- Email: [email protected]
Su1459 Safety of Direct Acting Antiviral Therapy in Kidney Transplant Recipients with Chronic Hepatitis C Infection
a real-time PCR system. RESULTS: If all patients received LDF/SOF, the total cost is $7535000. The cost followed by this treatment algorithm is $3816000. Fifty six of 61 (91.8%) patients who were treated by Peg-IFN+RBV+SMV were achieved to SVR and 42 of 46 (91.3%) patients who were treated by ASV/DCV were achieved to SVR. Nine patients who fail in SVR by Peg-IFN+RBV+SMV or ASV/DCV would be supposed to be retreated by LDF/SOF and 8 patients would become SVR. The cost per SVR by Peg-IFN+RBV+SMV is $23250 and those by ASV+DCV is $27000. The total cost per SVR using by this treatment algorithm is $32500 but those by LDF/SOF is $57600. Peg IFN is not attractive in the era of DAAs, but this option for easy to treat patients reduced cost. CONCLUSIONS: Although this study is not consider the effect of advert events and efforts, the algorithm with eligibility of IFN therapy and testing for SNP of IL28B and NS5A-RAVs in order to optimize therapy with Peg-IFN+RBV+SMV, ASV+DCV, and LDF/SOF appears cost-effective in chronic hepatitis C genotype 1.
reported to be 100% and the SVR12 for Harvoni in pts with and without cirrhosis have been reported to be > 95% in the respective registration trials. Aim: To determine SVR12 rates with Viekira pack & Harvoni +/-RBV for gen 1B CHC in a community based treatment cohort. Methods: Interim data from a combined treatment cohort (n=120) of four large community-based hepatology referral centers were evaluated to assess EOT response (undetectable viral load at EOT) & SVR12 rates for treatment naïve or treatment experienced gen 1B CHC pts including those with cirrhosis treated with either Viekira pack or Harvoni+/RBV at recommended package insert doses. Treatment duration for Viekira Pack +/- RBV was 12 weeks & for Harvoni +/-RBV was 8, 12, 24 weeks at the discretion of the treating hepatologist. Dosing of ribavirin was weight based. Results: Of the 120 patients in this cohort, 63% were male, 44% were Caucasians and 28% had failed prior treatment. 36/93 (39%) had cirrhosis and 95/120 (79%) were treated with Harvoni +/- RBV. Overall, 85/ 120 & 43/120 had reached EOT & SVR12 time points by Nov 30, 2015. Of those who reached EOT, 100% achieved EOT response with Viekira pack +/- RBV and Harvoni+/RBV. SVR12 was achieved in 2/2 (100%) with Viekira pack & 40/41 (98%) with Harvoni. Treatment was well-tolerated overall with no side effects reported in 52% with Harvoni & 58% with Viekira pack. In those reporting adverse events the four most common side effects with both drugs were fatigue, headache, nausea and insomnia. There were no discontinuations secondary to adverse events. Treatment was discontinued in only 1 patient treated with Viekira pack due to a significant drug-drug interaction. Conclusions: Both Harvoni and Viekira pack achieved high EOT response with minimal side effects in a community based treatment cohort of CHC gen 1B pts confirming results of the registration trials. This suggests that a combination of 2 DAA's (Harvoni) might be equally effective as 3 DAA's (Viekira pack) for treatment of gen 1b. SVR12 results to follow
The Course of Liver Injury in Patients With Concomitant Chronic Hepatitis C Infection and Autoimmune Hepatitis After Treatment With Direct Acting AntiViral Agents Jasmine Dukandar, Kristina Chacko, Clara Tow Introduction: The advent of direct acting antiviral agents (DAAs) for hepatitis C virus (HCV) enables patients with concomitant autoimmune hepatitis (AIH) to receive antiviral treatment. Prior to the development of DAAs, the backbone of HCV treatment was interferon (IFN), an antiviral agent that causes a non-specific activation of the immune system, making HCV treatment with IFN contraindicated in patients with AIH. This series describes 5 patients with chronic HCV and biopsy proven AIH who are treated with DAA therapy and achieve sustained virologic response at 12 weeks (SVR12) and biochemical remission of AIH. Methods: The medical records of five patients evaluated at a single urban, academic center with chronic HCV and biopsy proven AIH were reviewed. Results: 5 female patients with chronic hepatitis C (genotype 1 N=3, genotype 2 N=2) were diagnosed with AIH based on positive serology (anti-nuclear antibody N=5, anti-smooth muscle antibody N=1, anti-liver-kidney microsomal antibody N=1), elevated immunoglobulin G (mean =3,306) and liver biopsy. All 5 patients had histologic evidence of AIH characterized by interface hepatitis, plasma cell infiltrates and fibrosis (stage 1 N=0, stage 2 N= 3, stage 3 N=1, stage 4 N=1). Treatment with azathioprine (AZA) and budesonide was initiated in 4/5 patients without complete biochemical response. Treatment of HCV with DAA agents (sofosbuvir + ribavirin N=2, simeprevir + sofosbuvir N=2, ledipasvir + sofosbuvir N=1) was successful in all 5 patients with SVR12. 