- Email: [email protected]
Survival and recurrences after curative treatments of HCV-related early hepatocellular carcinoma. A meta-analysis of single arm studies
Abstracts / Digestive and Liver Disease 49S (2017) e43–e70
F-34 Survival and recurrences after curative treatments of HCV-related early hepatocellular carcinoma. A meta-analysis of single arm studies G. Cabibbo 1 , S. Petta 1 , M. Barbàra 1 , G. Missale 2 , R. Virdone 3 , E. Caturelli 4 , F. Piscaglia 5 , F. Morisco 6 , A. Colecchia 7 , F. Farinati 8 , E. Giannini 9 , F. Trevisani 10 , A. Craxì 1 , M. Colombo 11 , C. Cammà 1 , on behalf of the ITA.LI.CA study group 1 Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Italy 2 Unit of Infectious Diseases and Hepatology, Teaching Hospital-University of Parma, Italy 3 Division of Internal Medicine 2, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy 4 Division of Gastroenterology, Belcolle Hospital, Viterbo, Italy 5 Division of Internal Medicine, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy 6 Division of Gastroenterology, Department of Medicine and Surgery, University of Naples Federico II, Italy 7 Department of Medical and Surgical Sciences, University of Bologna, Italy 8 Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy 9 Gastroenterology Unit, Department of Internal Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino IST, University of Genoa, Italy 10 Division of Semeiotics, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy 11 A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Maggiore Hospital, University of Milan, Italy
Background and aims: Knowing risk for recurrence and survival after curative resection or ablation in patients with HCVrelated hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct acting antivirals (DAA). The aims of this meta-analysis were to estimate recurrence and survival probability of HCV-related early HCC who achieved complete response after curative treatments and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after curative treatment of HCV-related early HCC were identified on MEDLINE through May 2016. Data on the patient populations and outcomes were extracted from each study by three independent observers and combined by a distributionfree summary survival curve. Primary outcomes were actuarial probability of recurrence and survival. Results: Eleven studies met the inclusion criteria. The pooled estimates of actuarial recurrence rates were 7.4% at 6 months and 47.0% at 2 years. The pooled estimates of actuarial survival rates were 79.8% at 3 years and 58.6% at 5 years. Heterogeneity among studies was highly significant for all outcomes. By univariate metaregression analyses, lower serum albumin, study design and followup were independently associated with higher risk of recurrence, while tumor size and alpha-fetoprotein with higher mortality.
e61
Conclusions: This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefit of DAA and for a correct design of RCT in the adjuvant setting. http://dx.doi.org/10.1016/j.dld.2017.01.122 F-35 Are detectable sofosbuvir trough concentrations predictive of virological failure during anti-HCV treatment? Preliminary evidences from the KINETI-C study A. De Nicolò, L. Boglione, C. Carcieri, J. Cusato, S. Mornese Pinna, F. Favata, A. Ariaudo, G. Di Perri, A. D’Avolio Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: In the current standard of care for HCV infection, sofosbuvir (SOF) represents the backbone of several therapeutic regimens. Up to now, pharmacokinetic/pharmacodynamic properties of SOF, as well as other DAAs, have been poorly studied in “real-life” settings. SOF is a prodrug, which is firstly converted in its active metabolite and is then measurable in plasma as its main metabolite GS-331007. In fact, the fast conversion of SOF makes GS-331007 the best marker of SOF exposure. Aim: The aim of this study was to investigate pharmacokinetic data in a real-life clinical context to identify possible predictors of virological failure. Materials and methods: HCV infected patients in treatment with SOF-based regimens were enrolled in “Kineti-C” clinical study. SOF, GS-331007 and concomitant drug concentrations were measured at 1, 3, 7, 30 and 60 days of treatment, through validated methods in UHPLC–MS/MS. Statistical analysis was performed through SPSS 22.0 statistical software. P values lower than 0.05 were considered as statistically significant. Results: 95 patients who received SOF in their anti-HCV therapy were enrolled: 37.9% (36) with SOF/DCV; 27.4% (26) with SOF/SMV; 23.2% (22) with SOF/LPV; 9.5% (9) with SOF/RBV; 2.1% (2) with SOF/RBV/PEG-IFN.SOF Ctrough was detectable at least at one timing for 6 patients. Detectable SOF concentrations resulted significantly associated to the onset of breakthrough (2 cases out of 3; P-value = 0.000013). GS-331007 and other drugs concentrations resulted not significantly correlated with treatment response. Conclusions: A residual Ctrough of SOF might underlie an incomplete conversion of SOF to its active metabolites: this could lead to a lower activity than expected. Further studies are needed to clarify the reasons behind the SOF detectable determinations and consequent clinical implications. Anyway, this tool could be useful to the clinicians for the early identification of the residual rare cases of virological failure. http://dx.doi.org/10.1016/j.dld.2017.01.123
