- Email: [email protected]
P0062 : Changes in cerebral hemodynamics in cirrhotic patients after liver transplantation
POSTERS depicted in the Table. No serious adverse events were observed. RBV reduction and/or epoetin administration was required in 25% of pts; 3 pts underwent blood transfusion and 3 were hospitalized due to complications of liver disease. Of the 7 pts transplanted until now, 4 had HCV RNA <15 IU/mL for a median of 62 days (31–91) and discontinued antiviral Tx at the time of LT. All those 4 pts are currently HCV RNA negative after a median follow-up post-LT of 45 days (16–69). Two pts underwent LT while still being HCV RNA positive after less than 4 weeks of Tx, and the last one was transplanted 3 days ago having HCV RNA <15 IU/mL since 5 days. Time point (No. of patients)
HCV RNA negative
HCV RNA <15 IU/mL
MELD score, median (range)
Child–Pugh score B (%)
C (%)
Basal (N = 24) Week 4 (N = 20) Week 8 (N = 14) Week 12 (N = 10) Week 16 (N = 7) Week 4 after LT (N = 3)
0% 50% 100% 100% 100% 100%
0% 75% 100% 100% 100% 100%
13 14 13 14 15
71% 33% 64% 40% 29%
17% 39% 21% 30% 20%
(7–19) (6–23) (7–18) (7–21) (9–21)
Conclusions: An all oral Tx with SOF plus RBV induces rapid HCV clearance and is well tolerated in cirrhotic pts awaiting LT. Preliminary post-LT SVR4 rate is promising in pts undergoing LT after at least 1 month from viral clearance. Further data will be presented as they become available. P0061 TREATMENT WITH NEW ALL-ORAL DIRECT ACTING ANTIVIRALS IN HCV-RECURRENCE IN LIVER TRANSPLANT-SETTING INDUCES A REDUCTION OF IMMUNOSUPPRESSIVE DRUG LEVELS J. Cabezas1,2 , M. Berenguer3 , J.M. Pascasio4 , M.-C. Londono ˜ 5, J.M. Sousa Mart´ın4 , C. Navascues ´ 6 , C. Vinaixa3 , I. Banos ˜ 7 , J.L. Calleja7 , M. Rodr´ıguez6 , X. Forns5 , J. Crespo1,2 . 1 Hepatology Unit, Digestive Service, University Hospital Marqu´es de Valdecilla, 2 Research Institute Valdecilla, IDIVAL, Santander, 3 Hepatology Unit and CIBERehd, University Hospital La Fe, Valencia, 4 Hepatology Unit, University Hospital Virgen del Roc´ıo, Sevilla, 5 Liver Unit, IDIBAPS and CIBERehd, Hospital Clinic, Barcelona, 6 Hepatology Unit, Hospital Universitario Central de Asturias, Oviedo, 7 Hepatology Unit, University Hospital Puerta de Hierro, Madrid, Spain E-mail: [email protected] Background and Aims: Introduction: New direct acting antiviral agents (DAA) are an important advance in HCV treatment. DAA combinations have shown high efficacy in difficult-to-treat patients. They are not supposed to have significant pharmacological interaction with immunosuppressants (IS), so they are good candidates to treat liver transplant (LT) patients. Aim: To describe efficacy and safety of DAA-treatments in patients with HCV-recurrence after LT. We focused our study in the potential immunosuppressant level reduction during DAA-treatment. Methods: We evaluated 71 LT patients under IFN-free DAA treatment, including 18 patients with fibrosis cholestatic hepatitis. We monitored them weekly the first month and then every 2 weeks. Results: 53 males. Patients’ mean age was 56 years old (range 41–74); Range time from LT 1–198 months. Genotype distribution: 1a, 8 patients; 1b, 55, and 5 genotype 3 and 3 patients genotype 4. Fibrosis evaluation of HCV recurrence (METAVIR): F <2, 23 patients; F3, 10; F4, 31. 52 treatment experienced. All patients were on a stable IS regimen: 50 tacrolimus, 12 cyclosporine and 9 with mTOR. Efficacy: 46/71 achieved RVR; and 58/70 achieved RNA undetectable at week 8, and 60/60 at week 12. Patients did not developed any significant adverse events. 2 deaths were reported, not related to antiviral treatment.