2 patients had treatment failure with IFN-based therapy. The average peak ALT prior to DAA was 415U/L (range 135-1032U/L). All patients had complete normalization of ALT after initiation of DAA (mean=3 months, range=2 weeks-13 months). 2 patients were weaned off AZA and budesonide with normal liver enzymes (mean ALT =12) more than 3 months after completing DAA therapy. 2 patients remain on AZA monotherapy more than 12 months after completing DAA therapy and have normal liver enzymes. Discussion: Previous studies have demonstrated a co-occurrence of autoimmune diseases and antinuclear antibody positivity in patients with chronic HCV. In certain cases of genetically predisposed hosts, HCV may serve as a trigger for AIH. This case series demonstrates the efficacy of DAA therapy in patients with chronic HCV who had a contraindication to IFN therapy given concomitant biopsy-proven AIH. The normalization of liver tests and the ability to withdraw immunosuppressive agents following HCV treatment suggests that the pathogenesis of AIH may be directly mediated by HCV. In this series, clearance of HCV appears to successfully treat AIH. Given the lack of long-term follow up and post-treatment liver biopsy, the risk of AIH relapse remains unknown.
Su1456 Safety and Efficacy of Ledipasvir and Sofosbuvir for Hepatitis C in a Community Setting Chandrashekhar Thukral, Joseph J. Vicari, Andrew Bernsten, Kathy Geissler, Sara Popejoy Background: The approval of ledipasvir/sofosbuvir has led to a paradigm shift in the treatment of genotype 1 Chronic Hepatitis C (CHC). Trials have shown the drug combination to be effective in treating treatment naive patients with and without cirrhosis as well as patients who failed to achieve sustained virological response (SVR) after treatment with PEGinterferon and ribavirin, with or without protease inhibitors. SVR rates of 94% to 99% were observed in these trials (1, 2, 3). The goal of our study was to evaluate the SVR in a similar cohort of patients in a large community based practice. Methods:We identified 185 patients in our practice with genotype 1 CHC who have either completed or are currently undergoing treatment with ledipasvir/sofosbuvir. We analyzed charts from 60 of the 185 patients who have completed treatment and have 12 week post treatment viral loads available. Treatment durations were 8,12, and 24 weeks depending on clinical status. Results: Of the 64 patients analyzed, 61% were male and 39% were female. Sixty-nine percent were Caucasian, 26% African American, and 5% Hispanic. Sixty-eight percent of patients were treatment naïve. Thirty-two percent had previously failed therapy with Ribavirin/interferon therapy, with or without protease inhibitor. Seventeen percent of patients were cirrhotic.Of the 13 patients who completed 8 weeks of therapy, 85% achieved SVR. Of the 44 who completed 12 or 24 weeks of therapy, 100% achieved SVR. Eleven percent of patients were non-compliant or lost in follow-up. Dropout rate due to side effects was less than 1%. Most common side effects were headache and fatigue. Overall SVR rate including those lost to follow-up was 86%. SVR rate for patients that completed therapy and were accounted for was 96%. The SVR in cirrhotics and those previously treated was 100%. Discussion: Our data show that SVR for genotype 1 CHC patients treated with ledipasvir/sofosbuvir are high. The SVR rate in the 8-week treatment group was lower than that observed in the larger trials. We believe that this is due to a small sample size in our study. Conversely the 100% SVR rates in the other two treatment groups (12 weeks and 24 weeks) was slightly higher than that observed in the clinical trials. As we collect more data, we predict that SVR rates in a community setting will mirror those seen in large clinical trials. Our analysis also confirms that this drug was well tolerated by the majority of patients with minimal side effects. 1. Afdhal N, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 15:370 (20):1889-98. 2. Afdhal N, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 17:370 (16):1483-93. 3. Kowdley KV,et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 15:370 (20): 1879