F-34 Survival and recurrences after curative treatments of HCV-related early hepatocellular carcinoma. A meta-analysis of single arm studies G. Cabibbo 1 , S. Petta 1 , M. Barbàra 1 , G. Missale 2 , R. Virdone 3 , E. Caturelli 4 , F. Piscaglia 5 , F. Morisco 6 , A. Colecchia 7 , F. Farinati 8 , E. Giannini 9 , F. Trevisani 10 , A. Craxì 1 , M. Colombo 11 , C. Cammà 1 , on behalf of the ITA.LI.CA study group 1 Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Italy 2 Unit of Infectious Diseases and Hepatology, Teaching Hospital-University of Parma, Italy 3 Division of Internal Medicine 2, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy 4 Division of Gastroenterology, Belcolle Hospital, Viterbo, Italy 5 Division of Internal Medicine, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy 6 Division of Gastroenterology, Department of Medicine and Surgery, University of Naples Federico II, Italy 7 Department of Medical and Surgical Sciences, University of Bologna, Italy 8 Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy 9 Gastroenterology Unit, Department of Internal Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino IST, University of Genoa, Italy 10 Division of Semeiotics, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy 11 A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Maggiore Hospital, University of Milan, Italy
Background and aims: Knowing risk for recurrence and survival after curative resection or ablation in patients with HCVrelated hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct acting antivirals (DAA). The aims of this meta-analysis were to estimate recurrence and survival probability of HCV-related early HCC who achieved complete response after curative treatments and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after curative treatment of HCV-related early HCC were identified on MEDLINE through May 2016. Data on the patient populations and outcomes were extracted from each study by three independent observers and combined by a distributionfree summary survival curve. Primary outcomes were actuarial probability of recurrence and survival. Results: Eleven studies met the inclusion criteria. The pooled estimates of actuarial recurrence rates were 7.4% at 6 months and 47.0% at 2 years. The pooled estimates of actuarial survival rates were 79.8% at 3 years and 58.6% at 5 years. Heterogeneity among studies was highly significant for all outcomes. By univariate metaregression analyses, lower serum albumin, study design and followup were independently associated with higher risk of recurrence, while tumor size and alpha-fetoprotein with higher mortality.
e61
Conclusions: This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefit of DAA and for a correct design of RCT in the adjuvant setting. http://dx.doi.org/10.1016/j.dld.2017.01.122 F-35 Are detectable sofosbuvir trough concentrations predictive of virological failure during anti-HCV treatment? Preliminary evidences from the KINETI-C study A. De Nicolò, L. Boglione, C. Carcieri, J. Cusato, S. Mornese Pinna, F. Favata, A. Ariaudo, G. Di Perri, A. D’Avolio Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: In the current standard of care for HCV infection, sofosbuvir (SOF) represents the backbone of several therapeutic regimens. Up to now, pharmacokinetic/pharmacodynamic properties of SOF, as well as other DAAs, have been poorly studied in “real-life” settings. SOF is a prodrug, which is firstly converted in its active metabolite and is then measurable in plasma as its main metabolite GS-331007. In fact, the fast conversion of SOF makes GS-331007 the best marker of SOF exposure. Aim: The aim of this study was to investigate pharmacokinetic data in a real-life clinical context to identify possible predictors of virological failure. Materials and methods: HCV infected patients in treatment with SOF-based regimens were enrolled in “Kineti-C” clinical study. SOF, GS-331007 and concomitant drug concentrations were measured at 1, 3, 7, 30 and 60 days of treatment, through validated methods in UHPLC–MS/MS. Statistical analysis was performed through SPSS 22.0 statistical software. P values lower than 0.05 were considered as statistically significant. Results: 95 patients who received SOF in their anti-HCV therapy were enrolled: 37.9% (36) with SOF/DCV; 27.4% (26) with SOF/SMV; 23.2% (22) with SOF/LPV; 9.5% (9) with SOF/RBV; 2.1% (2) with SOF/RBV/PEG-IFN.SOF Ctrough was detectable at least at one timing for 6 patients. Detectable SOF concentrations resulted significantly associated to the onset of breakthrough (2 cases out of 3; P-value = 0.000013). GS-331007 and other drugs concentrations resulted not significantly correlated with treatment response. Conclusions: A residual Ctrough of SOF might underlie an incomplete conversion of SOF to its active metabolites: this could lead to a lower activity than expected. Further studies are needed to clarify the reasons behind the SOF detectable determinations and consequent clinical implications. Anyway, this tool could be useful to the clinicians for the early identification of the residual rare cases of virological failure. http://dx.doi.org/10.1016/j.dld.2017.01.123