Sustained Virological Response in HCV Patients Treated with Daclatasvir+Sofosbuvir, with or without Ribavirin: A Multicenter, Field-Practice Experience

in three of the phase 3 trials (ASTRAL 1, 2 & 3), 123 (12%) were ≥ 65 years old, of whom 87 were GT 2-6. SVR12 was achieved by 97.8% (892/912) of subjects aged < 65 years and 100% (123/123) of subjects aged ≥ 65 years. The most common AEs that occurred in ≥ 10% of subjects age ≥65 and <65 were headache (23.6% v 29.3%), fatigue (20.3% v 21.3%), nausea (13.8% v 13.0%), and nasopharyngitis (9.8% v 12.3%), respectively. No subjects aged ≥ 65 years discontinued the study drug due to an adverse event. Conclusions: All 123 patients ≥ 65 years of age (including 14 patients ≥ 75 years of age) with HCV infection in the ASTRAL -1, -2, -3 studies achieved an SVR12. SOF/VEL was highly effective for treatment of GT1-6 chronic HCV in patients aged 65 and older and resulted in similar SVR rates and safety and tolerability profiles as compared with those < 65 years of age.

Sa1525

RVR in different categories of genotype 3 patients using Generic Sofosbuvir

Background 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.

Sa1523 SUSTAINED VIROLOGICAL RESPONSE IN HCV PATIENTS TREATED WITH DACLATASVIR+SOFOSBUVIR, WITH OR WITHOUT RIBAVIRIN: A MULTICENTER, FIELD-PRACTICE EXPERIENCE Rodolfo Sacco, Elena Salomoni, Sara Parodi, Elena Gianni, Laura Gragnani, Giovanni Andreotti, Anna Linda Zignego, Riccardo Gattai, Ilo Vivaldi, Andrea De Luca, Dario Bartolozzi, Roberta Cinelli, Marco Pozzi, Barbara Coco, Gherardo Tapete, Paolo Forte, Rachele Puntili, Liana Ricciardi, Spartaco Sani, Sauro Luchi, Maurizia Rossana Brunetto, Beatrice Valoriani, Maria Piera Riccardi, Cesira Nencioni, Donatella Aquilini, Alessandro Nerli, Francesco Esperti, Francesco Mazzotta, Silvia Fabiani, Francesco Menichetti, Giampaolo Bresci, Piero Colombatto Aim: The combination of daclatasvir (DAC) and sofosbuvir (SOF) achieved in clinical trials sustained virological response at post-treatment week 12 (SVR12) in >90% of chronicallyinfected HCV patients, with mild side effects. We evaluated the efficacy of DAC+SOF treatment, with or without ribavirin (RBV), in HCV Genotype 1, 2, 3 and 4 patients with advanced liver disease in real life clinical practice. Patients and methods: We included in the study 372 HCV patients fulfilling eligibility criteria of the Italian Drug Agency treated in 10 referral centers covering the whole region of Tuscany, Italy. Fibrosis stage was evaluated by Transient Elastometry (METAVIR F3>10kPa, F4>13 kPa). Clinical cirrhosis was defined by at least one of the following condition: decompensation, portal hypertension at the endoscopy, platelets<100,000/mmc. Patients received daily SOF+DAC treatment for 12 (104) or 24 (268) weeks, 150 (40.3%) received also RBV, according to EASL guidelines. The primary efficacy endpoint was SVR12. Results: Mean age was 58±8 years, 65.3% were males, mean body mass index was 24.7±4.0 kg/m2 and 59.5% were naïve to antiviral treatments. F4 fibrosis was present in 266 (71.5%) patients, clinical cirrhosis in 187 (50.4%). HCV genotypes distribution was: 101 G1 (27.2%), 42 G2 (11.3%), 210 G3 (56.5%) and 18 G4 (4.9%). One patient (0.3%) was HBV co-infected, 98 (29.3%) were anti-HBc positive and 44 (11.9%) were HIV-positive. At baseline, 146/369 (39.6%) showed HCV RNA ≥2×106 IU/mL. ALT mean levels were 101±73 U/L. Six (1.6%) patients dropped out (1 OLT, 1 HCC, 1 death and 3 lost to follow-up). In patients who completed treatment and followup, SVR12 was 99.2% (363/366): 100% in G1, 97.6% in G2, 97.1% in G3 and 100% in G4. Virological failures occurred in 1 G2 patient previously treated with SOF+RBV and in 2 G3 naïves, all with F4 fibrosis (2 clinical cirrhosis) and no RBV-treated. In one (HIV coinfected) G3 patient a virological breakthrough occurred at week 24 (end of treatment), whereas a relapse during follow-up was observed in the other cases. On therapy, HCV RNA declined below lower limit of quantification at week 2 in 27.3% of the patients and in 52.5% at week 4. At least 1 adverse events (AE) was reported in 170 (45.7%) patients; the most frequent AE was elevated bilirubin (26.6%), with mean maximum value of 2.19±1.48 mg/mL and grade 3 and 4 elevation in 16 (4.3%) and 1 (0.27%) patients. Anemia was the second AE reported in 18.0% of the patients, its incidence was higher in those who received RBV (22.0%) than in the others (15.3%), reaching grade 2 in 18 (4.8%), 9 RBV-treated. Conclusions: DAC+SOF combination was associated with a SVR12 of 99.2% in a heterogeneous cohort of HCV patients with advanced fibrosis. This study confirms the high efficacy and the pangenotypic action of this combination that showed high tolerability in field-practice.