Su1459 Safety of Direct Acting Antiviral Therapy in Kidney Transplant Recipients with Chronic Hepatitis C Infection Hani El-Halawany, Kamran Qureshi Background: The worldwide prevalence of chronic hepatitis C infection (HCV) is 2.4 % and is the leading cause of liver disease after Kidney Transplant (KT). HCV positive (+ve) KT recipients have worse overall and graft survival compared with HCV negative KT recipients. Treatment of HCV before KT with interferon (IFN) based therapies showed poor tolerability. IFN use is relatively contraindicated after KT due to increased risk of allograft rejection and organ failure. Because of the anticipated reduced toxicities, the new Direct Acting Antivirals (DAA) could be used in KT recepients. Methods: 20 HCV +ve KT recipients were prospectively enrolled in the study at the time of initiation of DAA. We report the data of 15 recipients who have started or completed HCV therapy with DAA medications. Safety parameters including renal function and liver function testing for evidence of worsening graft function were monitored. Results: 15 adult (Mean age 58.5 years; Male:Female = 8:3) KT recipients have been started on therapy ranging from 1 year post transplant and above. 8 received HCV +ve grafts. 14 of the patients were genotype 1 and 1 patient was genotype 2a. 2 completed Sofosbuvir 400mg and Simeprevir 150mg daily combination, 11 were treated with Sofosbuvir/Ledipasvir 150mg/90mg daily for 12 weeks and 1 completed Sofosbuvir 150mg plus Ribavirin therapy. There were no episodes of graft rejection and none required modification in immunosuppression. None of the patients experienced any adverse events requiring cessation of therapy. One patient had anemia related to ribavirin and
Su1457 Are 3 DAA's Better Than 2 DAA's for the Treatment of Chronic Hepatitis C Genotype 1B? John E. Hermann, Janet Gripshover, Zachary Harris, Andres Duarte-Rojo, Manjushree Gautam, Jena Mann, Stevan Gonzalez, Mohammad Ashfaq, Darryn Potosky, Apurva A. Modi Background: There are currently two commonly used FDA approved treatment options for chronic hepatitis C (CHC) genotype 1B which include (1) Viekira pack (Ombitasvir + Dasabuvir + Paritaprevir/Ritonavir) +/- Ribavirin (RBV) for 12 weeks and (2) Harvoni (Sofosbuvir + Ledipasvir) +/- RBV for 8-24 weeks. Viekira pack is a combination of 3 DAA's, which includes a protease inhibitor, NS5B polymerase inhibitor and NS5A inhibitor. Harvoni is a combination of 2 DAA's, which includes NS5B polymerase inhibitor and NS5A inhibitor The SVR12 rates for Viekira pack +/- RBV in pts with and without cirrhosis have been
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3 with 22 %1. Interferon therapy because of its side effects and failure rates is of great concern. With the advent of sofosbuvir and the results documented so far, there is a hope in effectively curing the disease, but most of the literature is regarding Genotype 1. Materials and Methods: This open-label, non-randomized, uncontrolled study is carried out at Center for Liver and Digestive Diseases, Holyfamily Hospital, Rawalpindi. We enrolled patients from September 2014 through June 2015 who are 18 years or older and have chronic infection with HCV genotype 3, with HCV RNA levels detectable by PCR regardless of whether they are treatment naïve or have experienced Interferon in the past. The patients are offered sofosbuvir 400mg once daily along with ribavirin for a period of 24 weeks. All those patients are included in the study that has followed up with at least 1 PCR during the treatment course. Results: A total of 198 patients are enrolled in the study having genotype 3 amongst which 82 are females and 116 are males. 37% are treatment naïve, 36% are relapsers and 27% are non-responders. 39(20%) were having decompensated cirrhosis. A data of 59 patients with follow-up PCR as early as 1 week is available. 46(80%) out of them become PCR negative at 1st week of treatment showing a very rapid virological response(VRVR). Rapid virological response (RVR) in treatment naïve patients is 94.6%, in relapsers 91.4% and in non-responders 88% respectively. A cumulative RVR of 89.2% is achieved. Amongst the patients with decompensated cirrhosis the RVR is 90.6%.(Fig 1) Conclusion: Sofosbuvir has been showing promising results so far in Genotype 3 patients with 89.2% eradicating the virus at 4 week treatment and 80% eradicating it as early as 1st week of treatment. The results are equally good for patients with decompensated cirrhosis. References: 1. Gower E, Estes C, Blach S, Shearer KR, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014 vol. 61 j S45-S57
required dose adjustment with resolution of his anemia. All KT recipients had either stable or improved creatinine during treatment of their HCV. There was overall improvement in mean white blood cell count, hemoglobin, platelet count, total bilirubin, AST, ALT and albumin in all of the patients treated. 5 patients who received HCV +ve donor kidneys achieved sustained viral response (SVR) 12. 5 patients who received HCV -ve donor kidneys achieved SVR 12. Conclusion: In our cohort of KT recipients, DAAs showed an excellent safety profile without any significant adverse events including worsening renal function or graft rejection. We believe the new generation of DAA are safe and well tolerated in KT recipients and can improve overall graft survivability in this subset of patients.
