- Email: [email protected]
Cirrhosis regression does not prevent hepatocellular carcinoma in patients with a sustained virological response to IFN
Abstracts / Digestive and Liver Disease 49S (2017) e19–e42
Fig. 1.
CI: 1.73–3.24), platelets count (abnormal vs normal; HR = 2.45, CI: 1.72–3.5), ‘delta ALP’ after twelve months of treatment with UDCA and bilirubin (log-scale). Only for ‘delta ALP’ and bilirubin a time dependent effect was detected and estimated together with a confidence band (Fig. 1). Conclusions: We identified the time-dependent effect of previously known predictive variables. Elevated bilirubin strongly predicts adverse outcome but the risk conferred declines with time. The risk of ‘delta ALP’ after treatment with UDCA has a slight increase over the time. Accounting for time-dependency we can improve the accuracy of existing prognostic models. Dynamic prediction modelling represents a high-performance statistical tool to support decision-making in patients with PBC in need of intensive monitoring and care. http://dx.doi.org/10.1016/j.dld.2017.01.069 T-32 Established cirrhosis at the time of diagnosis predicts adverse outcome in autoimmune hepatitis: A retrospective cohort study A. Gerussi 1,2 , N. Halliday 3 , D. Roccarina 1 , F. Saffioti 1,4 , P. Polly 1 , M. Pinzani 1 , A. Marshall 1 , D. Thorburn 1 1
UCL Institute for Liver and Digestive Health, The Royal Free Sheila Sherlock Centre, Royal Free Hospital, London, United Kingdom 2 Department of Experimental and Clinical Medical Sciences, Liver Unit, Clinica Medica, Udine, Italy 3 Institute of Immunity and Transplantation, UCL, London, United Kingdom 4 Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy Introduction: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death.
e33
Aim: To identify those clinical parameters which, when present at diagnosis, predict liver transplant (LT) or death in AIH patients. Materials and methods: Data from a retrospective database of all patients with AIH, attending a tertiary liver unit since 1980, were used. Patients who did not meet IAIHG diagnostic criteria or had other concomitant liver diseases, acute liver failure at onset, incomplete data or less than 1 month follow up were excluded. Cases were censored at the endpoint of death or LT. Results: 137 patients were included, of which 39 had histologically-proven cirrhosis, 16 reached the endpoint of death or LT. Only 3 non cirrhotic patients reached the endpoint. Median follow up since diagnosis was 62 months (IQR 121). Univariate Cox regression analysis identified that histologically-proven cirrhosis (HR 12.2, p < 0.0001) correlated with adverse outcome, while higher ALT (HR 0.012, p < 0.027) was associated with reduced risk of adverse outcomes. Histological cirrhosis significantly increased the risk of death or LT on multivariate Cox regression analysis (HR 14.6, p < 0.001) and was associated with reduced LT-free survival (159 months vs 354 months respectively, p < 0.0001, log rank). On univariate analysis, lower ALT, albumin and INR at diagnosis were significantly associated with histological cirrhosis. Lower serum albumin (OR 0.905, p < 0.013) and ALT (OR 0.998, p < 0.001) showed a significant independent association with cirrhosis on binary logistic regression. Conclusions: Histological cirrhosis at diagnosis was a significant independent predictor of all-cause death or LT. Patients with cirrhosis at presentation had lower ALT levels and lower albumin than those without cirrhosis. The degree of elevation of transaminases and hepatic synthetic dysfunction was not associated with adverse outcomes, suggesting that presence of cirrhosis is the predominant factor in determining patient outcomes. http://dx.doi.org/10.1016/j.dld.2017.01.070 T-33 Cirrhosis regression does not prevent hepatocellular carcinoma in patients with a sustained virological response to IFN R. D’Ambrosio 1 , A. Aghemo 1 , E. Degasperi 1 , A. Sangiovanni 1 , M.G. Rumi 2 , M. Fraquelli 3 , R. Perbellini 1 , P. Bedossa 4 , M. Colombo 5 , P. Lampertico 1 1
A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy 2 Department of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy 3 Department of Gastroenterology and Endoscopy, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy 4 Department of Pathology and INSERM U773, Beaujon Hopital, Universitée Paris-Diderot, Clichy, France 5 Center for Translational Hepatology Research, IRCCS Humanitas Hospital and University, Rozzano, Italy Introduction: Sustained virological response (SVR) to antiHCV treatments is associated with fibrosis re-absorption, cirrhosis regression (CR) and reduced risk of cirrhosis-related complications. Whether the histological changes associated with SVR have any impact on the incidence of cirrhosis complications is still unknown.
