- Email: [email protected]
T-09 Correlation between NS5A variants and fibrosis progression in patients with HCV recurrence after liver transplantation
Abstracts of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48 (baseline, 2–4–7–14–21–28 and 84 days after therapy) were analysed for HCV-RNA (Cobas Taqman, Roche) and HCV Core Ag assay (Architect, Abbott) to study the correlation between the two assays and their performance for SVR prediction. Results: Overall SVR was obtained in 29 of 57 pts treated with standard of care (SOC), 16 had rapid virologic response (RVR). Figure 1 shows HCVRNA and HCV Core Ag kinetics (mean values) in 39 SOC treated HCV-G1 patients. Table 1 reports the diagnostic performances of HCV-RNA (RVR) and undetectable (UND) HCV Core Ag at 7, 14, 21 and 28 days during therapy in P/R treated patients. Table 1 HCV-RNA RVR Core-7 UND Core-14 UND Core-21 UND Core-28 UND Sensitivity Specificity VPP VPN AD
55.2% 100.0% 100.0% 68.3% 77.2%
24.1% 100.0% 100.0% 56.0% 61.4%
51.7% 100.0% 100.0% 65.9% 75.0%
72.4% 96.3% 95.5% 76.5% 83.9%
82.8% 92.9% 92.3% 83.9% 87.7%
Conclusions: Early kinetics of serum HCV Core Ag during SOC therapy correlate with HCV-RNA kinetics. HCV Core Ag quantification appears a sensitive, specific and reliable new tool for management of CHC pts undergoing antiviral therapy.
T-07 rs4374383 polymorphism of MERTK gene influences the progression of liver fibrosis in thalassemia major patients with chronic hepatitis C V. Calvaruso, F. Bronte, S. Grimaudo, A. Di Cristina, V. Di Marco, on behalf of Sicilian Group for the Study of Hepatitis C in Thalassemia Gastroenterology Unit, Di.Bi.M.I.S., University of Palermo, Palermo Background and aim: Genome-wide association (GWA) studies identified a single nucleotide polymorphism (SNP), located in chromosome 2, associated with the liver fibrosis progression related to HCV infection. We studied the rs4374383 SNP of the MERTK gene, in a large, ethnically homogeneous cohort of transfused thalassemia major (TM) patients with a liver biopsy during the follow-up. Methods: We evaluated 211 TM patients (median age: 19.0, IQR: 13.0–28.0 years, 51.4% men) underwent liver biopsy between 1993 and 2010. Eighty patients (37.9%) were HCV-RNA negative and 131 (62.1%) had a chronic HCV infection (104 genotype 1or 4 and 27 genotype 2 or 3) acquired during the first 3 year of the life by blood transfusion. Logistic regression analysis was performed to evaluated the correlation between demographic features (gender and age at time of liver biopsy) alleles (AA vs. AG/GG) of rs4374383 SNP, viral genotype (1/4 vs. 2/3), histological features (grading of liver inflammation and liver iron concentration) and staging of liver fibrosis evaluated by Scheuer’s score. Results: In patients without HCV infection, age (OR: 1.08; 95% CI: 1.01– 1.15; p=0.032) and histological grading (OR: 11.73; 95% CI: 2.03–67.73; p=0.006) were independently associated with severe fibrosis (F3–F4). No significant differences regarding gender, liver iron concentration (LIC), ALT values and rs4374383 alleles of MERTK gene between patients with and without severe liver fibrosis have been found. Among patients with chronic HCV infection, age (OR: 1.05; 95% CI: 1.01– 1.10; p=0.023), HCV genotype 1/4 (OR: 3.73; 95% CI: 1.22–11.44; p=0.021), AG/GG alleles of rs4374383 SNP (OR: 4.16; 95% CI: 1.08–15.97; p=0.038) and grading A2-A4 of liver inflammation (OR: 3.35; 95% CI: 1.39–8.06; p=0.007) were independently associated with F3–F4 liver fibrosis by logistic regression analysis. Gender, LIC and ALT values were not related with severe fibrosis also in this group. Conclusion: Our study confirms that the genetic variations in MERTK gene and the duration of infection effect the progression of liver fibrosis in TM patients with chronic HCV hepatitis.
