- Email: [email protected]
let-7d RATIO, HEPATITIS C VIRUS LOAD AND FIBROSING CHOLESTATIC HCV RECURRENCE AFTER LIVER TRANSPLANTATION
POSTERS Methods: Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature. Results: The search identified 62 citations. Four studies, with 430 patients, met eligibility criteria. The use of DCD livers was significantly associated with decreased graft survival (RR 0.44; 95% CI 0.24–0.79; p = 0.006; I2 =0%) and increased primary nonfunction (RR 5.49; 95% CI 1.53–19.64; p = 0.009; I2 =0%), while not significantly associated with a difference in patient survival (RR 0.78; 95% CI 0.40–1.55; p = 0.48; I2 =45%), rate of recurrence of severe HCV (RR 2.16; 95% CI 0.69–6.72; p = 0.19; I2 =69%), re-transplantation or liver-related death (RR 1.79; 95% CI 0.66–4.84; p = 0.25; I2 =44%), biliary leaks (RR 2.22; 95% CI 0.42–11.88; p = 0.35; I2 =35%), biliary strictures (RR 1.15; 95% CI 0.59–2.26; p = 0.68; I2 =0), and ischemic cholaniopathy (RR 6.67; 95% CI 0.84–52.66; p = 0.07; I2 =35%). Conclusions: DCD grafts are associated with decreased graft survival and increased primary non-function in patients with HCV. While the literature has limitations, this field is evolving. P878 MULTIVARIATE ANALYSIS OF FACTORS INFLUENCING SUSTAINED VIROLOGICAL RESPONSE RATE OF PROTEASE INHIBITOR-BASED TREATMENT FOR RECURRENT HCV GENOTYPE 1 AFTER LIVER TRANSPLANTATION: MULTICENTER EXPERIENCE S. Pungpapong1 , B. Aqel2 , M. Charlton3 , H. Vargas2 , A. Keaveny1 . 1 Mayo Clinic, Jacksonville, FL, 2 Mayo Clinic, Scottsdale, AZ, 3 Intermountain Medical Center, Murray, UT, United States E-mail: [email protected] Background and Aims: Preliminary reports suggested that combining telaprevir (TVR) or boceprevir (BOC) with peginterferon/ribavirin (PR) to treat recurrent HCV genotype 1 after liver transplantation (LT) increased sustained virological response (SVR) rates compared to PR therapy, but was associated with multiple adverse events. Factors influencing treatment outcomes remain undefined. Methods: Three large-volume transplant centers treated 101 LT recipients for recurrent HCV genotype 1, of which, 70 were treated with TVR+PR12/PR36, while 31 were treated with PR4/BOC+PR44. Prospectively collected data were subjected to univariate and multivariate analyses to identify factors influencing SVR 12 weeks after treatment discontinuation (SVR12). Results: Overall, 68% were male, 25% were non-Caucasian, 68% had genotype 1a, 49% had F3–4, 85% had IL28B CT/TT, 87% previously failed PR, and 13% had cholestatic recurrence. There were no differences in demographics, HCV, and LT-related factors between 2 cohorts. Fewer patients in TVR-cohort vs. BOCcohort prematurely discontinued treatment due to adverse events (20% vs. 42%, p = 0.03). More patients in TVR-cohort achieved undetectable HCV RNA (91% vs. 57% in BOC-cohort, p < 0.01). Viral breakthrough/relapse occurred at a comparable rate (TVR 22% vs. BOC 27%, p = 0.6). Of 82 patients who were followed >12 weeks after treatment discontinuation, SVR12 was achieved in 63% and 30% of TVR- and BOC-cohorts, respectively (p < 0.01). Univariate and multivariate analyses to identify factors influencing treatment failure were performed (table). PR doses reduction and/or growth factors administration did not influence SVR rates. Table: Factors influencing treatment failure Factor
Female gender Non-Caucasian METAVIR stage F3–4 Recipient IL28b CT/TT Genotype 1a Prior PR failure HCV RNA >800,000 IU/mL BOC (vs. TVR)
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Univariate analysis
Multivariate analysis
OR (95% CI)
P value
OR (95% CI)
P value
2.0 (0.8–5.0) 1.5 (0.5–4.4) 1.5 (0.6–3.5) 0.5 (0.1–2.1) 2.0 (0.8–5.2) 2.5 (0.6–10.3) 1.6 (0.5–5.5) 4.0 (1.5–10.6)