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Age No Bar With New Anti-HCV Directly Acting Anti-Viral Agents: Real World Experience at a Single Tertiary Care Center in Rural Pennsylvania Amir N. Rezk, Julia Leddy, Erin M. Ulrich, Waseem Butt, Chuan L. Miao, Nina Ahuja, Harshit S. Khara, Robert Smith, Nihar Shah Introduction: Hepatitis C virus (HCV) is a leading cause of chronic liver disease and is disproportionately higher in older patients, underscoring the need for their treatment. The advent of directly acting anti-viral agents (DAA) expanded the pool of treatment candidates and increased the rate of virus eradication. However, data on HCV treatment with DAA and its effectiveness in elderly HCV patients is limited. Since elderly patients are more likely to have advanced liver disease, increased duration of infection and rate of disease progression, they are in special need of effective therapy. The following cases represent instances in which age should not be viewed as a contraindication but rather an opportunity to achieve a cure. Aim: To retrospectively evaluate the safety, efficacy and tolerability of newer DAA among HCV elderly patients (‡ 70 years old). Methods: Medical records of patients ‡ 70 years old who initiated HCV treatment between December 2013 and July 2015 in the Hepatology clinic at our tertiary medical center were reviewed and data collected. We collected data regarding demographic information, HCV genotype, presence or absence of cirrhosis, history of prior treatment, DAA treatment regimen and duration, treatment outcomes and side effects. Results: Ten patients were found to be ‡ 70 years old, with a mean age of 75 years (range 70 to 90) (Table 1). Data analysis showed that 80% had genotype 1, 60% had compensated cirrhosis while the rest were non-cirrhotic and 60% were treatment naïve. All 10 patients completed treatment. Treatment outcomes showed that 70% achieved RVR (rapid viral response), 100% achieved EOTR (end of treatment response) and 9 out of those 10 patients (90%) achieved SVR12 (sustained virologic response at 12 weeks). One patient is awaiting to check her SVR12 labs in January 2016. Reported side effects were asymptomatic anemia in 2 patients that improved with completion of therapy; one of which required RBV dose reduction. One patient had symptomatic anemia requiring discontinuation of RBV and blood transfusion. Conclusion: Age is not a limitation for HCV treatment with DAA and elderly population can no longer be considered as difficult to treat subgroup. As noted in clinical trials, cure from HCV infection can be achieved in the elderly population effectively and safely in majority of patients in real world. Sofosbuvir based regimen appears to achieve promising results in elderly patients.
Su1462 US Experience of Sofosbuvir + Ledipasvir + Ribavirin for 12 Weeks in Previous Treatment Experienced Genotype 1 Chronic Hepatitis C With Cirrhosis John E. Hermann, Stevan Gonzalez, Manjushree Gautam, Mohammad Ashfaq, Apurva A. Modi Background: The SIRIUS French trial was a randomized double blinded placebo controlled trial that showed that treatment with Ledipasvir + Sofosbuvir (L+S) with RBV for 12 weeks was equally efficacious as L+ S for 24 weeks with SVR12 rates of 96% and 97% respectively in previously treatment experienced compensated cirrhotic patients to Interferon based regimens including triple therapy with protease inhibitors (Bocepravir or Telaprevir) The current FDA recommendation is to use L+ S for 24 weeks in such patients based on the results of ION-2 trial. Aim: To evaluate the efficacy of single tablet regimen of L + S with ribavirin for 12 weeks in CHC genotype 1 previous treatment experienced cirrhotics in a community based treatment cohort. Methods: Interim data from a cohort (n=27) were evaluated to assess EOT response (undetectable viral load at EOT) & SVR12 rates for patients with chronic hepatitis C gen 1 with cirrhosis previous treatment experienced. Treatment duration for Harvoni + RBV was 12 weeks and dosing of ribavirin was weight based. Results: Of the 27 patients in this cohort, 22 (82%) were male, 22 (82%) were gen 1a, 12 (45%) were decompensated cirrhotics, 15 (56%) were treatment experienced with IFN/Peg-IFN +/- RBV, 5 (19%) were treatment experienced with triple therapy, and 12 (44%) were treatment experienced with Sim + Sof. There were 8 patients with greater than 1 previous treatment (29.6%). Of the 27 patients, 100% achieved EOT response. 14/15 patients achieved SVR 12 (93 %), and 12 have not reached the SVR 12 time point as of November 30, 2015. 6 patients had no side effects on treatment (22%), and 5 patients were hospitalized during treatment (19%). The most common side effects to treatment were fatigue, headache, insomnia, dizziness, and shortness of breath. There is a 0% discontinuation rate of treatment, however 7% of patients had ribavirin decreased due to anemia, and were hospitalized, although they did not stop treatment. Conclusion: Harvoni with Ribavirin for 12 weeks is equally efficacious as Harvoni for 24 weeks for CHC gen 1 treatment experienced patients with cirrhosis in a US community based treatment cohort confirming the results of the SIRIUS trial.