e34
Abstracts / Digestive and Liver Disease 49S (2017) e19–e42
Aim: To prospectively assess the incidence of liver-related events in a cohort of HCV cirrhotic SVR patients with an SVR and post-SVR histological assessment. Methods: We followed-up with 6-month HCC surveillance and clinical evaluation a previously published cohort of 38 cirrhotics with paired pre- and post-SVR liver biopsies (D’Ambrosio R, Hepatology 2012). At post-SVR liver biopsy (LB), 15 (39%) achieved CR (METAVIR). Results: After 69 (7–88) months of follow-up after LB, no episodes of clinical decompensation or GI-bleeding were recorded in our cohort, whilst 5 (13%) patients developed hepatocellular carcinoma (HCC). The rates of HCC were similar in patients with and without CR (3/21 vs. 2/15: 14% vs. 13%, p = 1.0). Histological findings didn’t differ between patients who developed or didn’t develop HCC. In fact, among them rates of residual cirrhosis (40% vs. 40%, p = 1.0), collagen content [2.4 (1.7–5.9) % vs. 2.3 (0.6–15.1%), p = 0.48] METAVIR activity (p = 0.34), residual portal inflammation (p = 0.06) and steatosis (40% vs. 12%, p = 0.17) were similar. Similarly, we observed no difference in immunochemistry (CK7, GS, ASMA, CD34, CYP2E1). Clinical features and biochemical parameters were similar in patients with and without HCC; only gGT remained higher in the former group [median 46 (21–57) U/l vs. 23 (14–142) U/l, p = 0.05]. The 5-year survival rates were the same, independently on CR (96% vs. 100%, p = 1.0) or HCC development (100% vs. 97%, p = 1.0). One CR patient died of non-liver related complications, whilst no cases of cirrhosis-related deaths were recorded. Conclusions: Post-SVR histological assessment in HCV compensated cirrhotics does not predict HCC risk within 5 years. http://dx.doi.org/10.1016/j.dld.2017.01.071 T-34 Impact of von Willebrand factor and ADAMTS-13 on the pro-coagulant imbalance of patients with cirrhosis V. La Mura 1,2 , A. Tripodi 3 , N. Bitto 1 , G. Tosetti 2 , V. Chantarangkul 3 , L. Baronciani 3 , C. Valsecchi 3 , F. Peyvandi 3 , F. Salerno 1 , P. Lampertico 2 , M. Colombo 2 , M. Primignani 2 1
Internal Medicine-IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy 2 Division of Gastroenterology and Hepatology-IRCCS Ca’ Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy 3 Angelo Bianchi Bonomi Hemophilia and Thrombosis Center-IRCCS Ca’ Granda Maggiore Hospital Foundation, Department of Clinical, Sciences and Community Health, University of Milan, Milan, Italy Introduction: Von Willebrand factor (VWF) is an independent predictor of clinical outcome in cirrhosis confirming the potential pathogenic role of hemostasis on liver damage. Aim: The study explored: 1 – the association between VWF and thrombomodulin-resistance (TM-R), 2 – the impact of ADAMTS-13 on VWF along with the severity of the liver disease. Material and methods Results: Prospective collection of clinical and laboratory data of 79 patients (n◦ Child A/B/C = 29/35/15) consecutively admitted for endoscopic band ligation of esophageal varices/paracentesis. All patients were in stable hemodynamic conditions and without clinical evidence of bacterial infection. Examinations included VWF (antigen, VWF:Ag, and activity, VWF:RCo) (VWF:RCo/VWF:Ag was an estimate of highly active
VWF), ADAMTS-13 activity, the main pro-(FVIII, FII) and anticoagulants (antithrombin, protein C). ETP-ratio (Endogenous thrombin Potential) with/without thrombomodulin defined the degree of TM-R and was used to explore the influence of VWF on pro-coagulant imbalance. Liver dysfunction correlated with high VWF:Ag, VWF:RCO and low ADAMTS-13 (p < 0.05). FVIII was the factor with the highest degree of association with VWF:Ag and VWF:RCO independently from MELD or Child-Pugh (multiple linear regression; p < 0.001) in accordance with the biological role of VWF protecting FVIII from degradation. ADAMTS-13 negatively correlated with VWF:RCO/VWF:Ag ratio, an indirect estimation of VWF multimers. The thrombin generation curve of patients