Mean IS level reduction was 30% (range 3–82%) between week 1 and 26 (mean 6). IS doses were adjusted in 42/65; 6/68 had an acute rejection. The majority of patients improved AST levels. 13/71 improved albumin level; 35/71 improved bilirubin level; and 21/71 improved INR. Almost all patients improved non-invasive fibrosis scores by week 4: APRI decreased a mean 3.5 (range 0.2–10.2), FORNS mean 1.8 (range 1.2–10.2), Fibroindex mean 0.9 (range 0.1–5.6) and Fib-4 mean 4.4 (range 0.7–19.5). IS level reduction correlates significantly with non-invasive scores improvement: Pearson values for APRI 0.41 (p = 0.005); FORNS 0.55 (p < 0.0001); Fibroindex 0.45 (p = 0.05) and Fib-4 0.32 (p = 0.038). 37/71 patients improved MELD score between 1 and 17 points. Conclusions: All-oral DAA combinations have a high viral efficacy with an excellent safety profile in LT patients. Despite the absence of a pharmacological interaction we have observed a decrease in immunosuppression levels, this could be related to a quick liver function recovery that improves IS clearance. In these patients, it would be recommended to closely monitor immunosuppression levels. P0062 CHANGES IN CEREBRAL HEMODYNAMICS IN CIRRHOTIC PATIENTS AFTER LIVER TRANSPLANTATION R.U. Macias-Rodriguez1 , O. Garc´ıa Flores1 , A. Ruiz-Margain1 , 2 C. Cantu-Brito ´ , A. Torre1 . 1 Department of Gastroenterology, 2 Department of Neurology, Instituto Nacional de Ciencias M´edicas y Nutrici´ on “Salvador Zubir´ an”, Mexico City, Mexico E-mail: [email protected] Background and Aims: Changes in cerebral hemodynamics before and during liver transplantation (LT) have been related to poor neurological outcomes after LT. Improvement in cognitive function after LT has been related to decreased cerebral white matter lesions induced by microvascular lesions (leukoaraiosis) secondary to lowgrade cerebral edema. However most of studies have addressed these changes in the acute setting during and immediately after LT in cirrhosis as well as in acute liver failure and few have evaluated the long-term changes in cerebral hemodynamics in this population, therefore we aimed to investigate the long-term changes on cerebral hemodynamics in cirrhotic patients after LT. Methods: This was a prospective cohort study. Patients were evaluated by Transcranial Doppler Ultrasonography (TCD) obtaining Pulsatility index (PI) a marker of cerebrovascular structural integrity and breath-holding index (BHI) a marker of cerebrovascular reactivity which were measured in the middle cerebral artery pre and post-LT. Critical flicker frequency (CFF), psychometric hepatic encephalopathy score (PHES) and West-Haven criteria were used for HE characterization. Mean follow up after LT was 6 months. Results: We included 17 patients (11 males); median age preLT was 45 (40–53) years, major etiology was hepatitis C virus (8/17), most of patients were Child–Pugh B (12/17), MELD score was 15.5 (12–17.5), MELD-Na 18, PHES −3 and CFF 38.5 Hz. Previous to the LT 11/17 patients had HE (6/4/1; covert, grade I and grade II HE, respectively), 5/17 ascites and 5/17 hepatocellular carcinoma. A