Table 1. Patients ‡ 70 years old who initiated HCV treatment with DAA between December 2013 and July 2015. IFN= Interferon. RBV= Ribavirin. RVR= rapid viral response. EOTR= end of treatment response. SVR12= sustained virologic response at 12 weeks.
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A Single Center Experience With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With and Without Ribovirin for Treating Hepatitis C Virus Genotype 1 Infection in Patients With and Without Cirrhosis Dmitriy O. Khodorskiy, James S. Park
Trends of Sofosbuvir Treatment for Chronic Hepatitis C Infection in Genotype 3 Patients—An Experience From Pakistan Tayyab S. Akhter, Muhammad Umar, Shifa Umar, Gul Nisar, Hamama-tul-Bushra Khaar, Arsalan Shehzad, Aqsa Naseer, Sadia Ahmad, Zahid Minhas, Javaria Z. Khan, Muhammad I. Rasheed
Background: The real world experience of Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir (3D regimen) in the treatment of chronic hepatitis C virus (HCV) genotype 1 (GT1) infection is not well known. The clinical experience of the 3D regimen administered in a single academic center was evaluated. The aim of the study was to determine the efficacy and safety of the 3D regimen for treating HCV GT1 infection in patients with and without
Abstract: Introduction: The global prevalence of Anti HCV is estimated to be about 1.6% with a viraemic prevalence of about 1.1% roughly accounting 80 million worldwide population. Genotype 1 has got the highest global distribution of about 46% followed by Genotype
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reported to be 100% and the SVR12 for Harvoni in pts with and without cirrhosis have been reported to be > 95% in the respective registration trials. Aim: To determine SVR12 rates with Viekira pack & Harvoni +/-RBV for gen 1B CHC in a community based treatment cohort. Methods: Interim data from a combined treatment cohort (n=120) of four large community-based hepatology referral centers were evaluated to assess EOT response (undetectable viral load at EOT) & SVR12 rates for treatment naïve or treatment experienced gen 1B CHC pts including those with cirrhosis treated with either Viekira pack or Harvoni+/RBV at recommended package insert doses. Treatment duration for Viekira Pack +/- RBV was 12 weeks & for Harvoni +/-RBV was 8, 12, 24 weeks at the discretion of the treating hepatologist. Dosing of ribavirin was weight based. Results: Of the 120 patients in this cohort, 63% were male, 44% were Caucasians and 28% had failed prior treatment. 36/93 (39%) had cirrhosis and 95/120 (79%) were treated with Harvoni +/- RBV. Overall, 85/ 120 & 43/120 had reached EOT & SVR12 time points by Nov 30, 2015. Of those who reached EOT, 100% achieved EOT response with Viekira pack +/- RBV and Harvoni+/RBV. SVR12 was achieved in 2/2 (100%) with Viekira pack & 40/41 (98%) with Harvoni. Treatment was well-tolerated overall with no side effects reported in 52% with Harvoni & 58% with Viekira pack. In those reporting adverse events the four most common side effects with both drugs were fatigue, headache, nausea and insomnia. There were no discontinuations secondary to adverse events. Treatment was discontinued in only 1 patient treated with Viekira pack due to a significant drug-drug interaction. Conclusions: Both Harvoni and Viekira pack achieved high EOT response with minimal side effects in a community based treatment cohort of CHC gen 1B pts confirming results of the registration trials. This suggests that a combination of 2 DAA's (Harvoni) might be equally effective as 3 DAA's (Viekira pack) for treatment of gen 1b. SVR12 results to follow
The Course of Liver Injury in Patients With Concomitant Chronic Hepatitis C Infection and Autoimmune Hepatitis After Treatment With Direct Acting AntiViral Agents Jasmine Dukandar, Kristina Chacko, Clara Tow Introduction: The advent of direct acting antiviral agents (DAAs) for hepatitis C virus (HCV) enables patients with concomitant autoimmune hepatitis (AIH) to receive antiviral treatment. Prior to the development of DAAs, the backbone of HCV treatment was interferon (IFN), an antiviral agent that causes a non-specific activation of the immune system, making HCV treatment with IFN contraindicated in patients with AIH. This series describes 5 patients with chronic HCV and biopsy proven AIH who are treated with DAA therapy and achieve sustained virologic response at 12 weeks (SVR12) and biochemical remission of AIH. Methods: The medical records of five