with high VWF:Ag disclosed the lowest lag-time and time-to-peak suggesting high reactivity for thrombin generation. VWF positively correlated with the degree of TM-R independently from the severity of liver disease. Furthermore, it identified the highest proportion of patients with TM-R over 0.78 units, the threshold of risk for thrombosis and severe clinical outcome recently described in a retrospective study of patients with cirrhosis. By contrary ADAMTS-13 was not associated with TM-R. Conclusions: VWF/ADAMTS-13 axis is impaired along with the severity of liver dysfunction. VWF significantly influences the procoagulant imbalance detected in cirrhosis through high levels of FVIII. http://dx.doi.org/10.1016/j.dld.2017.01.072 T-35 DAA-based regimens in HBsAg/anti-HCV positive patients: The need to control HBV replication to avoid HBV reactivation M. Macera 1 , M. Stanzione 1 , V. Messina 2 , G. D’Adamo 3 , V. Sangiovanni 4 , L. Fontanella 5 , S. De Pascalis 1 , G. Stornaiuolo 1 , G. Piai 6 , G.B. Gaeta 1 , I. Gentile 7 , N. Coppola 1 1 Public Medicine, Second University of Naples, Naples, Italy 2 AO Caserta, Caserta, Italy 3 AO Nocera, Nocera, Italy 4 AO Cotugno, Naples, Italy 5 AO Fatebenefratelli, Naples, Italy 6 Gastroenterology, AO Caserta, Italy 7 Infectious diseases, Federico II University, Naples, Italy
Background: The aim of the present study was to evaluate the efficacy of Direct Antiviral Agents (DAA)-based regimen in HBsAg/anti-HCV/HCV-RNA-positive patients (pts) with chronic liver disease in terms of sustained virolgical response for HCV and of reactivation of HBV infection. Methods: We enrolled 16 HBsAg-positive pts with antiHCV/HCV-RNA positive-related chronic liver diseases, treated with DAA [median age 61 years (IQR 44–65), 11 males, 10 with cirrhosis (Child A in 9), only 1 post-liver transplant]. Regarding the HBV infection, only one patient was HBeAg-positive, all anti-HDVnegative. At the time when DAA was started, 11 pts were treated with Entecavir from 1-36 months (all HBV-DNA negative; NUC-tx group) and 5 pts not [NUC-sparing group: HBV-DNA was negative in 4 and positive in 1 (577 IU/ml)]. All patients were monitored for HCV-RNA and HBV-DNA every month during the treatment and for 6 months after the stop. Result: Of the 16 patients enrolled, 14 (87.5%) showed a HCVSVR and 2 a relapse. In NUC-tx group, all pts remained HBV-DA negative. Of the 5 pts in NUC-sparing group, 2 pts remained HBV-
Fig. 1.
CI: 1.73–3.24), platelets count (abnormal vs normal; HR = 2.45, CI: 1.72–3.5), ‘delta ALP’ after twelve months of treatment with UDCA and bilirubin (log-scale). Only for ‘delta ALP’ and bilirubin a time dependent effect was detected and estimated together with a confidence band (Fig. 1). Conclusions: We identified the time-dependent effect of previously known predictive variables. Elevated bilirubin strongly predicts adverse outcome but the risk conferred declines with time. The risk of ‘delta ALP’ after treatment with UDCA has a slight increase over the time. Accounting for time-dependency we can improve the accuracy of existing prognostic models. Dynamic prediction modelling represents a high-performance statistical tool to support decision-making in patients with PBC in need of intensive monitoring and care. http://dx.doi.org/10.1016/j.dld.2017.01.069 T-32 Established cirrhosis at the time of diagnosis predicts adverse outcome in autoimmune hepatitis: A retrospective cohort study A. Gerussi 1,2 , N. Halliday 3 , D. Roccarina 1 , F. Saffioti 1,4 , P. Polly 1 , M. Pinzani 1 , A. Marshall 1 , D. Thorburn 1 1
UCL Institute for Liver and Digestive Health, The Royal Free Sheila Sherlock Centre, Royal Free Hospital, London, United Kingdom 2 Department of Experimental and Clinical Medical Sciences, Liver Unit, Clinica Medica, Udine, Italy 3 Institute of Immunity and Transplantation, UCL, London, United Kingdom 4 Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy Introduction: Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure and death.