decrease in PI was observed in all patients after LT and an increase in BHI in 9/17 (PI 1.01 and BHI 0.77 pre-LT vs PI 0.78 and BHI 0.72 post-LT, P < 0.001 and 0.740, respectively). The change on PI corresponds to a decrease of 22% and an increase on BHI of 55% after LT. Clinical improvement in cognition was observed in all patients with overt HE after LT. Conclusions: These results show an improvement in cerebral hemodynamics at long-term after LT in cirrhosis, indicating less arterial cerebral vasoconstriction (decrease in PI) and an improvement in cerebrovascular autoregulation in 9/17 patients (increase in BHI). This could explain the improvement in cognitive function after LT and the decrease in cerebral white matter lesions induced by microvascular lesions described in some studies. TCD
Journal of Hepatology 2015 vol. 62 | S263–S864
S315
POSTERS could be considered as a useful tool for the assessment of the changes in cerebral hemodynamics pre and post-LT in cirrhosis. P0063 SOFOSBUVIR PLUS RIBAVIRIN FOR THE TREATMENT OF SEVERE HCV RECURRENCE AFTER LIVER TRANSPLANTATION: PRELIMINARY DATA FROM A SINGLE-CENTRE EXPERIENCE S. Marco1 , S. Martini1 , S. Strona1 , D. Arese1 , D. Cocchis2 , S. Mirabella2 , G. Rizza2 , F. Tandoi2 , R. Romagnoli2 , A. Ottobrelli1 , M.R. Torrani Cerenzia1 , F. Balzola1 , M. Salizzoni2 , M. Rizzetto1 . 1 Gastrohepatology Unit, 2 Liver Transplant Centre, General Surgery, A.O.U. Citt` a della Salute e della Scienza di Torino, Torino, Italy E-mail: [email protected] Background and Aims: Recurrent hepatitis occurs in the vast majority of HCV-positive recipients who are viremic at the time of liver transplantation (LT). We evaluated safety and efficacy of all oral antiviral therapy (Tx) with sofosbuvir (SOF) plus ribavirin (RBV) in a population of HCV-infected patients (pts) having severe recurrent hepatitis after LT. Methods: Among HCV viremic pts transplanted in our Centre since 2000, we enrolled to date 107 pts affected by HCV RNApositive recurrent hepatitis with fibrosis score F3 (21 pts) or F4 (86 pts) according to Metavir. 78% male, mean age 60.5 years, mean BMI 24.7; 49% are receiving cyclosporine, 43% mycophenolate, 38% tacrolimus and 3% m-TOR inhibitors. GT1 75% (GT1a 13%), GT2 5%, GT3 15%, GT4 5%; IL28 CC 24%; 65% had prior HCV Tx. According to compassionate use, pts receive SOF 400 mg/die plus RBV (weightbased: 1000 mg daily if <75 kg; 1200 mg daily if ≥75 kg) for 24 weeks. Median time from LT to Tx 4.96 years (0.25–14.25); mean baseline HCV RNA 6.62 log10 IU/mL (3.4–7.9 log10 IU/mL); mean GFR 76 mL/min. Time point (No. of patients)
HCV RNA HCV RNA
Mean Hb Mean GFR MELD score,
Child
negative <15 IU/mL (g/dL)
(mL/min)
median (range) score
Basal (N = 107)
0%
0%
12.8
76
12 (6–22)
26%
5%
Week 4 (N = 98)
51%
88%
11.1
75
12 (6–26)
22%
6%
Week 8 (N = 77)
99%
100%
10.2
75
12 (6–22)
23%
6%
Week 12 (N = 31)
100%
100%
10.8
75
13 (6–28)
29%
13%
Week 16 (N = 9)
100%
100%
10.5
87
8 (6–18)
44%
11%
Week 24 (N = 2)
100%
100%
11.4
101
12 and 14
A6 and B7
50%
12.6
102
11 and 16
A5 and B9
B (%) C (%)
Week 4 after end of Tx (N = 2) 50% Hb, haemoglobin.