patients evaluated at a single urban, academic center with chronic HCV and biopsy proven AIH were reviewed. Results: 5 female patients with chronic hepatitis C (genotype 1 N=3, genotype 2 N=2) were diagnosed with AIH based on positive serology (anti-nuclear antibody N=5, anti-smooth muscle antibody N=1, anti-liver-kidney microsomal antibody N=1), elevated immunoglobulin G (mean =3,306) and liver biopsy. All 5 patients had histologic evidence of AIH characterized by interface hepatitis, plasma cell infiltrates and fibrosis (stage 1 N=0, stage 2 N= 3, stage 3 N=1, stage 4 N=1). Treatment with azathioprine (AZA) and budesonide was initiated in 4/5 patients without complete biochemical response. Treatment of HCV with DAA agents (sofosbuvir + ribavirin N=2, simeprevir + sofosbuvir N=2, ledipasvir + sofosbuvir N=1) was successful in all 5 patients with SVR12. 2 patients had treatment failure with IFN-based therapy. The average peak ALT prior to DAA was 415U/L (range 135-1032U/L). All patients had complete normalization of ALT after initiation of DAA (mean=3 months, range=2 weeks-13 months). 2 patients were weaned off AZA and budesonide with normal liver enzymes (mean ALT =12) more than 3 months after completing DAA therapy. 2 patients remain on AZA monotherapy more than 12 months after completing DAA therapy and have normal liver enzymes. Discussion: Previous studies have demonstrated a co-occurrence of autoimmune diseases and antinuclear antibody positivity in patients with chronic HCV. In certain cases of genetically predisposed hosts, HCV may serve as a trigger for AIH. This case series demonstrates the efficacy of DAA therapy in patients with chronic HCV who had a contraindication to IFN therapy given concomitant biopsy-proven AIH. The normalization of liver tests and the ability to withdraw immunosuppressive agents following HCV treatment suggests that the pathogenesis of AIH may be directly mediated by HCV. In this series, clearance of HCV appears to successfully treat AIH. Given the lack of long-term follow up and post-treatment liver biopsy, the risk of AIH relapse remains unknown.
Su1456 Safety and Efficacy of Ledipasvir and Sofosbuvir for Hepatitis C in a Community Setting Chandrashekhar Thukral, Joseph J. Vicari, Andrew Bernsten, Kathy Geissler, Sara Popejoy Background: The approval of ledipasvir/sofosbuvir has led to a paradigm shift in the treatment of genotype 1 Chronic Hepatitis C (CHC). Trials have shown the drug combination to be effective in treating treatment naive patients with and without cirrhosis as well as patients who failed to achieve sustained virological response (SVR) after treatment with PEGinterferon and ribavirin, with or without protease inhibitors. SVR rates of 94% to 99% were observed in these trials (1, 2, 3). The goal of our study was to evaluate the SVR in a similar cohort of patients in a large community based practice. Methods:We identified 185 patients in our practice with genotype 1 CHC who have either completed or are currently undergoing treatment with ledipasvir/sofosbuvir. We analyzed charts from 60 of the 185 patients who have completed treatment and have 12 week post treatment viral loads available. Treatment durations were 8,12, and 24 weeks depending on clinical status. Results: Of the 64 patients analyzed, 61% were male and 39% were female. Sixty-nine percent were Caucasian, 26% African American, and 5% Hispanic. Sixty-eight percent of patients were treatment naïve. Thirty-two percent had previously failed therapy with Ribavirin/interferon therapy, with or without protease inhibitor. Seventeen percent of patients were cirrhotic.Of the 13 patients who completed 8 weeks of therapy, 85% achieved SVR. Of the 44 who completed 12 or 24 weeks of therapy, 100% achieved SVR. Eleven percent of patients were non-compliant or lost in follow-up. Dropout rate due to side effects was less than 1%. Most common side effects were headache and fatigue. Overall SVR rate including those lost to follow-up was 86%. SVR rate for patients that completed therapy and were accounted for was 96%. The SVR in cirrhotics and those previously treated was 100%. Discussion: Our data show that SVR for genotype 1 CHC patients treated with ledipasvir/sofosbuvir are high. The SVR rate in the 8-week treatment group was lower than that observed in the larger trials. We believe that this is due to a small sample size in our study. Conversely the 100% SVR rates in the other two treatment groups (12 weeks and 24 weeks) was slightly higher than that observed in the clinical trials. As we collect more data, we predict that SVR rates in a community setting will mirror those seen in large clinical trials. Our analysis also confirms that this drug was well tolerated by the majority of patients with minimal side effects. 1. Afdhal N, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 15:370 (20):1889-98. 2. Afdhal N, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 17:370 (16):1483-93. 3. Kowdley KV,et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 15:370 (20): 1879
