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S1008 Viral Load Predicts Outcome of Hepatitis C Patients After Liver Transplantation
and cold ischemic time for the rapid development to advanced fibrosis. Genotype, immunosuppression and several other parameters did not reach statistical significance. Our study shows that viral load is an important parameter for the development of severe recurrent disease and recipient survival after LT. Whereas early viremia is highly predictive for the cholestatic type, high viral loads between month 3 and 6 are associated with advanced fibrosis/cirrhosis of the liver allograft. S1009 Long-Term Treatment with Alfa-IFN in Hepatitits C Recurrence After OLT Federica Buonfiglioli, Maria Rosa Tamè, Francesca Lodato, Antonio Colecchia, Paolo Cecinato, Francesco Azzaroli, Valentina Feletti, Marco Vivarelli, Massimo Del Gaudio, Fabio Piscaglia, Enrico Roda, Antonio Pinna, Giuseppe Mazzella Background and Aim: Long term treatment effects of alfa-IFN and Ribavirin (RBV) on hepatitis C recurrence after liver transplant (OLT) are lacking. Primary end point of this study is to evaluate the effect of long term administration of alfa-IFN+RBV on histology, viral response, and survival according to severity. Material and Methods: 31 patients (19M, 12F; mean age 56.2±1.6 yrs; median time from OLT 10±6.3 months, 6 genotype 2, 22 genotype 1, and 3 genotype 4 ) were prospectively included in the protocol study. All patients received 3MU/day of alfa-IFN and 800 mg/day RBV with dose adjustment according to tolerability. Responders have been treated for further 12 months after viral clearance, non-responders (NR) continued treatment at the same dose. Liver biopsies were obtained at baseline, 18 and 30 months. Eleven patients had a severe HCV disease (SC-D) (5 fibrosing cholestatic relapse and 6 compensated liver cirrhosis) and 20 non cirrhotic disease (NC-D) (12 stage 1, 5 stage 2, 3 stage 3). MedCalc software package was used for statistical analysis. Results: The mean treatment time for SVR was 19.1±2.8 months, while for NR was 27.7±3.1 months (p<0.01). Nine (29%) patients had SVR (3 genotype 2 and 6 genotype 1) and 22 (71%) were NR. Survival probability of SC-D was 36% after 40 months of treatment while all NC-D were alive (p=0.01). A significant decrease of histology grading was observed after 18 months of therapy in both SC-D (from 9.6±1.3 to 5.8±1.1 p=0.004) and NC-D (from 5.9±0.6 to 3.7±0.5 p=0.0009), but significant decrease of histology stage was observed only in NC-D (from 1.65±0.19 to 1.3±0.16 p=0.03;). Viral load nadir was observed after 18 months both for SC-D (mean difference -3.07 Log , p=0.046) and NC-D (mean difference -3.47 Log, p=0.0002). Conclusion: Early long term treatment with alfa-IFN+RBV improves liver histology in NC-D regardless to viral persistence. Treatment of SC-D is less appealing because of disappointing results and side effects related to disease severity.
* HCV RNA undetected at time of event ** HCV RNA undetected when treatment discontinued
AASLD Abstracts
S1007 Genotype 2 and 3 Reccurent Hepatitis C After Liver Transplantation: Excellent Results with Suboptimal Doses of Antiviral Therapy Raffaella Viganò, Francesca R. Ponziani, Luca S. Belli, Marcello Vangeli, Giovambattista Pinzello, Antonio Gasbarrini, Luisa Pasulo, Eleonora De Martin, Patrizia Burra, Maurizio Pompili, Michele Colledan, Umberto Cillo, Stefano Fagiuoli Background and Aim. Recurrent hepatitis C after liver transplantation (OLTx) is a major problem. 50-80% of the patients will experience recurrent hepatitis C disease after transplant and, in the absence of antiviral therapy, about 30% will progress to cirrhosis within 5 years from grafting. Combined antiviral therapy is a well established therapeutic option in imunocompetent individuals but its efficacy in the liver transplant setting is strongly limited by side effects with current sustained virological response (SVR) rates ranging between 18 and 35%, well below to what can be usually achieved in immunocompetent subjects. Aim of this study is to report our experience of antiviral therapy in a large group of HCV recipient from 4 Italian Centers and more specifically to look for possible factors that influence treatment responses. Material and methods. 