Results: Until now, 31/107 pts completed 12 weeks of Tx. After 1 week of Tx, median decrease in HCV RNA was 3.61 log10 IU/mL; 50/98 (51%) at week 4 and 76/77 (99%) at week 8 were HCV RNA negative. Other results available until now are shown in the Table. Of the 2 pts who completed the planned therapy and reached 4 weeks post-Tx, one relapsed; he is IL28 TT, GT1a and the only one who tested HCV RNA <15 IU/mL at week 8 on Tx. The most common adverse events were fatigue, headache and nausea. During Tx, 1 patient had variceal bleeding (day 78) and 1 died due to multiorgan failure (day 86); 25% received blood transfusion or epoetin; 1 patient temporally discontinued RBV because of skin rash. Minimal immunosuppression dose adjustments were required on Tx and no rejection episodes were recorded. Conclusions: In pts with severe HCV recurrence post-LT, an all oral antiviral regimen using SOF plus RBV is very well tolerated and easy to manage, while allowing rapid HCV clearance. Data on sustained virologic response will be presented as they become available.
P0064 RIBAVIRIN PRE-TREATMENT IN LIVER TRANSPLANT PATIENTS WITH HCV RECURRENCE: RESULTS FROM PEARL MULTICENTRE RANDOMIZED TRIAL V. Giannelli1 , A. Zanetto2 , P. Burra3 , P.R. Francesca4 , A. Gasbarrini4 , U.V. Comandini5 , G.M. Ettorre5 , M. Giusto1 , E. Biliotti1 , M. Merli1 , G. Taliani1 . 1 Sapienza University of Rome, Rome, 2 University of Padova, Padova, 3 University of Padova, 4 Catholic University, 5 POIT, Rome, Italy E-mail: [email protected] Background and Aims: The treatment of liver transplanted patients with HCV recurrence is still a critical issue as the antiviral treatment regime based on the new DAA is not universally available and, due to high cost, restricted to patients with moderate/severe fibrosis (F≥3). In a previous pilot uncontrolled study we showed that 8-week ribavirin (RBV) pre-treatment before standard antiviral therapy with RBV and PEG-IFN, exhibits a better safety profile and therapy outcome in liver transplant patients with HCV recurrence. We aimed at further verify our hypothesis through a multicenter randomized controlled study (clinicaltrial.gov: NCT00993122). Methods: The study is a multicentre prospective randomized controlled trial comparing 8-weeks RBV treatment followed by 48 weeks of PegIFN-Riba (PR) therapy vs. 48 weeks of PR. Riba and PEG-IFN2b and were given according to the EASL guidelines. Randomization was stratified for HCV genotype. 4 Italian centers participate in patients enrollment according to the inclusion and exclusion criteria starting from 2011 for a consecutive period. Inclusion criteria were: post-transplant HCV recurrence observed at least 6 months after liver transplant. Patients were excluded if they failed to meet the standard eligibility criteria for PEG-IFN/RBV treatment. IL28B polymorphism was also examined. Results: Forty-nine patients were randomized 1:1 to RBV pretreatment (pre-treatment group) or PEG-IFN2b (standard group). Liver biopsy prior to therapy showed moderate fibrosis (F <2) in 54% of patients and severe fibrosis (F >3) in 46%. HCV genotype were 1b 78% and non-1 22%. During RBV pre-treatment, HCV RNA showed a decline of 0.64 log10 IU/mL compared to pre-treatment level (P < 0.003) that was unrelated to the IL28B rs12979860 genotype (CC vs CT/TT, P = 0.320). The rate of rapid virological response (RVR) was significantly higher in the RBV pre-treatment arm compared to the standard treatment arm (P = 0.040) while the SVR rate was similar (48% and 43%, respectively; p > 0.300). However, the risk to develop severe therapy-related side effects and the need for supportive therapy was higher in the standard compared to the pre-treatment arm (32 vs 18%, respectively; P = 0.042). Conclusions: In conclusion, RBV pre-treatment showed a significant antiviral activity independent to fibrosis at baseline or IL28 genotype. Although RBV pre-treatment failed to achieve a better outcome (SVR), the reduced incidence of serious adverse events might favor this option. P0065 EFFECT OF PORTAL VEIN THROMBOSIS (PVT) ON SURVIVAL AFTER LIVER TRANSPLANTATION (LT): A METANALYSIS A. Zanetto1 , K.-I. Rodriguez-Castro1 , E. Nadal1 , A. Ferrarese1 , G. Germani1 , F.P. Russo1 , P. Burra1 , M. Senzolo1 . 1 Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy E-mail: [email protected] Background and Aims: Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis undergoing liver transplant (LT). Although PVT is no longer considered an absolute controindication to LT, published data of its effect on mortality after the surgery are heterogeneous and discordant. The aim of the present study was to systematically review the current literature on the role of PVT in LT recipients in term of outcome.
