- Email: [email protected]
pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection with and without cirrhosis
POSTER PRESENTATIONS FRI-263 Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection with and without cirrhosis K. Chayama1, F. Suzuki2, K. Sato3, T. Atarashi4, T. Watanabe5, H. Toyoda6, M. Atsukawa7, A. Naganuma8, K. Notsumata9, Y. Osaki10, M. Nakamuta11, K. Takaguchi12, S. Saito13, K. Kato14, D.L. Pugatch14, M. Burroughs14, R. Redman14, K. Alves14, T. Pilot-Matias14, B. Fu14, H. Kumada2. 1Hiroshima University Hospital, Hiroshima; 2Toranomon Hospital, Kawasaki; 3Gunma University Hospital, Maebashi; 4JA Hokkaido P.W.F.A.C Obihiro-Kosei General Hospital, Obihiro; 5 St. Marianna University School, Kawasaki; 6Ogaki Municipal Hospital, Ogaki; 7Nippon Medical School Chiba Hokusoh Hospital, Inzai; 8NHO Takasaki General Medical Center, Fukuoka; 9Fukuiken Saiseikai Hospital, Fukui; 10Osaka Red Cross Hospital, Osaka; 11NHO Kyushu Medical Center, Fukuoka; 12Kagawa Prefectural Central Hospital, Takamatsu; 13 Yokohama City University Hospital, Yokohama, Japan; 14AbbVie, North Chicago, United States E-mail: [email protected] Background and Aims: Approximately 1.5 million people are infected with hepatitis C virus in Japan and 30% with genotype 2 (GT2). Two direct-acting antiviral (DAA) regimens are approved for GT2 in Japan including sofosbuvir (SOF) with ribavirin (RBV) and ombitasvir/parataprevir/ritonavir with RBV. The once-daily, all oral, RBV-free, pangenotypic DAA regimen of co-formulated NS3/4A protease inhibitor glecaprevir (GLE, formerly ABT-493, identified by AbbVie and Enanta) and NS5A inhibitor pibrentasvir (PIB, formerly ABT-530), collectively G/P, demonstrated high rates of sustained virologic response (SVR) in studies outside Japan. Here we report safety and efficacy of G/P in GT2 infected Japanese patients including those with cirrhosis. Methods: CERTAIN-2 is a phase 3, open-label, multicenter active comparator study assessing safety and efficacy of G/P 300/120 mg once daily in Japanese non-cirrhotic patients with GT2 infection. Patients were randomized 2:1 to 8 weeks of G/P (Arm A) or 12 weeks of SOF (400 mg QD) + RBV, (600–1000 mg weight-based, divided BID) (Arm B). The primary efficacy endpoint is to demonstrate noninferiority of SVR12 among patients in the intent-to-treat population in Arm A compared to Arm B. Patients with GT2 infection and compensated cirrhosis were enrolled in CERTAIN-1 and assigned to treatment with G/P 300/120 mg once daily for 12 weeks. Here we report virologic response at end of treatment (EOTR) in non-cirrhotic and SVR4 in cirrhotic patients. Results: In Certain-2, 136 patients with GT2 infection without cirrhosis were randomized and treated in Arms A and B. EOTR was 90/90 (100%) for Arm A and 46/46 (100%) for Arm B. 18 GT2 patients with cirrhosis were enrolled in CERTAIN-1 and all (100%) achieved SVR4. One non-cirrhotic patient in each arm experienced a serious adverse event (SAE) and 1 patient in each arm discontinued (DC) treatment due to an AE. Among cirrhotic patients, no SAEs were reported and 1 patient DC treatment due to an AE. Conclusions: EOTR was achieved by 100% GT2 patients without cirrhosis treated with 8 weeks of G/P and 100% treated with 12 weeks of SOF + RBV. SVR4 was achieved by 100% of patients with compensated cirrhosis treated with G/P for 12 weeks. These preliminary results are suggestive of potentially high efficacy and good tolerability of G/P in GT2-infected Japanese patients. SVR12 data will be presented at the conference. FRI-264 Lower sustained virologic response in patients with hepatocellular carcinoma treated for hepatitis C with direct acting antivirals K.T. Nguyen1, P. Konyn1, G. Choi1, F. Durazo1, S.-H. Han1, S. Ramirez1, S. Saab1, M. El-Kabany1. 1UCLA, Los Angeles, United States E-mail: [email protected]