Sa1526 HEPATOCELLULAR CARCINOMA SURVEILLANCE IS ESSENTIAL FOR CIRRHOTIC PATIENTS DURING AND POST DIRECT-ACTING ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C Sentia Iriana, Hirsh Trivedi, Ammu Susheela, Annie Vong, Bilal Nasir, Ning Ling, Daryl Lau, Michael Curry BACKGROUND: New direct-acting antivirals (DAA) were highly effective in the traditionally difficult to treat populations such as those with advanced hepatic fibrosis and HIV/HCV coinfection. These patients are also at high risk of developing hepatocellular carcinoma (HCC). Recent reports provided controversial results on the rates of HCC associated with DAA therapy. The aim of this study was to evaluate the features of recurrent and de novo HCC among HCV patients treated with various interferon-free DAA regimens. METHODS: This is a single, tertiary center retrospective study. Between January 2014 and July 2016, a total of 1,387 patients with chronic hepatitis C received FDA-approved DAA therapy. Among them, 47 patients were coinfected with HIV and HCV. The majority, 1078 (78%) had HCV genotype 1 and 564 (41%) had documented cirrhosis prior to antiviral therapy. RESULTS: In this cohort, 88 had history of HCC prior to DAA therapy. Seventeen (19%) experienced recurrent HCC between 2 and 11 months after initiating DAA. In addition, there were 20 de novo HCC identified; 4 during and 16 after therapy. All except one of these HCC cases occurred in the background of cirrhosis and 90% were male patients. Ten of the seventeen patients with recurrent HCC had 1 or 2 previous recurrences between 4 months and 5 years before starting therapy. Twelve (70%) of the lesions were solitary ≤3 cm at diagnosis. Among the de novo HCC, 7 (35%) and 4 (20%) were diagnosed within 6 and 12 months on treatment respectively. However, 9 (45%) were identified after 13 to 22 months on therapy. 16 (80%) of the de novo lesions were solitary and 14 were ≤3 cm at diagnosis. Interestingly, none of the HIV/HCV coinfected patients developed HCC even though 40% had at least stage 3 fibrosis. Among the 44 patients who had HCC prior to liver transplant, only 1 had HCC 4 month-post DAA therapy. CONCLUSIONS: Among HCV patients with advanced fibrosis, high HCC risk remains at least during the first 2 years of DAA therapy and require regular HCC surveillance. That is particular important among those with history of HCC prior to DAA. The characteristics of early and late-onset HCC related to the timing of DAA treatment were similar in this cohort. Patients with HIV and HCV coninfection and post liver transplant recipients with HCC prior to transplant do not appear to have increased risk of HCC on DAA therapy. Longer-term follow-up study is essential to evaluate the HCC risk after successful DAA therapy.

Sa1524 SAFETY AND EFFICACY OF SOFOSBUVIR/VELPATASVIR FOR THE TREATMENT OF CHRONIC HEPATITIS C IN PATIENTS AGED 65 YEARS OR OLDER: A RETROSPECTIVE ANALYSIS OF PHASE 3 STUDIES Mitchell L. Shiffman, Mark S. Sulkowski, Graham R. Foster, Sean Byrne, John Wolf, Chester Grabowski, John McNally, Diana Brainard, Kyle P. Etzkorn, Aasim Sheikh, Jordan J. Feld Background and Aims: The effectiveness and safety of HCV therapy in the direct acting antiviral (DAA) era among elderly patients has been under reported, specifically in GT 26. Many studies limit entry criteria to patients who are less than 65 years old. As the birth cohort of those born between 1945-1965 ("baby boomers") ages, generating HCV treatment safety and efficacy data in this population is warranted. The aim of this analysis is to retrospectively evaluate the safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) from phase 3 trials in patients aged 65 and older with HCV GT 1-6. Methods: Three phase 3 clinical trials (one placebo-controlled and two open-label), conducted in North America, Europe, Asia, Australia and New Zealand, evaluated the safety and efficacy of 12 weeks of SOF/VEL for the treatment of GT1-6 chronic HCV infection. The inclusion criteria had no upper limit to age. The primary endpoint was SVR at 12 weeks after the end of therapy (SVR12). SVR12, treatment emergent adverse events (AEs), and laboratory abnormalities were analyzed by age groups < 65 vs. ≥ 65 years. Results: Of the 1,035 subjects enrolled

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AASLD Abstracts

AASLD Abstracts

LOWER SUSTAINED VIROLOGIC RESPONSE IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED FOR HEPATITIS C WITH DIRECT ACTING ANTIVIRALS Kelvin T. Nguyen, Peter Konyn, Gina Choi, Francisco A. Durazo, Steven-Huy Han, Samantha Ramirez, Sammy Saab, Mohamed El-Kabany El-Kabany