S316
Journal of Hepatology 2015 vol. 62 | S263–S864
HCV RNA negative
HCV RNA <15 IU/mL
MELD score, median (range)
Child–Pugh score B (%)
C (%)
Basal (N = 24) Week 4 (N = 20) Week 8 (N = 14) Week 12 (N = 10) Week 16 (N = 7) Week 4 after LT (N = 3)
0% 50% 100% 100% 100% 100%
0% 75% 100% 100% 100% 100%
13 14 13 14 15
71% 33% 64% 40% 29%
17% 39% 21% 30% 20%
(7–19) (6–23) (7–18) (7–21) (9–21)
Conclusions: An all oral Tx with SOF plus RBV induces rapid HCV clearance and is well tolerated in cirrhotic pts awaiting LT. Preliminary post-LT SVR4 rate is promising in pts undergoing LT after at least 1 month from viral clearance. Further data will be presented as they become available. P0061 TREATMENT WITH NEW ALL-ORAL DIRECT ACTING ANTIVIRALS IN HCV-RECURRENCE IN LIVER TRANSPLANT-SETTING INDUCES A REDUCTION OF IMMUNOSUPPRESSIVE DRUG LEVELS J. Cabezas1,2 , M. Berenguer3 , J.M. Pascasio4 , M.-C. Londono ˜ 5, J.M. Sousa Mart´ın4 , C. Navascues ´ 6 , C. Vinaixa3 , I. Banos ˜ 7 , J.L. Calleja7 , M. Rodr´ıguez6 , X. Forns5 , J. Crespo1,2 . 1 Hepatology Unit, Digestive Service, University Hospital Marqu´es de Valdecilla, 2 Research Institute Valdecilla, IDIVAL, Santander, 3 Hepatology Unit and CIBERehd, University Hospital La Fe, Valencia, 4 Hepatology Unit, University Hospital Virgen del Roc´ıo, Sevilla, 5 Liver Unit, IDIBAPS and CIBERehd, Hospital Clinic, Barcelona, 6 Hepatology Unit, Hospital Universitario Central de Asturias, Oviedo, 7 Hepatology Unit, University Hospital Puerta de Hierro, Madrid, Spain E-mail: [email protected] Background and Aims: Introduction: New direct acting antiviral agents (DAA) are an important advance in HCV treatment. DAA combinations have shown high efficacy in difficult-to-treat patients. They are not supposed to have significant pharmacological interaction with immunosuppressants (IS), so they are good candidates to treat liver transplant (LT) patients. Aim: To describe efficacy and safety of DAA-treatments in patients with HCV-recurrence after LT. We focused our study in the potential immunosuppressant level reduction during DAA-treatment. Methods: We evaluated 71 LT patients under IFN-free DAA treatment, including 18 patients with fibrosis cholestatic hepatitis. We monitored them weekly the first month and then every 2 weeks. Results: 53 males. Patients’ mean age was 56 years old (range 41–74); Range time from LT 1–198 months. Genotype distribution: 1a, 8 patients; 1b, 55, and 5 genotype 3 and 3 patients genotype 4. Fibrosis evaluation of HCV recurrence (METAVIR): F <2, 23 patients; F3, 10; F4, 31. 52 treatment experienced. All patients were on a stable IS regimen: 50 tacrolimus, 12 cyclosporine and 9 with mTOR. Efficacy: 46/71 achieved RVR; and 58/70 achieved RNA undetectable at week 8, and 60/60 at week 12. Patients did not developed any significant adverse events. 2 deaths were reported, not related to antiviral treatment.