0.2 0.6 0.5 0.5 0.2 0.3 0.6 <0.01
3.1 (1.1–8.8)
0.03 NS NS NS NS NS NS 0.02
3.6 (1.2–10.9)
Conclusions: Our multicenter experience found higher SVR12 rates in TVR- compared with BOC-based treatment, partly because of fewer premature treatment discontinuations with TVR. P879 CIRCULATING miRNA-122/let-7d RATIO, HEPATITIS C VIRUS LOAD AND FIBROSING CHOLESTATIC HCV RECURRENCE AFTER LIVER TRANSPLANTATION A. Finkenstedt1 , S. Lechner1 , N. Baumgartner1 , J. Pratschke2 , I. Graziadei3 , W. Vogel1 , H. Zoller1 . 1 Department of Medicine II – Gastroenterology and Hepatology, 2 Department of Transplant Surgery, Medical University of Innsbruck, Innsbruck, 3 Department of Internal Medicine, Academic Teaching Hospital Hall in Tirol, Hall i. T., Austria E-mail: armin.fi[email protected] Background and Aims: Micro RNA 122 (miRNA-122) accounts for 70% of all hepatocellular micro RNA sequences and is essential for the replication of HCV. The aim of the study was to assess if miRNA122 concentrations two weeks after liver transplantation (LT) are predictive for fibrosing cholestatic HCV recurrence (FCH). Methods: The accuracy of serum miRNA-122 quantification critically depends on proper normalization with a stably expressed endogenous control. We therefore normalized the results with the best available internal normalizer let-7d. Micro RNA was extracted from serum samples using the Qiagen mirNeasy mini kit and miRNA-122 and let-7d were quantified by reverse transcription quantitative real-time PCR using TaqMan assays. Results: The study included 84 patients (68 men, mean age 55 years) who underwent LT for chronic HCV. In accordance with previous studies, let-7d normalized miRNA-122 was positively correlated with AST (r = 0.435; p < 0.001), ALT (r = 0.408; p < 0.001), gamma GT (r = 0.486; p < 0.001) and LDH (r = 0.481; p < 0.001). In contrast, miRNA-122 was not correlated with hepatitis C viral load at week 2. During follow-up, 12 patients developed fibrosing cholestatic HCV recurrence. miRNA-122 serum concentrations at week 2 after LT did not differ between patients with and without cholestatic recurrence. Conclusions: Normalized circulating miRNA-122 is not predictive for fibrosing cholestatic HCV recurrence. The moderate correlation of serum transaminase activities and miRNA-122 probably reflects the place of serum miRNA-122 in clinical hepatology: a sophisticated marker of hepatocellular integrity. P880 TERTIARY CENTRE EXPERIENCE OF THE SAFETY AND EFFICACY OF ANTI-TNFS FOR ULCERATIVE COLITIS (UC) AFTER LIVER TRANSPLANTATION A. Barnabas1 , J. Potts2 , K. Agarwal3 , B. Hayee2 . 1 King’s College Hospital, 2 Dept of Gastroenterology, 3 Institute for Liver Studies, King’s College Hospital, London, United Kingdom E-mail: [email protected] Background and Aims: Most patients with primary sclerosing cholangitis (PSC) have UC, which is usually mild in advanced PSC. However colitis may paradoxically worsen in up to 50% of patients following orthotopic liver transplantation (OLT), necessitating immunomodulator therapy. We reviewed our unit’s experience with anti-TNF agents post-OLT. Methods: A retrospective casenote review was performed of patients treated with anti-TNF agents post-OLT for colitis. Results: Eight patients (2 F) were identified; six with PSC-UC and one with autoimmune sclerosing cholangitis and UC received infliximab. One patient transplanted for Budd-Chiari syndrome who subsequently received adalimumab for UC was included. UC was diagnosed pre-transplant in all cases; pancolonic in 6 (75%). Mean age at OLT was 34.8 yrs (20.4–49.1) and all received tacrolimusbased immunosuppression. The median interval between OLT and initiation of anti-TNF was 3.1 (0.1–8.6) years.