S528
Background and Aims: Direct acting antivirals (DAAs) have made the management of hepatitis C much easier compared to the era of interferon-based therapies. However, there are certain specific populations that DAAs have not yielded great success in curing hepatitis C. Sustained virologic response (SVR) in patients with hepatocellular carcinoma treated for hepatitis C with DAAs is observed to be lower than other patient populations. Methods: We performed a retrospective study of patients with HCCs, treated for hepatitis C with DAAs at the Pfleger Liver Institute at UCLA from February 2014 to April 2016. Laboratory values including Alanine Transaminase (ALT), Aspartate Transaminase (AST), prothrombin time (PT), International Normalized Ratio (INR), serum creatinine, total bilirubin, HCV genotype, HCV RNA viral loads were collected. Data on cirrhosis status and liver imaging were also collected. Patients with coinfection with HBV or HIV were excluded. Results: Of 38 patients that met inclusion criteria, 37/38 (97.4%) were cirrhotic with mean MELD score of 9.7 ± 2.8, 16/38 (42.1%) were treatment experienced, and 16/38 (42.1%) were both cirrhotic and treatment experienced. The mean age was 62.3 ± 8.5 years with 28/38 (73.7%) being male. All patients were treated with DAAs with or without Ribavirin, including 22/38 (57.9%) that were on sofosbuvir and ledipasvir, 5/38 (13.2%) that were on sofosbuvir, ledipasvir, and ribavirin, and 7/38 (18.4%) that were on sofosbuvir and ribavirin. Genotype 1 accounted for 31/38 (81.6%) patients. SVR at 12 weeks after treatment was obtained in 26/38 (68.4%) patients. There were 13/38 (34.2%) patients that were on proton pump inhibitors at the time of treatment. Conclusions: SVR in patients with HCC treated for hepatitis C with DAAs is significantly lower than non-HCC patients treated for hepatitis C, which is well above 95%. Specific protocol and treatment regimen will need to be developed when considering treatment for this particular population of patients. FRI-265 Benefit of direct-acting antiviral therapy in hepatitis C virus (HCV) monoinfected and HIV-HCV coinfected patients with mixed cryoglobulinemia M. Diakite1, K. Hartig-Lavie1, P. Miailhes2, P. Pradat1, A.-C. Uhrès3, F. Zoulim1, M.-N. Sarda4. 1Hepatology, Croix-Rousse Hospital; 2 Infectious Diseases, Croix-Rousse Hospital; 3Pharmacology, CroixRousse Hospital; 4Immunology, Lyon-Sud Hospital, Hospices civils de Lyon, Lyon, France E-mail: [email protected] Background and Aims: Mixed cryoglobulinemia (MC) is found in 40–60% of patients with chronic HCV infection. Direct-acting antiviral (DAA) regimens improve considerably the viral outcome with SVR rates of 90–100%. The rate of cryoglobulin clearance under DAA exposure has rarely been described so far. The objective of this study was to evaluate the efficacy of DAA therapy on cryoglobulin clearance in patients with HCV-associated MC. Methods: Retrospective study of HCV monoinfected and HIV-HCV coinfected patients with symptomatic or non-symptomatic MC who received DAA treatment, followed up from September 2013 to June 2016 in a French University Hospital. Results: 41 patients, 54% males, median age of 58 years [range 35–83] were analyzed. 31 were HCV mono-infected and 10 were HIV-HCV co-infected. HIV patients were all treated by an active combined antiretroviral therapy with HIV viral load <40 copies/mL and median baseline CD4 cell count of 473/mm3 [133–1119]. MC was symptomatic in 77.4% of HCV mono-infected patients and in 10% of HIV-HCV coinfected patients. Two patients had Waldenström macroglobulinemia (WM) and 2 had rheumatoid arthritis (RA). The most frequent symptoms were arthralgia (27%), asthenia (20%) and polyneuropathy (15%). 56% (n = 23) of patients in our cohort were non-responders to PegIFN-Ribavirin (Peg-RBV), 29% (n = 12) were cirrhotics.