Mean IS level reduction was 30% (range 3–82%) between week 1 and 26 (mean 6). IS doses were adjusted in 42/65; 6/68 had an acute rejection. The majority of patients improved AST levels. 13/71 improved albumin level; 35/71 improved bilirubin level; and 21/71 improved INR. Almost all patients improved non-invasive fibrosis scores by week 4: APRI decreased a mean 3.5 (range 0.2–10.2), FORNS mean 1.8 (range 1.2–10.2), Fibroindex mean 0.9 (range 0.1–5.6) and Fib-4 mean 4.4 (range 0.7–19.5). IS level reduction correlates significantly with non-invasive scores improvement: Pearson values for APRI 0.41 (p = 0.005); FORNS 0.55 (p < 0.0001); Fibroindex 0.45 (p = 0.05) and Fib-4 0.32 (p = 0.038). 37/71 patients improved MELD score between 1 and 17 points. Conclusions: All-oral DAA combinations have a high viral efficacy with an excellent safety profile in LT patients. Despite the absence of a pharmacological interaction we have observed a decrease in immunosuppression levels, this could be related to a quick liver function recovery that improves IS clearance. In these patients, it would be recommended to closely monitor immunosuppression levels. P0062 CHANGES IN CEREBRAL HEMODYNAMICS IN CIRRHOTIC PATIENTS AFTER LIVER TRANSPLANTATION R.U. Macias-Rodriguez1 , O. Garc´ıa Flores1 , A. Ruiz-Margain1 , 2 C. Cantu-Brito ´ , A. Torre1 . 1 Department of Gastroenterology, 2 Department of Neurology, Instituto Nacional de Ciencias M´edicas y Nutrici´ on “Salvador Zubir´ an”, Mexico City, Mexico E-mail: [email protected] Background and Aims: Changes in cerebral hemodynamics before and during liver transplantation (LT) have been related to poor neurological outcomes after LT. Improvement in cognitive function after LT has been related to decreased cerebral white matter lesions induced by microvascular lesions (leukoaraiosis) secondary to lowgrade cerebral edema. However most of studies have addressed these changes in the acute setting during and immediately after LT in cirrhosis as well as in acute liver failure and few have evaluated the long-term changes in cerebral hemodynamics in this population, therefore we aimed to investigate the long-term changes on cerebral hemodynamics in cirrhotic patients after LT. Methods: This was a prospective cohort study. Patients were evaluated by Transcranial Doppler Ultrasonography (TCD) obtaining Pulsatility index (PI) a marker of cerebrovascular structural integrity and breath-holding index (BHI) a marker of cerebrovascular reactivity which were measured in the middle cerebral artery pre and post-LT. Critical flicker frequency (CFF), psychometric hepatic encephalopathy score (PHES) and West-Haven criteria were used for HE characterization. Mean follow up after LT was 6 months. Results: We included 17 patients (11 males); median age preLT was 45 (40–53) years, major etiology was hepatitis C virus (8/17), most of patients were Child–Pugh B (12/17), MELD score was 15.5 (12–17.5), MELD-Na 18, PHES −3 and CFF 38.5 Hz. Previous to the LT 11/17 patients had HE (6/4/1; covert, grade I and grade II HE, respectively), 5/17 ascites and 5/17 hepatocellular carcinoma. A decrease in PI was observed in all patients after LT and an increase in BHI in 9/17 (PI 1.01 and BHI 0.77 pre-LT vs PI 0.78 and BHI 0.72 post-LT, P < 0.001 and 0.740, respectively). The change on PI corresponds to a decrease of 22% and an increase on BHI of 55% after LT. Clinical improvement in cognition was observed in all patients with overt HE after LT. Conclusions: These results show an improvement in cerebral hemodynamics at long-term after LT in cirrhosis, indicating less arterial cerebral vasoconstriction (decrease in PI) and an improvement in cerebrovascular autoregulation in 9/17 patients (increase in BHI). This could explain the improvement in cognitive function after LT and the decrease in cerebral white matter lesions induced by microvascular lesions described in some studies. TCD
