- Email: [email protected]
Cirrhosis: Results from a Real World Cohort
POSTER PRESENTATIONS mutation resistance compounds.
during
treatment
with
different
DAA
variceal hemorrhage during treatment and in 2 patients antiviral treatment was stopped due to tumor progression. Patients with virologic failure had mostly been treated with sofosbuvir/ribavirin or sofosbuvir/simeprevir. Conclusions: Antiviral treatment with DAAs is an active therapeutic option in patients with HCV infection and concomitant early and intermediate stage HCC. DAAs were safe and highly effective in patients with HCC after liver transplantation. In non-OLTX patients, SVR rates were lower than reported from patients with less advanced liver disease. The role of antiviral therapy in a multimodal treatment approach of HCC in distinct stages has to be further evaluated. SAT-231 SOFOSBUVIR/DACLATSAVIR/RIBAVIRIN FOR 12 WEEKS IN PATIENTS WITH GENOTYPE 3 HEPATITIS C AND ADVANCED FIBROSIS/ CIRRHOSIS: RESULTS FROM A REAL WORLD COHORT O.F. Ahmed1, F. Marra2, R. Fox2, M. Priest2, S. Datta2, M. Heydtmann3, S.T. Barclay1. 1Walton Liver Clinic, Glasgow Royal Infirmary; 2 Gastroenterology and Hepatology, Queen Elizabeth University Hospital, Glasgow; 3Gastroenterology and Hepatology, Royal Alexander Hospital, Paisley, United Kingdom E-mail: [email protected]
Results: The model was validated against data on SVR12 of 30 completed CT for genotype 1 treatment naïve patients without cirrhosis. Examples of model validation and predictions of SVR12 for ongoing CT are presented in Table. Conclusions: The model satisfactory reproduces SVR12 of completed CT of different DAA combinations used for treatment of HCV patients with GT1. The predictions of SVR12 for ongoing CT were performed and it allows to test the prediction power of model.
Background and Aims: The combination of Sofosbuvir/Daclatasvir/ Ribavirin (Sof/Dac/Rbv) for 12 weeks has shown good clinical efficacy amongst genotype 3 (GT3) patients with advanced fibrosis in a clinical trial setting, and within expanded access programmes (EAP). Outcomes from the use of this combination in routine clinical care are limited. We sought to examine the sustained viral response rates (SVR) of non EAP patients with GT3 infection and F3/4 disease, treated in Glasgow treatment centres.
SAT-230 EFFICACY OF TREATMENT USING DIRECTACTING ANTIVIRAL DRUGS (DAAS) IN HEPATITIS C VIRUS-INFECTED PATIENTS WITH HEPATOCELLULAR CARCINOMA – REAL LIFE DATA O. Waidmann1, M.-W. Welker1, N. Weiler1, S. Zeuzem1, C. Sarrazin1, J. Vermehren1. 1Universitätsklinikum Frankfurt, Frankfurt, Germany E-mail: [email protected] Background and Aims: Antiviral treatment using direct acting antiviral drugs (DAAs) has become the standard of care for patients with chronic hepatitis C virus (HCV) infection in many Western countries. Hepatocellular carcinoma (HCC) is a severe complication of HCV infection and it is associated with a dismal prognosis. Sustained viral response (SVR) following interferon and ribavirin based treatment is associated with decreased rates of HCC recurrence after resection or ablation. As patients with malignant disease are mostly excluded from clinical trials, there is little data of efficacy of HCV treatment using DAAs in HCC patients. Methods: Patients with HCV infection treated with DAAs at our university hospital were prospectively included in a database and underwent follow-up until 12 weeks after the end of antiviral treatment. Among all patients, individuals suffering from HCC were identified and patient’s characteristics, as well as SVR rates were extracted from the database and were analyzed for efficacy of antiviral treatment. Results: In total, 612 HCV infected patients had been treated with DAAs as of September 15, 2015. 52 of the 612 patients were diagnosed with HCC and 12 of the 52 patients had undergone orthotopic liver transplantation (OLTX) before initiation of DAA treatment. The predominant HCV genotype was 1b affecting 21 patients. The tumor stage was BCLC A in 46 patients and BCLC B in 6 patients, respectively. The baseline model of end stage liver disease (MELD) score was 9, ranging from 6 to 23. Overall, 41 of the 52 patients (78.8%) achieved SVR12 and 11 of 12 patients with former OLTX had an SVR12 (91.7%). Concerning the individuals without SVR, 1 of the 11 patients was lost to follow-up, 7 patients relapsed, 1 patient died from S804
Methods: The Scottish Hepatitis C database was examined to identify GT3 patients with F3 (liver stiffness (LSM) > =9.5 kPa <12.5 kPa) or F4 cirrhosis (LSM >12.5 kPa, liver biopsy or imaging) treated in Glasgow treatment centres with Sof/Dac/Rbv for 12 weeks. Demographics, Child’s score, baseline viral load, week 4 and 12 PCR, SVR 4 and SVR12 were recorded, as were adverse events and premature discontinuations. HCV RNA was performed using Abbott Realtime PCR (lower limit of quantification (LLOQ) 12 IU/mL).