Su1459 Safety of Direct Acting Antiviral Therapy in Kidney Transplant Recipients with Chronic Hepatitis C Infection Hani El-Halawany, Kamran Qureshi Background: The worldwide prevalence of chronic hepatitis C infection (HCV) is 2.4 % and is the leading cause of liver disease after Kidney Transplant (KT). HCV positive (+ve) KT recipients have worse overall and graft survival compared with HCV negative KT recipients. Treatment of HCV before KT with interferon (IFN) based therapies showed poor tolerability. IFN use is relatively contraindicated after KT due to increased risk of allograft rejection and organ failure. Because of the anticipated reduced toxicities, the new Direct Acting Antivirals (DAA) could be used in KT recepients. Methods: 20 HCV +ve KT recipients were prospectively enrolled in the study at the time of initiation of DAA. We report the data of 15 recipients who have started or completed HCV therapy with DAA medications. Safety parameters including renal function and liver function testing for evidence of worsening graft function were monitored. Results: 15 adult (Mean age 58.5 years; Male:Female = 8:3) KT recipients have been started on therapy ranging from 1 year post transplant and above. 8 received HCV +ve grafts. 14 of the patients were genotype 1 and 1 patient was genotype 2a. 2 completed Sofosbuvir 400mg and Simeprevir 150mg daily combination, 11 were treated with Sofosbuvir/Ledipasvir 150mg/90mg daily for 12 weeks and 1 completed Sofosbuvir 150mg plus Ribavirin therapy. There were no episodes of graft rejection and none required modification in immunosuppression. None of the patients experienced any adverse events requiring cessation of therapy. One patient had anemia related to ribavirin and
Su1457 Are 3 DAA's Better Than 2 DAA's for the Treatment of Chronic Hepatitis C Genotype 1B? John E. Hermann, Janet Gripshover, Zachary Harris, Andres Duarte-Rojo, Manjushree Gautam, Jena Mann, Stevan Gonzalez, Mohammad Ashfaq, Darryn Potosky, Apurva A. Modi Background: There are currently two commonly used FDA approved treatment options for chronic hepatitis C (CHC) genotype 1B which include (1) Viekira pack (Ombitasvir + Dasabuvir + Paritaprevir/Ritonavir) +/- Ribavirin (RBV) for 12 weeks and (2) Harvoni (Sofosbuvir + Ledipasvir) +/- RBV for 8-24 weeks. Viekira pack is a combination of 3 DAA's, which includes a protease inhibitor, NS5B polymerase inhibitor and NS5A inhibitor. Harvoni is a combination of 2 DAA's, which includes NS5B polymerase inhibitor and NS5A inhibitor The SVR12 rates for Viekira pack +/- RBV in pts with and without cirrhosis have been
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3 with 22 %1. Interferon therapy because of its side effects and failure rates is of great concern. With the advent of sofosbuvir and the results documented so far, there is a hope in effectively curing the disease, but most of the literature is regarding Genotype 1. Materials and Methods: This open-label, non-randomized, uncontrolled study is carried out at Center for Liver and Digestive Diseases, Holyfamily Hospital, Rawalpindi. We enrolled patients from September 2014 through June 2015 who are 18 years or older and have chronic infection with HCV genotype 3, with HCV RNA levels detectable by PCR regardless of whether they are treatment naïve or have experienced Interferon in the past. The patients are offered sofosbuvir 400mg once daily along with ribavirin for a period of 24 weeks. All those patients are included in the study that has followed up with at least 1 PCR during the treatment course. Results: A total of 198 patients are enrolled in the study having genotype 3 amongst which 82 are females and 116 are males. 37% are treatment naïve, 36% are relapsers and 27% are non-responders. 39(20%) were having decompensated cirrhosis. A data of 59 patients with follow-up PCR as early as 1 week is available. 