Journal of Hepatology 2015 vol. 62 | S263–S864
S315
POSTERS could be considered as a useful tool for the assessment of the changes in cerebral hemodynamics pre and post-LT in cirrhosis. P0063 SOFOSBUVIR PLUS RIBAVIRIN FOR THE TREATMENT OF SEVERE HCV RECURRENCE AFTER LIVER TRANSPLANTATION: PRELIMINARY DATA FROM A SINGLE-CENTRE EXPERIENCE S. Marco1 , S. Martini1 , S. Strona1 , D. Arese1 , D. Cocchis2 , S. Mirabella2 , G. Rizza2 , F. Tandoi2 , R. Romagnoli2 , A. Ottobrelli1 , M.R. Torrani Cerenzia1 , F. Balzola1 , M. Salizzoni2 , M. Rizzetto1 . 1 Gastrohepatology Unit, 2 Liver Transplant Centre, General Surgery, A.O.U. Citt` a della Salute e della Scienza di Torino, Torino, Italy E-mail: [email protected] Background and Aims: Recurrent hepatitis occurs in the vast majority of HCV-positive recipients who are viremic at the time of liver transplantation (LT). We evaluated safety and efficacy of all oral antiviral therapy (Tx) with sofosbuvir (SOF) plus ribavirin (RBV) in a population of HCV-infected patients (pts) having severe recurrent hepatitis after LT. Methods: Among HCV viremic pts transplanted in our Centre since 2000, we enrolled to date 107 pts affected by HCV RNApositive recurrent hepatitis with fibrosis score F3 (21 pts) or F4 (86 pts) according to Metavir. 78% male, mean age 60.5 years, mean BMI 24.7; 49% are receiving cyclosporine, 43% mycophenolate, 38% tacrolimus and 3% m-TOR inhibitors. GT1 75% (GT1a 13%), GT2 5%, GT3 15%, GT4 5%; IL28 CC 24%; 65% had prior HCV Tx. According to compassionate use, pts receive SOF 400 mg/die plus RBV (weightbased: 1000 mg daily if <75 kg; 1200 mg daily if ≥75 kg) for 24 weeks. Median time from LT to Tx 4.96 years (0.25–14.25); mean baseline HCV RNA 6.62 log10 IU/mL (3.4–7.9 log10 IU/mL); mean GFR 76 mL/min. Time point (No. of patients)
HCV RNA HCV RNA
Mean Hb Mean GFR MELD score,
Child
negative <15 IU/mL (g/dL)
(mL/min)
median (range) score
Basal (N = 107)
0%
0%
12.8
76
12 (6–22)
26%
5%
Week 4 (N = 98)
51%
88%
11.1
75
12 (6–26)
22%
6%
Week 8 (N = 77)
99%
100%
10.2
75
12 (6–22)
23%
6%
Week 12 (N = 31)
100%
100%
10.8
75
13 (6–28)
29%
13%
Week 16 (N = 9)
100%
100%
10.5
87
8 (6–18)
44%
11%
Week 24 (N = 2)
100%
100%
11.4
101
12 and 14
A6 and B7
50%
12.6
102
11 and 16
A5 and B9
B (%) C (%)
Week 4 after end of Tx (N = 2) 50% Hb, haemoglobin.
Results: Until now, 31/107 pts completed 12 weeks of Tx. After 1 week of Tx, median decrease in HCV RNA was 3.61 log10 IU/mL; 50/98 (51%) at week 4 and 76/77 (99%) at week 8 were HCV RNA negative. Other results available until now are shown in the Table. Of the 2 pts who completed the planned therapy and reached 4 weeks post-Tx, one relapsed; he is IL28 TT, GT1a and the only one who tested HCV RNA <15 IU/mL at week 8 on Tx. The most common adverse events were fatigue, headache and nausea. During Tx, 1 patient had variceal bleeding (day 78) and 1 died due to multiorgan failure (day 86); 25% received blood transfusion or epoetin; 1 patient temporally discontinued RBV because of skin rash. Minimal immunosuppression dose adjustments were required on Tx and no rejection episodes were recorded. Conclusions: In pts with severe HCV recurrence post-LT, an all oral antiviral regimen using SOF plus RBV is very well tolerated and easy to manage, while allowing rapid HCV clearance. Data on sustained virologic response will be presented as they become available.