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T-08 Interplay between on-treatment predictors and donor/recipients IL28B in predicting SVR to pegIFN/ribavirin in HCV-1,4 liver transplant recipients M.F. Donato 1 , C. Rigamonti 1 , J. Bastiampillai 1 , A. Aghemo 1 , E. Galmozzi 1 , T. De Feo 2 , E. Longhi 2 , G. Rossi 3 , M. Colombo 1 1 1st Division of Gastroenterology, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 2 North Italy Transplant Program, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 3 Liver Transplant Unit, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
Background and aim: PR therapy of recurrent HCV after liver transplantation (LT) improves graft and patient survival. The clinical benefits of donor/recipients (D/R) features which have been identified to predict SVR is disputed. Methods: Since 2000, 54 consecutive LT recipients with progressive hepatitis C due to HCV 1–4 on protocol liver biopsy (Ishak grading≥8 and/or staging≥2) received a GFR-based dose of PR intended for 48 weeks. IL28B genotype was tested in D/R PBMC by standard methods. The PR dose was adjusted on patient tolerability/side effects. Results: Overall, 48/54 patients received PR at least 24 weeks and completed the post-treatment follow-up whereas 6 discontinued therapy. Males were 81%, 43% with HCC, median R-age=54 yr and D-age=56 yr; R-IL28B CC=29%, CT=50%, TT=21%; D-IL28B CC=54%, CT=33%, TT=13%; Immunosuppression was cyclosporine in 69% and tacrolimus 31%. PR was started 19 months from LT and given for 52 weeks in median. At baseline, median ALT were 81 IU/l, HCV-RNA 6.3 log10 , 8% cirrhosis, 6% cholestatic hepatitis. Outcomes were: SVR in 21 (39% by ITT, 44% PP), rapid virological response (RVR) in 6 (13%), complete early virological response (cEVR) in 21 (44%), relapse in 13 (27%). SVR was significantly higher in RVR (100% vs. 37%, p=0.004) and in cEVR (76% vs. 18%, p=0.0001) but was similar in recipients with D-IL28B vs. CT/TT (p=0.77), R-IL28B CC vs. CT/TT (p=0.33), D/R-IL28B CC vs. CT/TT (p=0.23), in those with older vs. younger graft (p=0.37) and with cyclosporine vs. tacrolimus immunosuppression (p=0.36). After splitting recipients according to RVR and cEVR (yes vs. no) D/R-IL28B status (CC vs. CT/TT) did not emerge as a predictor of SVR. Conclusions: D/R-IL28B status did not predict the outcome of PR in HCV-1,4 LT recipients, which was independently predicted by EVR, only.
T-09 Correlation between NS5A variants and fibrosis progression in patients with HCV recurrence after liver transplantation I. Lenci 1 , S. Cucchiarelli 1 , V.C. Di Maio 2 , V. Cento 2 , F. De Luca 2 , M. Milana 1 , F.P. Antonucci 2 , D. Di Paolo 1 , E. Giardina 3 , G. Tisone 4 , M. Angelico 1 , C.F. Perno 2 , F. Ceccherini Silberstein 2 1 Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Rome, Italy; 2 Chair of Virology, Tor Vergata University, Rome, Italy; 3 Department of Biopathology, Tor Vergata University, Rome, Italy; 4 Liver Transplant Center, Tor Vergata University, Rome, Italy
Introduction: Recurrence of HCV-disease after liver transplantation (LT) impairs patient survival, with up to 30% of recurrent HCV-infections progressing to cirrhosis within 5 years. We evaluated the role of host and viral factors in determining faster disease progression in patients with HCV-recurrence. Methods: Nineteen patients (57.9% males, median (IQR) age: 65 (60–69) years, transplanted between 1995 and 2009, with histology proven for HCVrecurrence and failure of peg-interferon+ribavirin treatment performed after LT, were studied. Patients were classified as slow-fibrosis or fast-fibrosis progressors according to histological staging at year 1 after LT (cut-off: ≥1 points of Ishak-score). NS3-protease (181 amino-acids) and full length NS5A and core sequences were obtained by population-sequencing. Detected mutations were correlated with fibrosis progression by the Fisher exact-test. Results: Eight patients were classified as slow-fibrosis progressors (42.1%; 1a=1; 1b=7, 37.5% IL28B-CC) and eleven as fast-fibrosis progressors (57.9%; 1a=4; 1b=7, 27.2% IL28B-TT). This classification was confirmed also at year
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Abstracts of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48
3 after LT (cut-off: ≥3 points of Ishak-score). NS3, NS5A and core sequences were obtained in 16 (100%), 18 (94.7%) and 17 (89.5%) patients, respectively. One NS5A-mutation (D402N), located in the V3-domain of the interferonresistance-determining region (IRRDR), was significantly correlated with a slower fibrosis progression of HCV-related disease after LT, being detected in 1/11 (9%) fast-progressor and in 4/7 (57.1%) slow-progressors, respectively (p=0.047). No other mutations in either NS3, NS5A or core proteins were significantly associated with fibrosis progression. The already-described M91L core mutation showed a trend of association with faster fibrosis-progression, since it was found in 3/10 (30%) fast-progressors and 0/7 slow-progressors (p=0.22). Conclusions: These results suggest that a novel mutation of NS5A protein is associated with slower progression of HCV-recurrence in LT-recipients and a trend was found for a core mutation previously associated with HCVpathogenesis. These data could be relevant to manage the recurrent HCV disease, although need to be confirmed in larger studies.
