV-PCR was negative in 62 % of patients(60/97), and in 75 % (58/77)of those who had completed 52 weeks of therapy (21% of patients did not complete the 52-week course of therapy). Viral response was 100 % in patients with genotype 2 or 3 and 65 % in patients with genotype 1 or 4 (p = 0.004). There was no correlation between viral response and histological score, biological parameters at inclusion or the type of calcineurin inhibitor. ALT transaminases were 133 ± 120 IU/l (SD) before therapy, and 52 ± 38 IU/l after one year (p = 0.001). Histological activity was 1.68 ± 0.77 before, and 1.11 ± 0.767 after therapy (p = 0.0001), whereas fibrosis remained unchanged (1.47 ± 0.71 and 1.61 ± 0.99, respectively, p = 0.06). 37% of patients required erythropoietin (EPO) support and 12% also required G-CSF. Globally, hemoglobin levels decreased from 13.7 ± 1.5 to 11.3 ± 1.5 g/dl. Serious antiviral-related adverse effects were observed in 15 patients: acute rejection was observed in 2, severe cytopenia requiring the discontinuation of antiviral therapy in 7, acute renal failure in 2, ischemic cardiopathy in 2, psychiatric disorders in 2, diabetes in 2.

 

Conclusions

Using PEG2A and RBV associated with a liberal use of EPO, a viral response was achieved in 74% of patients, with a low rate of side effects, including 2% of acute rejection and 2% of renal failure.


Poster 742

Abstract ID: 67071

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Long term results after therapy with pegylated interferon alpha 2a in HCV positive liver transplant recipients

M. Bahra, Charité - Campus Virchow, Dep. of Surgery, Berlin, Germany, U. P. Neumann, Charité - Campus Virchow, Dep. of Surgery, Berlin, Germany, D. Jacob, Charité - Campus Virchow, Dep. of Surgery, 13353 Berlin, Germany, J. M. Langrehr, Charité - Campus Virchow, Dep. of Surgery, Berlin, Germany, R. Neuhaus, Charité, Campus - Virchow, Dept. of Surgery, Berlin, Germany, P. Neuhaus, Charité – Campus Virchow, Dept. of Surgery, Berlin, Germany

 

Background

Hepatitis C reinfection after orthotopic liver transplantation (OLT) is a

major cause of graft loss in HCV positive liver graft recipients. We evaluated the efficacy and safety of pegylated interferon alfa-2a and ribavirin treatment for recurrent HCV after OLT.

Methods

60 patients with recurrent HCV received peginterferon alpha 2a (0.5 -

1.5&#61549;g/kg per week) and ribavirin (400-800mg/ day) for a minimum of 48 weeks. Including criteria were: positive test for anti-HCV and HCV RNA by RT-PCR, >2-3 times elevated serum alanine aminotransferase (ALT) levels before initiation of treatment, and a liver biopsy showing recurrent hepatitis C. Endpoint of the study was  defined by undetectable serum HCV-RNA 6 months after end of treatment (sustained

virologic response). Furthermore protocol biopsies were accomplished to evaluate the influence of pegylated interferon on fibrosis progression. Mean follow-up was 96 weeks.

Results

28/60 patients became HCV-RNA-negative after 48 weeks of treatment (46,6%).  Sustained virologic response (SVR) was achieved in 20/60 (33,3%) patients. Liver specimen showed increase of fibrosis from 0.8 to 1.25 (Metavir-Score). Side effects like neutropenia (51,6%) and anemia (38.3%) were treated with G-CSF, erythropoietine, and dose reduction of peginterferon and ribavirin. 12/20 patients with SVR received supportive treatment with growth hormones (4/20 G-CSF alone, 2/20 erythropoietine

alone and 6/30 G-CSF and erythropoietine). In five patients complete cessation of the pegylated interferon/ribavirin treatment was indispensable (8.3%).

 

Conclusion

The use of peginterferon alpha 2a is safe and effective in patients with

hepatitis C reinfection after OLT. The yearly fibrosis progression rate during interferon therapy tended to be decelerated. Treatment of neutropenia and anemia helped to maintain antiviral therapy and seemed to play a role to increase SVR rates.


Poster 743

Abstract ID: 67221

Category: KO1: Clinical Transplantation: Viral Hepatitis C

Antiviral therapy for HCV-1b liver transplant recipients: better results with younger grafts.