130 HCV recipients (38 female and 92 male) transplanted between 1999 through October 2007 received antiviral therapy for HCV recurrence. Genotype distribution was as follows: type 1=90, type 4a/4c= 4; type 2=26, type 3= 9, missing=1). Combined antiviral treatment was scheduled for 1 year in all genotypes and consisted of either recombinant-IFN or Peg-Interferon at standard dose with ribavirine at a variable dose according to the period of treatment and to protocol in use in the different centers. Results. 117 (84%) patients completed the antiviral course while 13 (16%) dropped out after a median time of 15 weeks for side effects. End of treatment virological response (EOT-VR) was obtained in 69/130 (53%) and was maintained 6 months after end of therapy (SVR) in 55 (42%). After univariate analysis (Fisher Test) only genotype, IFN dose and therapy duration were significantly associated with SVR (p<0.0001; p=0.0018, p<0.0001). In the subgroup of genotype 2 and 3 the EOT-VR and SVR were respectively 82.8% and 80%. These favourable results were obtained with mean ribavirine doses of 513 mg/daily and despite 40 % of the patients were treated for a period < 24 weeks. Notably, all genotype 2-3 patients treated for at least 24 weeks achieved SVR. Conclusion: In the liver transplant setting the results of antiviral therapy for genotype 2 and 3 are excellent despite suboptimal doses of drugs and short duration of therapy. Differently, genotype 1 and 4 are difficult to treat and treatment responses are almost half of that obtained in immunocompetent individuals.
S1010 Severe Recurrent Hepatitis C (SRHCV) Following Liver Transplantation (LT) Is Associated with Higher Rates of Anastomotic Strictures (AS) Roy Yen, James R. Burton, Daniel A. Ringold, Yang K. Chen, Norio Fukami, Brian C. Brauer, Raj J. Shah Background: Cholestasis and an immune-mediated response to HCV may contribute to the development of hepatic fibrosis and AS, respectively. It is unknown whether pts with SRHCV have higher rates of AS. Methods: We queried our transplant database for pts who underwent primary LT for HCV between 1/1/05 and 12/31/07. SRHCV was defined as >1 of the following within 1yr of LT: A) initiation of antiviral therapy, B) recurrent HCV on biopsy with either grade >3 inflammation or stage >2 fibrosis, or C) total bilirubin >6mg/dl and alk phos >5xULN within 30 days of biopsy with recurrent HCV. Sample LT data: age, gender, ethnicity, BMI, ABO group, listing MELD, HCV genotype, donor/graft characteristics, warm/ cold ischemia times, and immunosuppression regimen. ERCP data: AS, stricture dilation, and stenting. Chi square used to compare proportions; t-test used to compare means. Results: 173 HCV pts had LT during the study period of which 162 (75% male, mean age 52 yrs) were included for analysis (11 excluded for Roux-Y). 38/162 (23%) had >1 criteria for SRHCV (A=21, B=31, C=2), and 124/162 (77%) were non-SRHCV. LT characteristics for both groups were similar. Significantly more pts with SRHCV had ERCPs and AS (See Table). Each group had a similar mean: number of ERCPs per pt with AS, time from LT to AS, total outer diameter of stents prior to stent-free trial, number of AS dilations, and time to AS resolution (See Table). AS resolution was noted in 11/11 (100%) with SRHCV and 6/7 (86%) without SRHCV (p=.39). AS resolution could not be determined in 7/25 (28%) due to: death (1 SRHCV, 1 non-SRHCV), ongoing endotherapy (1 SRHCV, 2 non-SRHCV), and 2 non-SRHCV pts requiring surgery (total duct disruption, hepatic artery thrombosis). One non-SRHCV pt had recurrent AS treated with repeat endotherapy. Conclusions: 1) Patients with severe recurrent hepatitis C following liver transplantation had a higher rate of anastomotic strictures. Most were successfully treated by ERCP. 2) Cholestasis associated with anastomotic strictures may be a coexisting fibrogenic event that leads to more severe HCV recurrence. Larger, prospective studies are needed. Results