T-10 Acute exacerbation of chronic hepatitis C: clinical presentation, outcome and response to anti-HCV treatment E. Sagnelli 1,2 , M. Pisaturo 1,2 , M. Stanzione 3 , V. Messina 2 , C. Sagnelli 3 , L. Alessio 1 , M. Starace 1 , G. Pasquale 1 , N. Coppola 1 1 Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy; 2 Division of Infectious and Tropical Diseases, AORN Sant’Anna e San Sebastiano di Caserta, Caserta, Italy; 3 Department of Clinical and Experimental Medicine and Surgery “F. Magrassi e A. Lanzara”, Second University of Naples, Naples, Italy
Aim: To improve the knowledge on acute exacerbation of chronic hepatitis C (ae-CHC). Methods: We prospectively investigated 82 consecutive, symptomatic aeCHC patients (Cases) and 82 subjects without reactivation over a decade (Controls), pair matched by age, sex and HCV genotype. The patients in the Case group had a mean age of 53 years (23–87), males predominated (76%) and the most frequent HCV genotypes were genotype 2 (46.4%) and genotype 1 (43.9%); the patients in the Control group showed the same characteristics, reflecting their selection criteria. Results: In the Cases ALT was 1,063±1,038 IU/dL and total bilirubin 15.87±7.15 mg/dL. IL-28B CC genotype was more frequent in the Cases than the Controls (40.2% vs. 24.4%; p<0.05). Sixty-nine Cases and 73 Controls were followed up for at least 2 years. In the Cases, 43.5% of patients showed a steady ALT increase ≥2-fold baseline values and 56.5% returned to their values before ae-CHC. Twenty-three Cases and 31 Controls, all naïve to antiHCV therapy, had two liver biopsies, one before enrolment and one during the follow up [at a 5.85- (IQR 4.2–7.1) and 5.05- (IQR 4.18–6.89) year interval, respectively]. In these patients, deterioration in liver fibrosis ≥2 scores (Ishak) was observed in 18 (78.3%) Cases and in 11 (35.5%) Controls (p<0.005); deterioration in necroinflammation ≥2 scores occurred in 14 (60.9%) Cases and 3 (9.6%) Controls (p<0.005). Thirty-two (46.4%) Cases and 38 (52%) Controls received pegylated interferon plus ribavirin and a sustained viral response was achieved in 26 (81.2%) Cases and 23 (60.5%) Controls. Conclusion: ae-CHC is a clinical event frequently responsible for an unfavourable outcome; however, a clear tendency to achieve a SVR to antiviral therapy was observed.