S. Benlloch, La Fe Hospital, Valencia, Spain, M. Berenguer, La Fe Hospital, Valencia, Spain, A. Fernández, La Fe Hospital, Valencia, Spain, A. Palau, La Fe Hospital, Valencia, Spain, V. Aguilera, La Fe Hospital, Valencia, Spain, M. Prieto, La Fe Hospital, Valencia, Spain, J. Berenguer, La Fe Hospital, Valencia, Spain

 

Introduction

With the introduction of pegylated interferon and ribavirin, improvements have been made in the treatment of post-transplantation chronic hepatitis C. Results though are worse than those obtained in non-transplant patients. Aims: to analyse whether the outcome of anti-HCV therapy is influenced by the age of the graft.

 

Methods

Analysis of efficacy (rate of end-of-treatment and sustained biochemical and virological responses) and tolerance (rate of treatment discontinuation, interferon and/or ribavirin reduction, use of growth factors) following antiviral therapy in a cohort of 66 HCV-1b infected recipients treated with standard (n=30) or pegylated (n=36) + ribavirin.

 

Results

An end-of-treatment (EOT VR) and sustained virological responses (SVR) were obtained in 45% and 30%, respectively. Of potential predictors of SVR analysed (gender, age, pretransplantation antiviral therapy, induction immunosuppression, history of significant alcohol, Child-Pugh and hepatocellular carcinoma at transplantation, rejection, rejection therapy, disease severity at initiation of therapy, laboratory tests – body mass index and viral load pre-antiviral therapy, type and duration of antiviral therapy, time from transplantation to therapy, interferon and/or ribavirin reductions, use of growth factors), both type of antiviral therapy (13% with standard IFN+Rbv vs 45% with pegylated IFN + Rbv; p=.02) and viral load at initiation of therapy (p=.05) were predictive of response. A trend was observed with regards to age of the donor with a median age of 37 years (17-69) in those achieving a SVR vs 48.5 (16-76) in non-responders (p=.056).

 

Conclusions

HCV clearance is achieved in a significantly higher proportion of HCV-1b infected liver transplant recipients treated with pegylated interferon-ribavirin compared to standard interferon-ribavirin. The age of the donor, variable known to influence disease progression, is also involved in the response to antiviral therapy.


Poster 744

Abstract ID: 67596

Category: KO1: Clinical Transplantation: Viral Hepatitis C

On treatment virological response of 70% in 100 patients treated with combination antiviral therapy for recurrent HCV following liver transplantation.

L. Lilly, University Health Network, Toronto, Canada, N. Girgrah, University Health Network, Toronto, Canada, A. Al Alwan, University Health Network, Toronto, Canada, B. McQuarrie, University Health Network, Toronto, Canada, P. Wong, University Health Network, Toronto, M. Cattral, University Health Network, Toronto, Canada, P. Greig, University Health Network, Toronto, Canada, I. McGilvray, University Health Network, Toronto, Canada, G. Levy, University Health Network, Toronto, Canada

 

BACKGROUND:

Chronic liver failure due to HCV infection is the leading indication for liver transplantation worldwide; disease recurrence after transplantation is inevitable. Short-term patient and graft survival following liver transplantation for hepatitis C are similar to other indications; long-term results are inferior. Response rates of recurrence to antiviral therapy are reported to be significantly lower than those seen in non-transplanted patients. A large single center experience is reported here.

 

PATIENTS & METHODS

100 patients (73% Genotype 1) with histologically-proven recurrent HCV received at least three months of combination therapy with Interferon/PEG-Interferon and Ribavirin between Jan 98 and Jan 05. Serum aminotransferases, HCV-RNA and histology were followed.

 

RESULTS

Seventy patients (70%) achieved an on-treatment virological response (OTVR) at a mean of 5m on treatment; 65 of these have become HCV-RNA negative. 12/30 non-responders remain on treatment (mean 13m); therapy was discontinued in 18/30, 4 for side effects and 14 for lack of response to >12m of therapy; two of these patients died of decompensated cirrhosis. 49 patients have achieved an end of treatment response (ETR) following a mean of 15m of therapy; of the remaining 21 OTVR pts, 20 remain on treatment while one has stopped due to adverse effects. Of the 49 ETR patients, 24 have achieved an SVR, 7 have relapsed and 18 are <6m post treatment discontinuation. 61% of patients have required growth factors. Rejection rate was 7%. Three patients who developed fibrosing cholestatic HCV within a year of tx are included, with 1 SVR, one OTVR still on treatment, and one non-responder who currently has decompensated cirrhosis 4y after transplant.

 

CONCLUSIONS

Combination therapy yields virological response in 70% of treated patients, similar to that described in non-transplant patients; requirements for growth factors are common. The optimal duration of therapy is unclear, although likely longer than in the non-transplant setting.