Journal of Hepatology 2014 vol. 60 | S361–S522
Female gender Non-Caucasian METAVIR stage F3–4 Recipient IL28b CT/TT Genotype 1a Prior PR failure HCV RNA >800,000 IU/mL BOC (vs. TVR)
S366
Univariate analysis
Multivariate analysis
OR (95% CI)
P value
OR (95% CI)
P value
2.0 (0.8–5.0) 1.5 (0.5–4.4) 1.5 (0.6–3.5) 0.5 (0.1–2.1) 2.0 (0.8–5.2) 2.5 (0.6–10.3) 1.6 (0.5–5.5) 4.0 (1.5–10.6)
0.2 0.6 0.5 0.5 0.2 0.3 0.6 <0.01
3.1 (1.1–8.8)
0.03 NS NS NS NS NS NS 0.02
3.6 (1.2–10.9)
Conclusions: Our multicenter experience found higher SVR12 rates in TVR- compared with BOC-based treatment, partly because of fewer premature treatment discontinuations with TVR. P879 CIRCULATING miRNA-122/let-7d RATIO, HEPATITIS C VIRUS LOAD AND FIBROSING CHOLESTATIC HCV RECURRENCE AFTER LIVER TRANSPLANTATION A. Finkenstedt1 , S. Lechner1 , N. Baumgartner1 , J. Pratschke2 , I. Graziadei3 , W. Vogel1 , H. Zoller1 . 1 Department of Medicine II – Gastroenterology and Hepatology, 2 Department of Transplant Surgery, Medical University of Innsbruck, Innsbruck, 3 Department of Internal Medicine, Academic Teaching Hospital Hall in Tirol, Hall i. T., Austria E-mail: armin.fi[email protected] Background and Aims: Micro RNA 122 (miRNA-122) accounts for 70% of all hepatocellular micro RNA sequences and is essential for the replication of HCV. The aim of the study was to assess if miRNA122 concentrations two weeks after liver transplantation (LT) are predictive for fibrosing cholestatic HCV recurrence (FCH). Methods: The accuracy of serum miRNA-122 quantification critically depends on proper normalization with a stably expressed endogenous control. We therefore normalized the results with the best available internal normalizer let-7d. Micro RNA was extracted from serum samples using the Qiagen mirNeasy mini kit and miRNA-122 and let-7d were quantified by reverse transcription quantitative real-time PCR using TaqMan assays. Results: The study included 84 patients (68 men, mean age 55 years) who underwent LT for chronic HCV. In accordance with previous studies, let-7d normalized miRNA-122 was positively correlated with AST (r = 0.435; p < 0.001), ALT (r = 0.408; p < 0.001), gamma GT (r = 0.486; p < 0.001) and LDH (r = 0.481; p < 0.001). In contrast, miRNA-122 was not correlated with hepatitis C viral load at week 2. During follow-up, 12 patients developed fibrosing cholestatic HCV recurrence. miRNA-122 serum concentrations at week 2 after LT did not differ between patients with and without cholestatic recurrence. Conclusions: Normalized circulating miRNA-122 is not predictive for fibrosing cholestatic HCV recurrence. The moderate correlation of serum transaminase activities and miRNA-122 probably reflects the place of serum miRNA-122 in clinical hepatology: a sophisticated marker of hepatocellular integrity. P880 TERTIARY CENTRE EXPERIENCE OF THE SAFETY AND EFFICACY OF ANTI-TNFS FOR ULCERATIVE COLITIS (UC) AFTER LIVER TRANSPLANTATION A. Barnabas1 , J. Potts2 , K. Agarwal3 , B. Hayee2 . 1 King’s College Hospital, 2 Dept of Gastroenterology, 3 Institute for Liver Studies, King’s College Hospital, London, United Kingdom E-mail: [email protected] Background and Aims: Most patients with primary sclerosing cholangitis (PSC) have UC, which is usually mild in advanced PSC. However colitis may paradoxically worsen in up to 50% of patients following orthotopic liver transplantation (OLT), necessitating immunomodulator therapy. We reviewed our unit’s experience with anti-TNF agents post-OLT. Methods: A retrospective casenote review was performed of patients treated with anti-TNF agents post-OLT for colitis. Results: Eight patients (2 F) were identified; six with PSC-UC and one with autoimmune sclerosing cholangitis and UC received infliximab. One patient transplanted for Budd-Chiari syndrome who subsequently received adalimumab for UC was included. UC was diagnosed pre-transplant in all cases; pancolonic in 6 (75%). Mean age at OLT was 34.8 yrs (20.4–49.1) and all received tacrolimusbased immunosuppression. The median interval between OLT and initiation of anti-TNF was 3.1 (0.1–8.6) years.
Journal of Hepatology 2014 vol. 60 | S361–S522