Journal of Hepatology 2016 vol. 64 | S631–S832
POSTER PRESENTATIONS Results: 27 patients met the inclusion criteria, 19 (70%) Male, mean age 49.3 (±7.4), 9 (33.3%) treatment experienced. 26/27 (96.3%) were cirrhotic of whom 15 (55.5%)/7 (25.9%)/4 (14.8%) were Child’s A/B/C respectively. 2 patients had HIV co infection, and one was post liver transplant. Median baseline viral load was 4.92 IU/mL (±1.1). At week 4 18 (69%) patients had RNA < 12 IU/mL (8 undetectable, 10 detectable), and 6 (31%) patients had quantifiable viraemia (median 22 IU/mL, range 14–40 IU/mL). Treatment was well tolerated with no discontinuations due to drug related adverse events. One patient’s treatment was stopped after 3 weeks due to an attempted hanging and subsequent psychiatric admission (excluded from SVR analysis), not judged related to treatment. One patient was admitted with variceal bleeding but maintained on treatment and achieved SVR. All patients achieved an end of treatment response (21 undetectable, 5 detectable
seen. 41/45 (91%) of patients have achieved SVR12 (8/8 (100%) treated for 8 weeks), 33/37 (89.1%) of those treated for 12 weeks). Full SVR12 data analysed according to baseline factors will be presented.
Conclusions: Sofosbuvir/Ledipasvir is well tolerated in a difficult to treat real world cohort, with SVR12 rates comparable to clinical trials. SAT-233 DETERMINATION OF LEDIPASVIR CONCENTRATIONS IN PATIENTS WITH DECOMPENSATED CIRRHOSIS RECEIVING LOW DOSE PROTON PUMP INHIBITORS DURING SOFOSBUVIR-LEDIPASVIR TREATMENT FOR HCV GENOTYPE 1 INFECTION O. El-Sherif1,2, S. Stewart3, C. Bergin1,2, S. McKiernan1,2, O. Crosbie4, S. Khoo5, S. Norris1,2. 1St. James’s Hospital; 2Trinity College; 3Mater Hospital, Dublin; 4Cork University Hospital, Cork, Ireland; 5University of Liverpool, Liverpool, United Kingdom E-mail: [email protected] Background and Aims: The combination of sofosbuvir-ledipasvir is associated with high sustained virologic response (SVR) rates in HCV genotype 1 infection, even in patients with decompensated cirrhosis. However, drug-drug interactions remain an important consideration in patients undergoing therapy. Recent real world data has suggested that pre-treatment proton pump inhibitor (PPI) therapy may be associated with a reduced efficacy of therapy containing ledipasvir. The current recommendation is that PPI dosage should be reduced prior to treatment with sofosbuvirledipasvir. Methods: Plasma trough concentrations were prospectively collected in 32 decompensated cirrhotic patients receiving 12 weeks of sofosbuvir-ledipasvir therapy for HCV genotype 1 infection. GS331007 (major circulating metabolite of sofosbuvir) and ledipasvir plasma trough samples were collected at treatment days 7, 14, 28, and 84 and measured using validated LC-MS/MS. 15 patients were receiving PPI therapy at baseline, and had dosage reduction to the equivalent of 20 mg omeprazole or 15 mg lansoprazole, and were advised not to take their PPI prior to the sofosbuvir-ledipasvir dose. Plasma trough levels of ledipasvir were compared in those on PPI therapy vs no PPI therapy. Results: Mean age was 52.81 ± 10.4 and 62.5% were male. The median MELD score was 10 ± 3.2. All patients achieved an on-treatment virologic response, and the SVR12 rate was 87%. There was no
Journal of Hepatology 2016 vol. 64 | S631–S832
S805
during
treatment
with
different
DAA
variceal hemorrhage during treatment and in 2 patients antiviral treatment was stopped due to tumor progression. Patients with virologic failure had mostly been treated with sofosbuvir/ribavirin or sofosbuvir/simeprevir. Conclusions: Antiviral treatment with DAAs is an active therapeutic option in patients with HCV infection and concomitant early and intermediate stage HCC. DAAs were safe and highly effective in patients with HCC after liver transplantation. In non-OLTX patients, SVR rates were lower than reported from patients with less advanced liver disease. The role of antiviral therapy in a multimodal treatment approach of HCC in distinct stages has to be further evaluated. SAT-231 SOFOSBUVIR/DACLATSAVIR/RIBAVIRIN FOR 12 WEEKS IN PATIENTS WITH GENOTYPE 3 HEPATITIS C AND ADVANCED FIBROSIS/ CIRRHOSIS: RESULTS FROM A REAL WORLD COHORT O.F. Ahmed1, F. Marra2, R. Fox2, M. Priest2, S. Datta2, M. Heydtmann3, S.T. Barclay1. 1Walton Liver Clinic, Glasgow Royal Infirmary; 2 Gastroenterology and Hepatology, Queen Elizabeth University Hospital, Glasgow; 3Gastroenterology and Hepatology, Royal Alexander Hospital, Paisley, United Kingdom E-mail: [email protected]
