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Effectiveness of Adalibumab for patients with primary sclerosing cholangitis associated with inflammatory bowel disease
Abstracts / Digestive and Liver Disease 47S (2015) e19–e42
T-47 BOCEPREVIR OR TELAPREVIR PLUS PEGINTERFERON/RIBAVIRIN IN HCV CHRONIC INFECTION: THE REAL-LIFE EXPERIENCE OF THE ITALIAN ASSOCIATION OF HOSPITAL HEPATOLOGISTS (CLEO)
e41
the mean follow-up was 103.8 ± 86 months. Forty-nine patients (53.3%) had associated IBD (38 ulcerative colitis, 10 Crohn’s disease, 1 indeterminate colitis). Clinical activity and endoscopic severity were scored according to the CD activity index and Mayo subscore for endoscopy. Results: Table 1 shows the major events occurred during the follow-up:
CLEO DAAs Study Group, CLEO, Rome, Italy Introduction: Boceprevir/Telaprevir (DAAs), approved for reimbursement in Italy in December 2012, were used from January 2013. Since then the group of the Association of Hospital Hepatologists (CLEO DAAs Study Group) has been deeply involved in using DAAs. In September 2013, the Governing Board of the Association decided to collect data from Hospital Centers, where there were active members belonging to CLEO. For this reason, this study can be qualified as retrospective/prospective. Aim: to check safety and efficacy of this type of treatment in the real-world setting. Patients and Methods: A database was prepared and used by all Centres for the data collection and updated continuously. Last update: November 26, 2014. All patients consecutively treated were included; data were analyzed according to the intention-totreat principle. HCV-RNA was analyzed using: COBAS TaqMan 2.0 (Roche) with LLQ 25IU/mL. Results: 40 Centres enrolled 737 patients: male 64%; median age 58 (range 18-78), of whom 20.2% over 65; mean BMI 25.6 (range 16-39); Genotype 1b (78.4%); fibrosis F3/4 (70%). DAAs used: Telaprevir (67%); PEGIFN-2a (71%); patients naïve (28%), relapsers (32%), non-responders (40%). Therapy was stopped in 13.4% cases because of side-effects (anaemia 37%, rash 26%) or for virological failure (16.2%). Since the study is ongoing, we have 563 patients who completed the follow-up. The RVR was achieved in 68% cases, EOT in 64%, while the SVR was achieved in 68% in F0-F1; 57% in F2-F3 and 37% in F4. In cirrhotic aging > 65 the SVR was 34%. There were no fatalities. Conclusions: DAAs, in everyday practice, are safe but with moderate efficacy. These data confirm the limited success of DAAs in certain groups of patients such as those widely represented in our series: advanced fibrosis/cirrhosis, non-responders to PEGIFN/RIBA and the over 65s. As for the SVR, the grade of fibrosis makes the difference. http://dx.doi.org/10.1016/j.dld.2015.01.090 T-48 EFFECTIVENESS OF ADALIBUMAB FOR PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE I. Franceschet, N. Cazzagon, A. Floreani Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy Background: Primary sclerosing cholangitis (PSC) is a chronic biliary disease with a marked comorbidity with extra-hepatic conditions, mainly inflammatory bowel disease (IBD). The medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been able to demonstrate efficacy in IBD. Aim: To analyse: 1) the natural history of patients with PSC ± associated with IBD; 2) the long-term efficacy of biologics in patients with PSC and concomitant IBD. Methods: 92 consecutive PSC patients (seen from 1987 to 2014) were included in the study: 50 (54.3%) were males, and 42 (45.7%) females. The mean age at diagnosis was 32.0 ± 14.3 years, and
Events
PSC + IBD (N.49)
PSC-IBD (N.43)
p
OLTx CCA HCC Gallbladder cancer Colo-rectal cancer Death
7 (14.3%) 0 2 (4.1%) 1 (2.0%) 4 (8.2%) 5 (10.2%)
7 (16.3%) 2 (4.6%) 0 0 0 5 (11.6%)
0.79 0.13 0.18 0.35 0.05 0.83