e33
Aim: To identify those clinical parameters which, when present at diagnosis, predict liver transplant (LT) or death in AIH patients. Materials and methods: Data from a retrospective database of all patients with AIH, attending a tertiary liver unit since 1980, were used. Patients who did not meet IAIHG diagnostic criteria or had other concomitant liver diseases, acute liver failure at onset, incomplete data or less than 1 month follow up were excluded. Cases were censored at the endpoint of death or LT. Results: 137 patients were included, of which 39 had histologically-proven cirrhosis, 16 reached the endpoint of death or LT. Only 3 non cirrhotic patients reached the endpoint. Median follow up since diagnosis was 62 months (IQR 121). Univariate Cox regression analysis identified that histologically-proven cirrhosis (HR 12.2, p < 0.0001) correlated with adverse outcome, while higher ALT (HR 0.012, p < 0.027) was associated with reduced risk of adverse outcomes. Histological cirrhosis significantly increased the risk of death or LT on multivariate Cox regression analysis (HR 14.6, p < 0.001) and was associated with reduced LT-free survival (159 months vs 354 months respectively, p < 0.0001, log rank). On univariate analysis, lower ALT, albumin and INR at diagnosis were significantly associated with histological cirrhosis. Lower serum albumin (OR 0.905, p < 0.013) and ALT (OR 0.998, p < 0.001) showed a significant independent association with cirrhosis on binary logistic regression. Conclusions: Histological cirrhosis at diagnosis was a significant independent predictor of all-cause death or LT. Patients with cirrhosis at presentation had lower ALT levels and lower albumin than those without cirrhosis. The degree of elevation of transaminases and hepatic synthetic dysfunction was not associated with adverse outcomes, suggesting that presence of cirrhosis is the predominant factor in determining patient outcomes. http://dx.doi.org/10.1016/j.dld.2017.01.070 T-33 Cirrhosis regression does not prevent hepatocellular carcinoma in patients with a sustained virological response to IFN R. D’Ambrosio 1 , A. Aghemo 1 , E. Degasperi 1 , A. Sangiovanni 1 , M.G. Rumi 2 , M. Fraquelli 3 , R. Perbellini 1 , P. Bedossa 4 , M. Colombo 5 , P. Lampertico 1 1
A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy 2 Department of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy 3 Department of Gastroenterology and Endoscopy, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy 4 Department of Pathology and INSERM U773, Beaujon Hopital, Universitée Paris-Diderot, Clichy, France 5 Center for Translational Hepatology Research, IRCCS Humanitas Hospital and University, Rozzano, Italy Introduction: Sustained virological response (SVR) to antiHCV treatments is associated with fibrosis re-absorption, cirrhosis regression (CR) and reduced risk of cirrhosis-related complications. Whether the histological changes associated with SVR have any impact on the incidence of cirrhosis complications is still unknown.
e34
Abstracts / Digestive and Liver Disease 49S (2017) e19–e42
Aim: To prospectively assess the incidence of liver-related events in a cohort of HCV cirrhotic SVR patients with an SVR and post-SVR histological assessment. Methods: We followed-up with 6-month HCC surveillance and clinical evaluation a previously published cohort of 38 cirrhotics with paired pre- and post-SVR liver biopsies (D’Ambrosio R, Hepatology 2012). At post-SVR liver biopsy (LB), 15 (39%) achieved CR (METAVIR). Results: After 69 (7–88) months of follow-up after LB, no episodes of clinical decompensation or GI-bleeding were recorded in our cohort, whilst 5 (13%) patients developed hepatocellular carcinoma (HCC). The rates of HCC were similar in patients with and without CR (3/21 vs. 2/15: 14% vs. 13%, p = 1.0). Histological findings didn’t differ between patients who developed or didn’t develop HCC. In fact, among them rates of residual cirrhosis (40% vs. 40%, p = 1.0), collagen content [2.4 (1.7–5.9) % vs. 2.3 (0.6–15.1%), p = 0.48] METAVIR activity (p = 0.34), residual portal inflammation (p = 0.06) and steatosis (40% vs. 12%, p = 0.17) were similar. Similarly, we observed no difference in immunochemistry (CK7, GS, ASMA, CD34, CYP2E1). Clinical features and biochemical parameters were similar in patients with and without HCC; only gGT remained higher in the former group [median 46 (21–57) U/l vs. 23 (14–142) U/l, p = 0.05]. The 5-year survival rates were the same, independently on CR (96% vs. 100%, p = 1.0) or HCC development (100% vs. 97%, p = 1.0). One CR patient died of non-liver related complications, whilst no cases of cirrhosis-related deaths were recorded. Conclusions: Post-SVR histological assessment in HCV compensated cirrhotics does not predict HCC risk within 5 years. http://dx.doi.org/10.1016/j.dld.2017.01.071 T-34 Impact of von Willebrand factor and ADAMTS-13 on the pro-coagulant imbalance of patients with cirrhosis V. La Mura 1,2 , A. Tripodi 3 , N. Bitto 1 , G. Tosetti 2 , V. Chantarangkul 3 , L. Baronciani 3 , C. Valsecchi 3 , F. Peyvandi 3 , F. Salerno 1 , P. Lampertico 2 , M. Colombo 2 , M. Primignani 2 1