L. Pasulo 17 , S. Fagiuoli 17 , A.E. Colombo 18 , G. Bellati 18 , M. Milanese 19 , M. Strazzabosco 19 , M. Pozzi 20 , N.M. Terreni 21 , G. Spinzi 21 , M. Quagliuolo 22 , M. Borzio 22 , G. Lunghi 23 , F. Facchetti 1 , F. Invernizzi 1 , M. Colombo 1 1 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano; 2 UO Epatologia, Ospedale San Giuseppe,Università degli Studi di Milano, Milan; 3 Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni; 4 Infectious Diseases, Ospedali Riuniti di Bergamo, Bergamo; 5 II Divisione Malattie Infettive, Azienda Ospedaliera Spedali Civili, Brescia; 6 I and II Division Infectious Diseases, Ospedale Luigi Sacco, Milan; 7 INMI, IRCCS L. Spallanzani, Roma; 8 SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda; 9 Internal Medicine 1b, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan; 10 UO Epatologia, Ospedale di Treviglio, Treviglio; 11 UO Gastroenterologia, Policlinico S. Marco, Zingonia; 12 UO Epatologia, Azienda Ospedaliero-Universitaria Pisana, Pisa; 13 SC Medicina Generale, Ospedale A. Manzoni, Lecco; 14 Clinic of Infectious Diseases, Università di Bari, Bari; 15 Clinic of Infectious Diseases, Università di Foggia, Foggia; 16 Division of Medicine, Policlinico San Pietro, Ponte San Pietro; 17 Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo; 18 Unità Operativa di Medicina, Servizio di Epatologia, Ospedale Sant’Anna, Como; 19 Liver Center, Gastroenterologia, Azienda Ospedaliera San Gerardo, Università Milano Bicocca, Monza; 20 UO Medicina, Ospedale Fatebenefratelli, Erba; 21 UO Gastroenterologia, Ospedale Valduce, Como; 22 UO Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano; 23 Istituto di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
We assessed the 5-year effectiveness and safety of Entecavir (ETV) monotherapy in NUC-naïve patients and the risk of HCC in compensated cirrhotics. Methods: 418 consecutive NUC-naïve patients with CHB recruited in 22 Liver Units in Italy were treated with ETV 0.5 mg for 52 months (range 2–66 months). At baseline, age was 58 years, 76% males, 83% HBeAg-negative, HBV-DNA 6.0 log IU/ml, 85% with elevated ALT, 49% cirrhotics, 56% with concomitant diseases/medications. Liver function tests and HBV-DNA were assessed every 3–4 months. Results: Undetectable HBV-DNA rates progressively increased over time reaching 100% in both HBeAg-positive and negative-patients at year 5. 1% of patients had a primary non-response, 12% a partial response at week-48, 11% a blip of viremia, 4% a virological breakthrough and <1% developed ETV resistance. HBeAg seroconversion and HBsAg loss progressively increased up to 52% and 33% at year 5, respectively, with 13 patients withdrawing successfully from therapy. ALT levels became normal in 93% of patients. Serum creatinine and blood phosphorus remained unchanged during treatment as well as the proportion of patients with serum creatinine >1.5 mg/dl. TmPO4/GFR ratio was <0.80 mmol/L in ∼30% at month 12 and throughout the study. No safety issues were reported. HCC developed in 5 non cirrhotics (2.4%) between month 19 and 46 of treatment, with a yearly rate of 0.5%. The 155 compensated cirrhotics remained clinically stable, yet 17 developed a HCC to give a 5-year cumulative rate of 14% and a yearly rate of 2.8%, despite full suppression of viral replication in most cases. Five cirrhotics died for non-liver related causes, 2 for HCC and 4 were transplanted for HCC: the overall 5-year cumulative survival and liver-related survival were 91% and 95%, respectively. Conclusion: Entecavir monotherapy efficiently suppressed HBV in naïve patients with CHB, fully preventing clinical decompensation but not HCC.
T-12 T-11 5-year entecavir in NUC-naïve, field-practice patients with CHB showed excellent viral suppression and safety but no prevention of HCC
Tenofovir suppressed viral suppression in most field practice, treatment-naïve patients with CHB followed for 3 years in a multicenter European study
P. Lampertico 1 , R. Soffredini 1 , M. Viganò 2 , E. Minola 3 , G. Cologni 4 , M. Rizzi 4 , S. Zaltron 5 , A. Vavassori 5 , F. Castelli 5 , E. Angeli 6 , G.A. Gubertini 6 , C. Magni 6 , G. Rizzardini 6 , A. Testa 7 , G. D’Offizi 7 , M. Vinci 8 , G. Pinzello 8 , E. Fatta 9 , S. Fargion 9 , S. Colombo 10 , O. Fracassetti 10 , P. Del Poggio 11 , B. Coco 12 , M.R. Brunetto 12 , M. Andreoletti 13 , A. Colli 13 , M. Fasano 14 , T. Santantonio 15 , G. Colloredo 16 ,
P. Lampertico 1 , R. Soffredini 1 , M. Viganò 2 , C. Yurdaydin 3 , R. Idilman 3 , G.V. Papatheodoridis 4 , E. Margariti 4 , M. Buti 5 , R. Esteban 5 , S. Zaltron 6 , A. Vavassori 6 , G. Carosi 6 , E. Minola 7 , M. Vinci 8 , G. Pinzello 8 , A.M. Giorgini 9 , M. Zuin 9 , A. Salmi 10 , S. Colombo 11 , O. Fracassetti 11 , P. Del Poggio 12 , S. Bruno 13 , L. Pasulo 14 , S. Fagiuoli 14 , M. Andreoletti 15 , A. Colli 15 , F. Fumagalli Maldini 16 , M. Milanese 16 , M. Strazzabosco 16 ,
55.2% 100.0% 100.0% 68.3% 77.2%
24.1% 100.0% 100.0% 56.0% 61.4%
51.7% 100.0% 100.0% 65.9% 75.0%
72.4% 96.3% 95.5% 76.5% 83.9%
82.8% 92.9% 92.3% 83.9% 87.7%
Conclusions: Early kinetics of serum HCV Core Ag during SOC therapy correlate with HCV-RNA kinetics. HCV Core Ag quantification appears a sensitive, specific and reliable new tool for management of CHC pts undergoing antiviral therapy.