Results: The model was validated against data on SVR12 of 30 completed CT for genotype 1 treatment naïve patients without cirrhosis. Examples of model validation and predictions of SVR12 for ongoing CT are presented in Table. Conclusions: The model satisfactory reproduces SVR12 of completed CT of different DAA combinations used for treatment of HCV patients with GT1. The predictions of SVR12 for ongoing CT were performed and it allows to test the prediction power of model.
Background and Aims: The combination of Sofosbuvir/Daclatasvir/ Ribavirin (Sof/Dac/Rbv) for 12 weeks has shown good clinical efficacy amongst genotype 3 (GT3) patients with advanced fibrosis in a clinical trial setting, and within expanded access programmes (EAP). Outcomes from the use of this combination in routine clinical care are limited. We sought to examine the sustained viral response rates (SVR) of non EAP patients with GT3 infection and F3/4 disease, treated in Glasgow treatment centres.
SAT-230 EFFICACY OF TREATMENT USING DIRECTACTING ANTIVIRAL DRUGS (DAAS) IN HEPATITIS C VIRUS-INFECTED PATIENTS WITH HEPATOCELLULAR CARCINOMA – REAL LIFE DATA O. Waidmann1, M.-W. Welker1, N. Weiler1, S. Zeuzem1, C. Sarrazin1, J. Vermehren1. 1Universitätsklinikum Frankfurt, Frankfurt, Germany E-mail: [email protected] Background and Aims: Antiviral treatment using direct acting antiviral drugs (DAAs) has become the standard of care for patients with chronic hepatitis C virus (HCV) infection in many Western countries. Hepatocellular carcinoma (HCC) is a severe complication of HCV infection and it is associated with a dismal prognosis. Sustained viral response (SVR) following interferon and ribavirin based treatment is associated with decreased rates of HCC recurrence after resection or ablation. As patients with malignant disease are mostly excluded from clinical trials, there is little data of efficacy of HCV treatment using DAAs in HCC patients. Methods: Patients with HCV infection treated with DAAs at our university hospital were prospectively included in a database and underwent follow-up until 12 weeks after the end of antiviral treatment. Among all patients, individuals suffering from HCC were identified and patient’s characteristics, as well as SVR rates were extracted from the database and were analyzed for efficacy of antiviral treatment. Results: In total, 612 HCV infected patients had been treated with DAAs as of September 15, 2015. 52 of the 612 patients were diagnosed with HCC and 12 of the 52 patients had undergone orthotopic liver transplantation (OLTX) before initiation of DAA treatment. The predominant HCV genotype was 1b affecting 21 patients. The tumor stage was BCLC A in 46 patients and BCLC B in 6 patients, respectively. The baseline model of end stage liver disease (MELD) score was 9, ranging from 6 to 23. Overall, 41 of the 52 patients (78.8%) achieved SVR12 and 11 of 12 patients with former OLTX had an SVR12 (91.7%). Concerning the individuals without SVR, 1 of the 11 patients was lost to follow-up, 7 patients relapsed, 1 patient died from S804
Methods: The Scottish Hepatitis C database was examined to identify GT3 patients with F3 (liver stiffness (LSM) > =9.5 kPa <12.5 kPa) or F4 cirrhosis (LSM >12.5 kPa, liver biopsy or imaging) treated in Glasgow treatment centres with Sof/Dac/Rbv for 12 weeks. Demographics, Child’s score, baseline viral load, week 4 and 12 PCR, SVR 4 and SVR12 were recorded, as were adverse events and premature discontinuations. HCV RNA was performed using Abbott Realtime PCR (lower limit of quantification (LLOQ) 12 IU/mL).