Internal Medicine-IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy 2 Division of Gastroenterology and Hepatology-IRCCS Ca’ Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy 3 Angelo Bianchi Bonomi Hemophilia and Thrombosis Center-IRCCS Ca’ Granda Maggiore Hospital Foundation, Department of Clinical, Sciences and Community Health, University of Milan, Milan, Italy Introduction: Von Willebrand factor (VWF) is an independent predictor of clinical outcome in cirrhosis confirming the potential pathogenic role of hemostasis on liver damage. Aim: The study explored: 1 – the association between VWF and thrombomodulin-resistance (TM-R), 2 – the impact of ADAMTS-13 on VWF along with the severity of the liver disease. Material and methods Results: Prospective collection of clinical and laboratory data of 79 patients (n◦ Child A/B/C = 29/35/15) consecutively admitted for endoscopic band ligation of esophageal varices/paracentesis. All patients were in stable hemodynamic conditions and without clinical evidence of bacterial infection. Examinations included VWF (antigen, VWF:Ag, and activity, VWF:RCo) (VWF:RCo/VWF:Ag was an estimate of highly active
VWF), ADAMTS-13 activity, the main pro-(FVIII, FII) and anticoagulants (antithrombin, protein C). ETP-ratio (Endogenous thrombin Potential) with/without thrombomodulin defined the degree of TM-R and was used to explore the influence of VWF on pro-coagulant imbalance. Liver dysfunction correlated with high VWF:Ag, VWF:RCO and low ADAMTS-13 (p < 0.05). FVIII was the factor with the highest degree of association with VWF:Ag and VWF:RCO independently from MELD or Child-Pugh (multiple linear regression; p < 0.001) in accordance with the biological role of VWF protecting FVIII from degradation. ADAMTS-13 negatively correlated with VWF:RCO/VWF:Ag ratio, an indirect estimation of VWF multimers. The thrombin generation curve of patients with high VWF:Ag disclosed the lowest lag-time and time-to-peak suggesting high reactivity for thrombin generation. VWF positively correlated with the degree of TM-R independently from the severity of liver disease. Furthermore, it identified the highest proportion of patients with TM-R over 0.78 units, the threshold of risk for thrombosis and severe clinical outcome recently described in a retrospective study of patients with cirrhosis. By contrary ADAMTS-13 was not associated with TM-R. Conclusions: VWF/ADAMTS-13 axis is impaired along with the severity of liver dysfunction. VWF significantly influences the procoagulant imbalance detected in cirrhosis through high levels of FVIII. http://dx.doi.org/10.1016/j.dld.2017.01.072 T-35 DAA-based regimens in HBsAg/anti-HCV positive patients: The need to control HBV replication to avoid HBV reactivation M. Macera 1 , M. Stanzione 1 , V. Messina 2 , G. D’Adamo 3 , V. Sangiovanni 4 , L. Fontanella 5 , S. De Pascalis 1 , G. Stornaiuolo 1 , G. Piai 6 , G.B. Gaeta 1 , I. Gentile 7 , N. Coppola 1 1 Public Medicine, Second University of Naples, Naples, Italy 2 AO Caserta, Caserta, Italy 3 AO Nocera, Nocera, Italy 4 AO Cotugno, Naples, Italy 5 AO Fatebenefratelli, Naples, Italy 6 Gastroenterology, AO Caserta, Italy 7 Infectious diseases, Federico II University, Naples, Italy
Background: The aim of the present study was to evaluate the efficacy of Direct Antiviral Agents (DAA)-based regimen in HBsAg/anti-HCV/HCV-RNA-positive patients (pts) with chronic liver disease in terms of sustained virolgical response for HCV and of reactivation of HBV infection. Methods: We enrolled 16 HBsAg-positive pts with antiHCV/HCV-RNA positive-related chronic liver diseases, treated with DAA [median age 61 years (IQR 44–65), 11 males, 10 with cirrhosis (Child A in 9), only 1 post-liver transplant]. Regarding the HBV infection, only one patient was HBeAg-positive, all anti-HDVnegative. At the time when DAA was started, 11 pts were treated with Entecavir from 1-36 months (all HBV-DNA negative; NUC-tx group) and 5 pts not [NUC-sparing group: HBV-DNA was negative in 4 and positive in 1 (577 IU/ml)]. All patients were monitored for HCV-RNA and HBV-DNA every month during the treatment and for 6 months after the stop. Result: Of the 16 patients enrolled, 14 (87.5%) showed a HCVSVR and 2 a relapse. In NUC-tx group, all pts remained HBV-DA negative. Of the 5 pts in NUC-sparing group, 2 pts remained HBV-