Three patients with IBD experienced, as second-line treatment, Adalimumab (ADA), an anti-TNFa monoclonal antibody, previous written consensus. Patients were assessed before starting treatment, at month 6 and 12. ADA induction was 160 mg at week 0, and then 80 mg at week 2, while ADA maintenance treatment was 40 mg every 2 weeks. After 6 and 12 months of ADA, a sustained clinical remission of IBD was obtained; a reduction in ALT, GGT, alkaline phosphatase and Mayo PSC score was obtained. Conclusions: This is the first study evaluating the efficacy of biologic agents in PSC. Promising results come from ADA for PSC + IBD during a 12 months follow-up. Furthers studies are warranted to investigate the long-term tolerability and efficacy in such patients. http://dx.doi.org/10.1016/j.dld.2015.01.091 T-49 POSITIVE CORRELATION OF HIF2␣ AND SERPINB3 IN HUMAN HEPATOCELLULAR CARCINOMA: SELECTIVITY AND PROGNOSTIC IMPLICATIONS E. Morello 1 , C. Turato 2 , S. Cannito 1 , M. Ruvoletto 2 , S. Quarta 2 , C. Paternostro 1 , E. Novo 1 , R. Autelli 1 , S. Fasolato 2 , I. Tusa 3 , E. Rovida 3 , S. Colombatto 4 , A. Smedile 5 , A. Vitale 6 , G. Zanus 6 , U. Cillo 6 , M. Parola 1 , P. Pontisso 2 1 Department Clinical and Biological Sciences, Unit of Experimental Medicine, University of Turin, Turin, Italy 2 Department Medicine, University of Padua, Padua, Italy 3 Department Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy 4 Department Oncology and 5 Department Medical Sciences, University of Torino, Italy 6 Department Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
Background SerpinB3, a cysteine-proteases inhibitor upregulated in hepatocellular carcinoma (HCC), proposed as biomarker of liver carcinogenesis and to stimulate epithelial-tomesenchymal transition (EMT) and increased invasiveness in liver cancer cells, has been suggested to be up-regulated by hypoxia through a HIF2␣-dependent mechanism. Aims To investigate the selectivity of HIF2␣-related upregulation of SerpinB3 and the in vivo prognostic relevance of this relationships.
T-47 BOCEPREVIR OR TELAPREVIR PLUS PEGINTERFERON/RIBAVIRIN IN HCV CHRONIC INFECTION: THE REAL-LIFE EXPERIENCE OF THE ITALIAN ASSOCIATION OF HOSPITAL HEPATOLOGISTS (CLEO)
e41
the mean follow-up was 103.8 ± 86 months. Forty-nine patients (53.3%) had associated IBD (38 ulcerative colitis, 10 Crohn’s disease, 1 indeterminate colitis). Clinical activity and endoscopic severity were scored according to the CD activity index and Mayo subscore for endoscopy. Results: Table 1 shows the major events occurred during the follow-up:
CLEO DAAs Study Group, CLEO, Rome, Italy Introduction: Boceprevir/Telaprevir (DAAs), approved for reimbursement in Italy in December 2012, were used from January 2013. Since then the group of the Association of Hospital Hepatologists (CLEO DAAs Study Group) has been deeply involved in using DAAs. In September 2013, the Governing Board of the Association decided to collect data from Hospital Centers, where there were active members belonging to CLEO. For this reason, this study can be qualified as retrospective/prospective. Aim: to check safety and efficacy of this type of treatment in the real-world setting. Patients and Methods: A database was prepared and used by all Centres for the data collection and updated continuously. Last update: November 26, 2014. All patients consecutively treated were included; data were analyzed according to the intention-totreat principle. HCV-RNA was analyzed using: COBAS TaqMan 2.0 (Roche) with LLQ 25IU/mL. Results: 40 Centres enrolled 737 patients: male 64%; median age 58 (range 18-78), of whom 20.2% over 65; mean BMI 25.6 (range 16-39); Genotype 1b (78.4%); fibrosis F3/4 (70%). DAAs used: Telaprevir (67%); PEGIFN-2a (71%); patients naïve (28%), relapsers (32%), non-responders (40%). Therapy was stopped in 13.4% cases