T-07 rs4374383 polymorphism of MERTK gene influences the progression of liver fibrosis in thalassemia major patients with chronic hepatitis C V. Calvaruso, F. Bronte, S. Grimaudo, A. Di Cristina, V. Di Marco, on behalf of Sicilian Group for the Study of Hepatitis C in Thalassemia Gastroenterology Unit, Di.Bi.M.I.S., University of Palermo, Palermo Background and aim: Genome-wide association (GWA) studies identified a single nucleotide polymorphism (SNP), located in chromosome 2, associated with the liver fibrosis progression related to HCV infection. We studied the rs4374383 SNP of the MERTK gene, in a large, ethnically homogeneous cohort of transfused thalassemia major (TM) patients with a liver biopsy during the follow-up. Methods: We evaluated 211 TM patients (median age: 19.0, IQR: 13.0–28.0 years, 51.4% men) underwent liver biopsy between 1993 and 2010. Eighty patients (37.9%) were HCV-RNA negative and 131 (62.1%) had a chronic HCV infection (104 genotype 1or 4 and 27 genotype 2 or 3) acquired during the first 3 year of the life by blood transfusion. Logistic regression analysis was performed to evaluated the correlation between demographic features (gender and age at time of liver biopsy) alleles (AA vs. AG/GG) of rs4374383 SNP, viral genotype (1/4 vs. 2/3), histological features (grading of liver inflammation and liver iron concentration) and staging of liver fibrosis evaluated by Scheuer’s score. Results: In patients without HCV infection, age (OR: 1.08; 95% CI: 1.01– 1.15; p=0.032) and histological grading (OR: 11.73; 95% CI: 2.03–67.73; p=0.006) were independently associated with severe fibrosis (F3–F4). No significant differences regarding gender, liver iron concentration (LIC), ALT values and rs4374383 alleles of MERTK gene between patients with and without severe liver fibrosis have been found. Among patients with chronic HCV infection, age (OR: 1.05; 95% CI: 1.01– 1.10; p=0.023), HCV genotype 1/4 (OR: 3.73; 95% CI: 1.22–11.44; p=0.021), AG/GG alleles of rs4374383 SNP (OR: 4.16; 95% CI: 1.08–15.97; p=0.038) and grading A2-A4 of liver inflammation (OR: 3.35; 95% CI: 1.39–8.06; p=0.007) were independently associated with F3–F4 liver fibrosis by logistic regression analysis. Gender, LIC and ALT values were not related with severe fibrosis also in this group. Conclusion: Our study confirms that the genetic variations in MERTK gene and the duration of infection effect the progression of liver fibrosis in TM patients with chronic HCV hepatitis.