S1008 Viral Load Predicts Outcome of Hepatitis C Patients After Liver Transplantation Ivo Graziadei, Karin Nachbaur, Anna Schloegl, Karl Peter Pfeiffer, Walter Mark, Wolfgang Vogel Recurrent hepatitis C (HCV) infection is almost ubiquitous after liver transplantation (LT). Risk factors associated with HCV recurrence include donor, recipient and viral parameters. Conflicting data have been reported regarding viral load and severity of recurrent HCV disease. The aim of this study was to analyse the impact of viral load within the first year after LT on severity of recurrent HCV infection. Between 1980 and 2006 175 patients were transplanted due to HCV-cirrhosis at our institution. Only patients (n=128, age: 56.8±8.9 years; 31 females, 99 males) who survived more than 6 months and with histological assessment of recurrent HCV infection were included in this study. Non of the excluded patients died due to HCV recurrence. Viral loads were measured at week 2, month 3, 6 and 12 post LT, using the bDNA HCV RNA 3.0 assay (Bayer Diagnostics). 34 patients (18.4%) developed either a cholestatic type of HCV recurrence (n=16; 8.6%) and / or a rapid progression to advanced fibrosis / cirrhosis (n=23, 12.4%). The overall follow-up was 6.1 years. The actuarial patient survival of all patients at 1-, 5- and 10 years were 87%, 75% and 59%. Patients with cholestatic type recurrence and advanced fibrosis had significantly decreased survival rates at 1-, 5- and 10 years with 90%, 65% and 45%, compared to patients with mild/moderate or no recurrent disease with 98%, 81% and 71%. Cox regression analysis showed that the development of a cholestatic recurrence, patients' age and viral load at week 2 were associated with poor patient survival. Although higher viral loads were seen in patients with a severe recurrence at any time, multivariate binary regression analysis showed that only viremia at week 2 and donor age were predictive factors for the cholestatic HCV recurrence in contrast to viral loads at months 3 and 6 together with recipient age
AASLD Abstracts
A-812
* HCV RNA undetected at time of event ** HCV RNA undetected when treatment discontinued
AASLD Abstracts
S1007 Genotype 2 and 3 Reccurent Hepatitis C After Liver Transplantation: Excellent Results with Suboptimal Doses of Antiviral Therapy Raffaella Viganò, Francesca R. Ponziani, Luca S. Belli, Marcello Vangeli, Giovambattista Pinzello, Antonio Gasbarrini, Luisa Pasulo, Eleonora De Martin, Patrizia Burra, Maurizio Pompili, Michele Colledan, Umberto Cillo, Stefano Fagiuoli Background and Aim. Recurrent hepatitis C after liver transplantation (OLTx) is a major problem. 50-80% of the patients will experience recurrent hepatitis C disease after transplant and, in the absence of antiviral therapy, about 30% will progress to cirrhosis within 5 years from grafting. Combined antiviral therapy is a well established therapeutic option in imunocompetent individuals but its efficacy in the liver transplant setting is strongly limited by side effects with current sustained virological response (SVR) rates ranging between 18 and 35%, well below to what can be usually achieved in immunocompetent subjects. Aim of this study is to report our experience of antiviral therapy in a large group of HCV recipient from 4 Italian Centers and more specifically to look for possible factors that influence treatment responses. Material and methods. 130 HCV recipients (38 female and 92 male) transplanted between 1999 through October 2007 received antiviral therapy for HCV recurrence. Genotype distribution was as follows: type 1=90, type 4a/4c= 4; type 2=26, type 3= 9, missing=1). Combined antiviral treatment was scheduled for 1 year in all genotypes and consisted of either recombinant-IFN or Peg-Interferon at standard dose with ribavirine at a variable dose according to the period of treatment and to protocol in use in the different centers. Results. 117 (84%) patients completed the antiviral course while 13 (16%) dropped out after a median time of 15 weeks for side effects. End of treatment virological response (EOT-VR) was obtained in 69/130 (53%) and was maintained 6 months after end of therapy (SVR) in 55 (42%). After univariate analysis (Fisher Test) only genotype, IFN dose and therapy duration were significantly associated with SVR (p<0.0001; p=0.0018, p<0.0001). In the subgroup of genotype 2 and 3 the EOT-VR and SVR were respectively 82.8% and 80%. These favourable results were obtained with mean ribavirine doses of 513 mg/daily and despite 40 % of the patients were treated for a period < 24 weeks. Notably, all genotype 2-3 patients treated for at least 24 weeks achieved SVR. Conclusion: In the liver transplant setting the results of antiviral therapy for genotype 2 and 3 are excellent despite suboptimal doses of drugs and short duration of therapy. Differently, genotype 1 and 4 are difficult to treat and treatment responses are almost half of that obtained in immunocompetent individuals.