because of side-effects (anaemia 37%, rash 26%) or for virological failure (16.2%). Since the study is ongoing, we have 563 patients who completed the follow-up. The RVR was achieved in 68% cases, EOT in 64%, while the SVR was achieved in 68% in F0-F1; 57% in F2-F3 and 37% in F4. In cirrhotic aging > 65 the SVR was 34%. There were no fatalities. Conclusions: DAAs, in everyday practice, are safe but with moderate efficacy. These data confirm the limited success of DAAs in certain groups of patients such as those widely represented in our series: advanced fibrosis/cirrhosis, non-responders to PEGIFN/RIBA and the over 65s. As for the SVR, the grade of fibrosis makes the difference. http://dx.doi.org/10.1016/j.dld.2015.01.090 T-48 EFFECTIVENESS OF ADALIBUMAB FOR PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE I. Franceschet, N. Cazzagon, A. Floreani Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy Background: Primary sclerosing cholangitis (PSC) is a chronic biliary disease with a marked comorbidity with extra-hepatic conditions, mainly inflammatory bowel disease (IBD). The medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been able to demonstrate efficacy in IBD. Aim: To analyse: 1) the natural history of patients with PSC ± associated with IBD; 2) the long-term efficacy of biologics in patients with PSC and concomitant IBD. Methods: 92 consecutive PSC patients (seen from 1987 to 2014) were included in the study: 50 (54.3%) were males, and 42 (45.7%) females. The mean age at diagnosis was 32.0 ± 14.3 years, and
Events
PSC + IBD (N.49)
PSC-IBD (N.43)
p
OLTx CCA HCC Gallbladder cancer Colo-rectal cancer Death
7 (14.3%) 0 2 (4.1%) 1 (2.0%) 4 (8.2%) 5 (10.2%)
7 (16.3%) 2 (4.6%) 0 0 0 5 (11.6%)
0.79 0.13 0.18 0.35 0.05 0.83
Three patients with IBD experienced, as second-line treatment, Adalimumab (ADA), an anti-TNFa monoclonal antibody, previous written consensus. Patients were assessed before starting treatment, at month 6 and 12. ADA induction was 160 mg at week 0, and then 80 mg at week 2, while ADA maintenance treatment was 40 mg every 2 weeks. After 6 and 12 months of ADA, a sustained clinical remission of IBD was obtained; a reduction in ALT, GGT, alkaline phosphatase and Mayo PSC score was obtained. Conclusions: This is the first study evaluating the efficacy of biologic agents in PSC. Promising results come from ADA for PSC + IBD during a 12 months follow-up. Furthers studies are warranted to investigate the long-term tolerability and efficacy in such patients. http://dx.doi.org/10.1016/j.dld.2015.01.091 T-49 POSITIVE CORRELATION OF HIF2␣ AND SERPINB3 IN HUMAN HEPATOCELLULAR CARCINOMA: SELECTIVITY AND PROGNOSTIC IMPLICATIONS E. Morello 1 , C. Turato 2 , S. Cannito 1 , M. Ruvoletto 2 , S. Quarta 2 , C. Paternostro 1 , E. Novo 1 , R. Autelli 1 , S. Fasolato 2 , I. Tusa 3 , E. Rovida 3 , S. Colombatto 4 , A. Smedile 5 , A. Vitale 6 , G. Zanus 6 , U. Cillo 6 , M. Parola 1 , P. Pontisso 2 1 Department Clinical and Biological Sciences, Unit of Experimental Medicine, University of Turin, Turin, Italy 2 Department Medicine, University of Padua, Padua, Italy 3 Department Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy 4 Department Oncology and 5 Department Medical Sciences, University of Torino, Italy 6 Department Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
Background SerpinB3, a cysteine-proteases inhibitor upregulated in hepatocellular carcinoma (HCC), proposed as biomarker of liver carcinogenesis and to stimulate epithelial-tomesenchymal transition (EMT) and increased invasiveness in liver cancer cells, has been suggested to be up-regulated by hypoxia through a HIF2␣-dependent mechanism. Aims To investigate the selectivity of HIF2␣-related upregulation of SerpinB3 and the in vivo prognostic relevance of this relationships.