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T-08 Interplay between on-treatment predictors and donor/recipients IL28B in predicting SVR to pegIFN/ribavirin in HCV-1,4 liver transplant recipients M.F. Donato 1 , C. Rigamonti 1 , J. Bastiampillai 1 , A. Aghemo 1 , E. Galmozzi 1 , T. De Feo 2 , E. Longhi 2 , G. Rossi 3 , M. Colombo 1 1 1st Division of Gastroenterology, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 2 North Italy Transplant Program, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 3 Liver Transplant Unit, IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
Background and aim: PR therapy of recurrent HCV after liver transplantation (LT) improves graft and patient survival. The clinical benefits of donor/recipients (D/R) features which have been identified to predict SVR is disputed. Methods: Since 2000, 54 consecutive LT recipients with progressive hepatitis C due to HCV 1–4 on protocol liver biopsy (Ishak grading≥8 and/or staging≥2) received a GFR-based dose of PR intended for 48 weeks. IL28B genotype was tested in D/R PBMC by standard methods. The PR dose was adjusted on patient tolerability/side effects. Results: Overall, 48/54 patients received PR at least 24 weeks and completed the post-treatment follow-up whereas 6 discontinued therapy. Males were 81%, 43% with HCC, median R-age=54 yr and D-age=56 yr; R-IL28B CC=29%, CT=50%, TT=21%; D-IL28B CC=54%, CT=33%, TT=13%; Immunosuppression was cyclosporine in 69% and tacrolimus 31%. PR was started 19 months from LT and given for 52 weeks in median. At baseline, median ALT were 81 IU/l, HCV-RNA 6.3 log10 , 8% cirrhosis, 6% cholestatic hepatitis. Outcomes were: SVR in 21 (39% by ITT, 44% PP), rapid virological response (RVR) in 6 (13%), complete early virological response (cEVR) in 21 (44%), relapse in 13 (27%). SVR was significantly higher in RVR (100% vs. 37%, p=0.004) and in cEVR (76% vs. 18%, p=0.0001) but was similar in recipients with D-IL28B vs. CT/TT (p=0.77), R-IL28B CC vs. CT/TT (p=0.33), D/R-IL28B CC vs. CT/TT (p=0.23), in those with older vs. younger graft (p=0.37) and with cyclosporine vs. tacrolimus immunosuppression (p=0.36). After splitting recipients according to RVR and cEVR (yes vs. no) D/R-IL28B status (CC vs. CT/TT) did not emerge as a predictor of SVR. Conclusions: D/R-IL28B status did not predict the outcome of PR in HCV-1,4 LT recipients, which was independently predicted by EVR, only.
T-09 Correlation between NS5A variants and fibrosis progression in patients with HCV recurrence after liver transplantation I. Lenci 1 , S. Cucchiarelli 1 , V.C. Di Maio 2 , V. Cento 2 , F. De Luca 2 , M. Milana 1 , F.P. Antonucci 2 , D. Di Paolo 1 , E. Giardina 3 , G. Tisone 4 , M. Angelico 1 , C.F. Perno 2 , F. Ceccherini Silberstein 2 1 Hepatology Unit, Department of Internal Medicine, Tor Vergata University, Rome, Italy; 2 Chair of Virology, Tor Vergata University, Rome, Italy; 3 Department of Biopathology, Tor Vergata University, Rome, Italy; 4 Liver Transplant Center, Tor Vergata University, Rome, Italy
Introduction: Recurrence of HCV-disease after liver transplantation (LT) impairs patient survival, with up to 30% of recurrent HCV-infections progressing to cirrhosis within 5 years. We evaluated the role of host and viral factors in determining faster disease progression in patients with HCV-recurrence. Methods: Nineteen patients (57.9% males, median (IQR) age: 65 (60–69) years, transplanted between 1995 and 2009, with histology proven for HCVrecurrence and failure of peg-interferon+ribavirin treatment performed after LT, were studied. Patients were classified as slow-fibrosis or fast-fibrosis progressors according to histological staging at year 1 after LT (cut-off: ≥1 points of Ishak-score). NS3-protease (181 amino-acids) and full length NS5A and core sequences were obtained by population-sequencing. Detected mutations were correlated with fibrosis progression by the Fisher exact-test. Results: Eight patients were classified as slow-fibrosis progressors (42.1%; 1a=1; 1b=7, 37.5% IL28B-CC) and eleven as fast-fibrosis progressors (57.9%; 1a=4; 1b=7, 27.2% IL28B-TT). This classification was confirmed also at year
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Abstracts of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48
3 after LT (cut-off: ≥3 points of Ishak-score). NS3, NS5A and core sequences were obtained in 16 (100%), 18 (94.7%) and 17 (89.5%) patients, respectively. One NS5A-mutation (D402N), located in the V3-domain of the interferonresistance-determining region (IRRDR), was significantly correlated with a slower fibrosis progression of HCV-related disease after LT, being detected in 1/11 (9%) fast-progressor and in 4/7 (57.1%) slow-progressors, respectively (p=0.047). No other mutations in either NS3, NS5A or core proteins were significantly associated with fibrosis progression. The already-described M91L core mutation showed a trend of association with faster fibrosis-progression, since it was found in 3/10 (30%) fast-progressors and 0/7 slow-progressors (p=0.22). Conclusions: These results suggest that a novel mutation of NS5A protein is associated with slower progression of HCV-recurrence in LT-recipients and a trend was found for a core mutation previously associated with HCVpathogenesis. These data could be relevant to manage the recurrent HCV disease, although need to be confirmed in larger studies.