S1010 Severe Recurrent Hepatitis C (SRHCV) Following Liver Transplantation (LT) Is Associated with Higher Rates of Anastomotic Strictures (AS) Roy Yen, James R. Burton, Daniel A. Ringold, Yang K. Chen, Norio Fukami, Brian C. Brauer, Raj J. Shah Background: Cholestasis and an immune-mediated response to HCV may contribute to the development of hepatic fibrosis and AS, respectively. It is unknown whether pts with SRHCV have higher rates of AS. Methods: We queried our transplant database for pts who underwent primary LT for HCV between 1/1/05 and 12/31/07. SRHCV was defined as >1 of the following within 1yr of LT: A) initiation of antiviral therapy, B) recurrent HCV on biopsy with either grade >3 inflammation or stage >2 fibrosis, or C) total bilirubin >6mg/dl and alk phos >5xULN within 30 days of biopsy with recurrent HCV. Sample LT data: age, gender, ethnicity, BMI, ABO group, listing MELD, HCV genotype, donor/graft characteristics, warm/ cold ischemia times, and immunosuppression regimen. ERCP data: AS, stricture dilation, and stenting. Chi square used to compare proportions; t-test used to compare means. Results: 173 HCV pts had LT during the study period of which 162 (75% male, mean age 52 yrs) were included for analysis (11 excluded for Roux-Y). 38/162 (23%) had >1 criteria for SRHCV (A=21, B=31, C=2), and 124/162 (77%) were non-SRHCV. LT characteristics for both groups were similar. Significantly more pts with SRHCV had ERCPs and AS (See Table). Each group had a similar mean: number of ERCPs per pt with AS, time from LT to AS, total outer diameter of stents prior to stent-free trial, number of AS dilations, and time to AS resolution (See Table). AS resolution was noted in 11/11 (100%) with SRHCV and 6/7 (86%) without SRHCV (p=.39). AS resolution could not be determined in 7/25 (28%) due to: death (1 SRHCV, 1 non-SRHCV), ongoing endotherapy (1 SRHCV, 2 non-SRHCV), and 2 non-SRHCV pts requiring surgery (total duct disruption, hepatic artery thrombosis). One non-SRHCV pt had recurrent AS treated with repeat endotherapy. Conclusions: 1) Patients with severe recurrent hepatitis C following liver transplantation had a higher rate of anastomotic strictures. Most were successfully treated by ERCP. 2) Cholestasis associated with anastomotic strictures may be a coexisting fibrogenic event that leads to more severe HCV recurrence. Larger, prospective studies are needed. Results
S1008 Viral Load Predicts Outcome of Hepatitis C Patients After Liver Transplantation Ivo Graziadei, Karin Nachbaur, Anna Schloegl, Karl Peter Pfeiffer, Walter Mark, Wolfgang Vogel Recurrent hepatitis C (HCV) infection is almost ubiquitous after liver transplantation (LT). Risk factors associated with HCV recurrence include donor, recipient and viral parameters. Conflicting data have been reported regarding viral load and severity of recurrent HCV disease. The aim of this study was to analyse the impact of viral load within the first year after LT on severity of recurrent HCV infection. Between 1980 and 2006 175 patients were transplanted due to HCV-cirrhosis at our institution. Only patients (n=128, age: 56.8±8.9 years; 31 females, 99 males) who survived more than 6 months and with histological assessment of recurrent HCV infection were included in this study. Non of the excluded patients died due to HCV recurrence. Viral loads were measured at week 2, month 3, 6 and 12 post LT, using the bDNA HCV RNA 3.0 assay (Bayer Diagnostics). 34 patients (18.4%) developed either a cholestatic type of HCV recurrence (n=16; 8.6%) and / or a rapid progression to advanced fibrosis / cirrhosis (n=23, 12.4%). The overall follow-up was 6.1 years. The actuarial patient survival of all patients at 1-, 5- and 10 years were 87%, 75% and 59%. Patients with cholestatic type recurrence and advanced fibrosis had significantly decreased survival rates at 1-, 5- and 10 years with 90%, 65% and 45%, compared to patients with mild/moderate or no recurrent disease with 98%, 81% and 71%. Cox regression analysis showed that the development of a cholestatic recurrence, patients' age and viral load at week 2 were associated with poor patient survival. Although higher viral loads were seen in patients with a severe recurrence at any time, multivariate binary regression analysis showed that only viremia at week 2 and donor age were predictive factors for the cholestatic HCV recurrence in contrast to viral loads at months 3 and 6 together with recipient age
AASLD Abstracts
A-812