P0064 RIBAVIRIN PRE-TREATMENT IN LIVER TRANSPLANT PATIENTS WITH HCV RECURRENCE: RESULTS FROM PEARL MULTICENTRE RANDOMIZED TRIAL V. Giannelli1 , A. Zanetto2 , P. Burra3 , P.R. Francesca4 , A. Gasbarrini4 , U.V. Comandini5 , G.M. Ettorre5 , M. Giusto1 , E. Biliotti1 , M. Merli1 , G. Taliani1 . 1 Sapienza University of Rome, Rome, 2 University of Padova, Padova, 3 University of Padova, 4 Catholic University, 5 POIT, Rome, Italy E-mail: [email protected] Background and Aims: The treatment of liver transplanted patients with HCV recurrence is still a critical issue as the antiviral treatment regime based on the new DAA is not universally available and, due to high cost, restricted to patients with moderate/severe fibrosis (F≥3). In a previous pilot uncontrolled study we showed that 8-week ribavirin (RBV) pre-treatment before standard antiviral therapy with RBV and PEG-IFN, exhibits a better safety profile and therapy outcome in liver transplant patients with HCV recurrence. We aimed at further verify our hypothesis through a multicenter randomized controlled study (clinicaltrial.gov: NCT00993122). Methods: The study is a multicentre prospective randomized controlled trial comparing 8-weeks RBV treatment followed by 48 weeks of PegIFN-Riba (PR) therapy vs. 48 weeks of PR. Riba and PEG-IFN2b and were given according to the EASL guidelines. Randomization was stratified for HCV genotype. 4 Italian centers participate in patients enrollment according to the inclusion and exclusion criteria starting from 2011 for a consecutive period. Inclusion criteria were: post-transplant HCV recurrence observed at least 6 months after liver transplant. Patients were excluded if they failed to meet the standard eligibility criteria for PEG-IFN/RBV treatment. IL28B polymorphism was also examined. Results: Forty-nine patients were randomized 1:1 to RBV pretreatment (pre-treatment group) or PEG-IFN2b (standard group). Liver biopsy prior to therapy showed moderate fibrosis (F <2) in 54% of patients and severe fibrosis (F >3) in 46%. HCV genotype were 1b 78% and non-1 22%. During RBV pre-treatment, HCV RNA showed a decline of 0.64 log10 IU/mL compared to pre-treatment level (P < 0.003) that was unrelated to the IL28B rs12979860 genotype (CC vs CT/TT, P = 0.320). The rate of rapid virological response (RVR) was significantly higher in the RBV pre-treatment arm compared to the standard treatment arm (P = 0.040) while the SVR rate was similar (48% and 43%, respectively; p > 0.300). However, the risk to develop severe therapy-related side effects and the need for supportive therapy was higher in the standard compared to the pre-treatment arm (32 vs 18%, respectively; P = 0.042). Conclusions: In conclusion, RBV pre-treatment showed a significant antiviral activity independent to fibrosis at baseline or IL28 genotype. Although RBV pre-treatment failed to achieve a better outcome (SVR), the reduced incidence of serious adverse events might favor this option. P0065 EFFECT OF PORTAL VEIN THROMBOSIS (PVT) ON SURVIVAL AFTER LIVER TRANSPLANTATION (LT): A METANALYSIS A. Zanetto1 , K.-I. Rodriguez-Castro1 , E. Nadal1 , A. Ferrarese1 , G. Germani1 , F.P. Russo1 , P. Burra1 , M. Senzolo1 . 1 Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy E-mail: [email protected] Background and Aims: Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis undergoing liver transplant (LT). Although PVT is no longer considered an absolute controindication to LT, published data of its effect on mortality after the surgery are heterogeneous and discordant. The aim of the present study was to systematically review the current literature on the role of PVT in LT recipients in term of outcome.
S316
Journal of Hepatology 2015 vol. 62 | S263–S864