T-10 Acute exacerbation of chronic hepatitis C: clinical presentation, outcome and response to anti-HCV treatment E. Sagnelli 1,2 , M. Pisaturo 1,2 , M. Stanzione 3 , V. Messina 2 , C. Sagnelli 3 , L. Alessio 1 , M. Starace 1 , G. Pasquale 1 , N. Coppola 1 1 Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy; 2 Division of Infectious and Tropical Diseases, AORN Sant’Anna e San Sebastiano di Caserta, Caserta, Italy; 3 Department of Clinical and Experimental Medicine and Surgery “F. Magrassi e A. Lanzara”, Second University of Naples, Naples, Italy
Aim: To improve the knowledge on acute exacerbation of chronic hepatitis C (ae-CHC). Methods: We prospectively investigated 82 consecutive, symptomatic aeCHC patients (Cases) and 82 subjects without reactivation over a decade (Controls), pair matched by age, sex and HCV genotype. The patients in the Case group had a mean age of 53 years (23–87), males predominated (76%) and the most frequent HCV genotypes were genotype 2 (46.4%) and genotype 1 (43.9%); the patients in the Control group showed the same characteristics, reflecting their selection criteria. Results: In the Cases ALT was 1,063±1,038 IU/dL and total bilirubin 15.87±7.15 mg/dL. IL-28B CC genotype was more frequent in the Cases than the Controls (40.2% vs. 24.4%; p<0.05). Sixty-nine Cases and 73 Controls were followed up for at least 2 years. In the Cases, 43.5% of patients showed a steady ALT increase ≥2-fold baseline values and 56.5% returned to their values before ae-CHC. Twenty-three Cases and 31 Controls, all naïve to antiHCV therapy, had two liver biopsies, one before enrolment and one during the follow up [at a 5.85- (IQR 4.2–7.1) and 5.05- (IQR 4.18–6.89) year interval, respectively]. In these patients, deterioration in liver fibrosis ≥2 scores (Ishak) was observed in 18 (78.3%) Cases and in 11 (35.5%) Controls (p<0.005); deterioration in necroinflammation ≥2 scores occurred in 14 (60.9%) Cases and 3 (9.6%) Controls (p<0.005). Thirty-two (46.4%) Cases and 38 (52%) Controls received pegylated interferon plus ribavirin and a sustained viral response was achieved in 26 (81.2%) Cases and 23 (60.5%) Controls. Conclusion: ae-CHC is a clinical event frequently responsible for an unfavourable outcome; however, a clear tendency to achieve a SVR to antiviral therapy was observed.
L. Pasulo 17 , S. Fagiuoli 17 , A.E. Colombo 18 , G. Bellati 18 , M. Milanese 19 , M. Strazzabosco 19 , M. Pozzi 20 , N.M. Terreni 21 , G. Spinzi 21 , M. Quagliuolo 22 , M. Borzio 22 , G. Lunghi 23 , F. Facchetti 1 , F. Invernizzi 1 , M. Colombo 1 1 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano; 2 UO Epatologia, Ospedale San Giuseppe,Università degli Studi di Milano, Milan; 3 Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni; 4 Infectious Diseases, Ospedali Riuniti di Bergamo, Bergamo; 5 II Divisione Malattie Infettive, Azienda Ospedaliera Spedali Civili, Brescia; 6 I and II Division Infectious Diseases, Ospedale Luigi Sacco, Milan; 7 INMI, IRCCS L. Spallanzani, Roma; 8 SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda; 9 Internal Medicine 1b, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan; 10 UO Epatologia, Ospedale di Treviglio, Treviglio; 11 UO Gastroenterologia, Policlinico S. Marco, Zingonia; 12 UO Epatologia, Azienda Ospedaliero-Universitaria Pisana, Pisa; 13 SC Medicina Generale, Ospedale A. Manzoni, Lecco; 14 Clinic of Infectious Diseases, Università di Bari, Bari; 15 Clinic of Infectious Diseases, Università di Foggia, Foggia; 16 Division of Medicine, Policlinico San Pietro, Ponte San Pietro; 17 Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo; 18 Unità Operativa di Medicina, Servizio di Epatologia, Ospedale Sant’Anna, Como; 19 Liver Center, Gastroenterologia, Azienda Ospedaliera San Gerardo, Università Milano Bicocca, Monza; 20 UO Medicina, Ospedale Fatebenefratelli, Erba; 21 UO Gastroenterologia, Ospedale Valduce, Como; 22 UO Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano; 23 Istituto di Medicina Preventiva, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