Journal of Hepatology 2016 vol. 64 | S631–S832
POSTER PRESENTATIONS Results: 27 patients met the inclusion criteria, 19 (70%) Male, mean age 49.3 (±7.4), 9 (33.3%) treatment experienced. 26/27 (96.3%) were cirrhotic of whom 15 (55.5%)/7 (25.9%)/4 (14.8%) were Child’s A/B/C respectively. 2 patients had HIV co infection, and one was post liver transplant. Median baseline viral load was 4.92 IU/mL (±1.1). At week 4 18 (69%) patients had RNA < 12 IU/mL (8 undetectable, 10 detectable), and 6 (31%) patients had quantifiable viraemia (median 22 IU/mL, range 14–40 IU/mL). Treatment was well tolerated with no discontinuations due to drug related adverse events. One patient’s treatment was stopped after 3 weeks due to an attempted hanging and subsequent psychiatric admission (excluded from SVR analysis), not judged related to treatment. One patient was admitted with variceal bleeding but maintained on treatment and achieved SVR. All patients achieved an end of treatment response (21 undetectable, 5 detectable
seen. 41/45 (91%) of patients have achieved SVR12 (8/8 (100%) treated for 8 weeks), 33/37 (89.1%) of those treated for 12 weeks). Full SVR12 data analysed according to baseline factors will be presented.
Conclusions: Sofosbuvir/Ledipasvir is well tolerated in a difficult to treat real world cohort, with SVR12 rates comparable to clinical trials. SAT-233 DETERMINATION OF LEDIPASVIR CONCENTRATIONS IN PATIENTS WITH DECOMPENSATED CIRRHOSIS RECEIVING LOW DOSE PROTON PUMP INHIBITORS DURING SOFOSBUVIR-LEDIPASVIR TREATMENT FOR HCV GENOTYPE 1 INFECTION O. El-Sherif1,2, S. Stewart3, C. Bergin1,2, S. McKiernan1,2, O. Crosbie4, S. Khoo5, S. Norris1,2. 1St. James’s Hospital; 2Trinity College; 3Mater Hospital, Dublin; 4Cork University Hospital, Cork, Ireland; 5University of Liverpool, Liverpool, United Kingdom E-mail: [email protected] Background and Aims: The combination of sofosbuvir-ledipasvir is associated with high sustained virologic response (SVR) rates in HCV genotype 1 infection, even in patients with decompensated cirrhosis. However, drug-drug interactions remain an important consideration in patients undergoing therapy. Recent real world data has suggested that pre-treatment proton pump inhibitor (PPI) therapy may be associated with a reduced efficacy of therapy containing ledipasvir. The current recommendation is that PPI dosage should be reduced prior to treatment with sofosbuvirledipasvir. Methods: Plasma trough concentrations were prospectively collected in 32 decompensated cirrhotic patients receiving 12 weeks of sofosbuvir-ledipasvir therapy for HCV genotype 1 infection. GS331007 (major circulating metabolite of sofosbuvir) and ledipasvir plasma trough samples were collected at treatment days 7, 14, 28, and 84 and measured using validated LC-MS/MS. 15 patients were receiving PPI therapy at baseline, and had dosage reduction to the equivalent of 20 mg omeprazole or 15 mg lansoprazole, and were advised not to take their PPI prior to the sofosbuvir-ledipasvir dose. Plasma trough levels of ledipasvir were compared in those on PPI therapy vs no PPI therapy. Results: Mean age was 52.81 ± 10.4 and 62.5% were male. The median MELD score was 10 ± 3.2. All patients achieved an on-treatment virologic response, and the SVR12 rate was 87%. There was no
Journal of Hepatology 2016 vol. 64 | S631–S832
S805