Journal of Hepatology 2017 vol. 66 | S333–S542
S528
Background and Aims: Direct acting antivirals (DAAs) have made the management of hepatitis C much easier compared to the era of interferon-based therapies. However, there are certain specific populations that DAAs have not yielded great success in curing hepatitis C. Sustained virologic response (SVR) in patients with hepatocellular carcinoma treated for hepatitis C with DAAs is observed to be lower than other patient populations. Methods: We performed a retrospective study of patients with HCCs, treated for hepatitis C with DAAs at the Pfleger Liver Institute at UCLA from February 2014 to April 2016. Laboratory values including Alanine Transaminase (ALT), Aspartate Transaminase (AST), prothrombin time (PT), International Normalized Ratio (INR), serum creatinine, total bilirubin, HCV genotype, HCV RNA viral loads were collected. Data on cirrhosis status and liver imaging were also collected. Patients with coinfection with HBV or HIV were excluded. Results: Of 38 patients that met inclusion criteria, 37/38 (97.4%) were cirrhotic with mean MELD score of 9.7 ± 2.8, 16/38 (42.1%) were treatment experienced, and 16/38 (42.1%) were both cirrhotic and treatment experienced. The mean age was 62.3 ± 8.5 years with 28/38 (73.7%) being male. All patients were treated with DAAs with or without Ribavirin, including 22/38 (57.9%) that were on sofosbuvir and ledipasvir, 5/38 (13.2%) that were on sofosbuvir, ledipasvir, and ribavirin, and 7/38 (18.4%) that were on sofosbuvir and ribavirin. Genotype 1 accounted for 31/38 (81.6%) patients. SVR at 12 weeks after treatment was obtained in 26/38 (68.4%) patients. There were 13/38 (34.2%) patients that were on proton pump inhibitors at the time of treatment. Conclusions: SVR in patients with HCC treated for hepatitis C with DAAs is significantly lower than non-HCC patients treated for hepatitis C, which is well above 95%. Specific protocol and treatment regimen will need to be developed when considering treatment for this particular population of patients. FRI-265 Benefit of direct-acting antiviral therapy in hepatitis C virus (HCV) monoinfected and HIV-HCV coinfected patients with mixed cryoglobulinemia M. Diakite1, K. Hartig-Lavie1, P. Miailhes2, P. Pradat1, A.-C. Uhrès3, F. Zoulim1, M.-N. Sarda4. 1Hepatology, Croix-Rousse Hospital; 2 Infectious Diseases, Croix-Rousse Hospital; 3Pharmacology, CroixRousse Hospital; 4Immunology, Lyon-Sud Hospital, Hospices civils de Lyon, Lyon, France E-mail: [email protected] Background and Aims: Mixed cryoglobulinemia (MC) is found in 40–60% of patients with chronic HCV infection. Direct-acting antiviral (DAA) regimens improve considerably the viral outcome with SVR rates of 90–100%. The rate of cryoglobulin clearance under DAA exposure has rarely been described so far. The objective of this study was to evaluate the efficacy of DAA therapy on cryoglobulin clearance in patients with HCV-associated MC. Methods: Retrospective study of HCV monoinfected and HIV-HCV coinfected patients with symptomatic or non-symptomatic MC who received DAA treatment, followed up from September 2013 to June 2016 in a French University Hospital. Results: 41 patients, 54% males, median age of 58 years [range 35–83] were analyzed. 31 were HCV mono-infected and 10 were HIV-HCV co-infected. HIV patients were all treated by an active combined antiretroviral therapy with HIV viral load <40 copies/mL and median baseline CD4 cell count of 473/mm3 [133–1119]. MC was symptomatic in 77.4% of HCV mono-infected patients and in 10% of HIV-HCV coinfected patients. Two patients had Waldenström macroglobulinemia (WM) and 2 had rheumatoid arthritis (RA). The most frequent symptoms were arthralgia (27%), asthenia (20%) and polyneuropathy (15%). 56% (n = 23) of patients in our cohort were non-responders to PegIFN-Ribavirin (Peg-RBV), 29% (n = 12) were cirrhotics.
Journal of Hepatology 2017 vol. 66 | S333–S542