We assessed the 5-year effectiveness and safety of Entecavir (ETV) monotherapy in NUC-naïve patients and the risk of HCC in compensated cirrhotics. Methods: 418 consecutive NUC-naïve patients with CHB recruited in 22 Liver Units in Italy were treated with ETV 0.5 mg for 52 months (range 2–66 months). At baseline, age was 58 years, 76% males, 83% HBeAg-negative, HBV-DNA 6.0 log IU/ml, 85% with elevated ALT, 49% cirrhotics, 56% with concomitant diseases/medications. Liver function tests and HBV-DNA were assessed every 3–4 months. Results: Undetectable HBV-DNA rates progressively increased over time reaching 100% in both HBeAg-positive and negative-patients at year 5. 1% of patients had a primary non-response, 12% a partial response at week-48, 11% a blip of viremia, 4% a virological breakthrough and <1% developed ETV resistance. HBeAg seroconversion and HBsAg loss progressively increased up to 52% and 33% at year 5, respectively, with 13 patients withdrawing successfully from therapy. ALT levels became normal in 93% of patients. Serum creatinine and blood phosphorus remained unchanged during treatment as well as the proportion of patients with serum creatinine >1.5 mg/dl. TmPO4/GFR ratio was <0.80 mmol/L in ∼30% at month 12 and throughout the study. No safety issues were reported. HCC developed in 5 non cirrhotics (2.4%) between month 19 and 46 of treatment, with a yearly rate of 0.5%. The 155 compensated cirrhotics remained clinically stable, yet 17 developed a HCC to give a 5-year cumulative rate of 14% and a yearly rate of 2.8%, despite full suppression of viral replication in most cases. Five cirrhotics died for non-liver related causes, 2 for HCC and 4 were transplanted for HCC: the overall 5-year cumulative survival and liver-related survival were 91% and 95%, respectively. Conclusion: Entecavir monotherapy efficiently suppressed HBV in naïve patients with CHB, fully preventing clinical decompensation but not HCC.
T-12 T-11 5-year entecavir in NUC-naïve, field-practice patients with CHB showed excellent viral suppression and safety but no prevention of HCC
Tenofovir suppressed viral suppression in most field practice, treatment-naïve patients with CHB followed for 3 years in a multicenter European study
P. Lampertico 1 , R. Soffredini 1 , M. Viganò 2 , E. Minola 3 , G. Cologni 4 , M. Rizzi 4 , S. Zaltron 5 , A. Vavassori 5 , F. Castelli 5 , E. Angeli 6 , G.A. Gubertini 6 , C. Magni 6 , G. Rizzardini 6 , A. Testa 7 , G. D’Offizi 7 , M. Vinci 8 , G. Pinzello 8 , E. Fatta 9 , S. Fargion 9 , S. Colombo 10 , O. Fracassetti 10 , P. Del Poggio 11 , B. Coco 12 , M.R. Brunetto 12 , M. Andreoletti 13 , A. Colli 13 , M. Fasano 14 , T. Santantonio 15 , G. Colloredo 16 ,
P. Lampertico 1 , R. Soffredini 1 , M. Viganò 2 , C. Yurdaydin 3 , R. Idilman 3 , G.V. Papatheodoridis 4 , E. Margariti 4 , M. Buti 5 , R. Esteban 5 , S. Zaltron 6 , A. Vavassori 6 , G. Carosi 6 , E. Minola 7 , M. Vinci 8 , G. Pinzello 8 , A.M. Giorgini 9 , M. Zuin 9 , A. Salmi 10 , S. Colombo 11 , O. Fracassetti 11 , P. Del Poggio 12 , S. Bruno 13 , L. Pasulo 14 , S. Fagiuoli 14 , M. Andreoletti 15 , A. Colli 15 , F. Fumagalli Maldini 16 , M. Milanese 16 , M. Strazzabosco 16 ,