46(80%) out of them become PCR negative at 1st week of treatment showing a very rapid virological response(VRVR). Rapid virological response (RVR) in treatment naïve patients is 94.6%, in relapsers 91.4% and in non-responders 88% respectively. A cumulative RVR of 89.2% is achieved. Amongst the patients with decompensated cirrhosis the RVR is 90.6%.(Fig 1) Conclusion: Sofosbuvir has been showing promising results so far in Genotype 3 patients with 89.2% eradicating the virus at 4 week treatment and 80% eradicating it as early as 1st week of treatment. The results are equally good for patients with decompensated cirrhosis. References: 1. Gower E, Estes C, Blach S, Shearer KR, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014 vol. 61 j S45-S57
required dose adjustment with resolution of his anemia. All KT recipients had either stable or improved creatinine during treatment of their HCV. There was overall improvement in mean white blood cell count, hemoglobin, platelet count, total bilirubin, AST, ALT and albumin in all of the patients treated. 5 patients who received HCV +ve donor kidneys achieved sustained viral response (SVR) 12. 5 patients who received HCV -ve donor kidneys achieved SVR 12. Conclusion: In our cohort of KT recipients, DAAs showed an excellent safety profile without any significant adverse events including worsening renal function or graft rejection. We believe the new generation of DAA are safe and well tolerated in KT recipients and can improve overall graft survivability in this subset of patients.
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AASLD Abstracts
Age No Bar With New Anti-HCV Directly Acting Anti-Viral Agents: Real World Experience at a Single Tertiary Care Center in Rural Pennsylvania Amir N. Rezk, Julia Leddy, Erin M. Ulrich, Waseem Butt, Chuan L. Miao, Nina Ahuja, Harshit S. Khara, Robert Smith, Nihar Shah Introduction: Hepatitis C virus (HCV) is a leading cause of chronic liver disease and is disproportionately higher in older patients, underscoring the need for their treatment. The advent of directly acting anti-viral agents (DAA) expanded the pool of treatment candidates and increased the rate of virus eradication. However, data on HCV treatment with DAA and its effectiveness in elderly HCV patients is limited. Since elderly patients are more likely to have advanced liver disease, increased duration of infection and rate of disease progression, they are in special need of effective therapy. The following cases represent instances in which age should not be viewed as a contraindication but rather an opportunity to achieve a cure. Aim: To retrospectively evaluate the safety, efficacy and tolerability of newer DAA among HCV elderly patients (‡ 70 years old). Methods: Medical records of patients ‡ 70 years old who initiated HCV treatment between December 2013 and July 2015 in the Hepatology clinic at our tertiary medical center were reviewed and data collected. We collected data regarding demographic information, HCV genotype, presence or absence of cirrhosis, history of prior treatment, DAA treatment regimen and duration, treatment outcomes and side effects. Results: Ten patients were found to be ‡ 70 years old, with a mean age of 75 years (range 70 to 90) (Table 1). Data analysis showed that 80% had genotype 1, 60% had compensated cirrhosis while the rest were non-cirrhotic and 60% were treatment naïve. All 10 patients completed treatment. Treatment outcomes showed that 70% achieved RVR (rapid viral response), 100% achieved EOTR (end of treatment response) and 9 out of those 10 patients (90%) achieved SVR12 (sustained virologic response at 12 weeks). One patient is awaiting to check her SVR12 labs in January 2016. Reported side effects were asymptomatic anemia in 2 patients that improved with completion of therapy; one of which required RBV dose reduction. One patient had symptomatic anemia requiring discontinuation of RBV and blood transfusion. Conclusion: Age is not a limitation for HCV treatment with DAA and elderly population can no longer be considered as difficult to treat subgroup. As noted in clinical trials, cure from HCV infection can be achieved in the elderly population effectively and safely in majority of patients in real world. Sofosbuvir based regimen appears to achieve promising results in elderly patients.
Su1462 US Experience of Sofosbuvir + Ledipasvir + Ribavirin for 12 Weeks in Previous Treatment Experienced Genotype 1 Chronic Hepatitis C With Cirrhosis John E. Hermann, Stevan Gonzalez, Manjushree Gautam, Mohammad Ashfaq, Apurva A. Modi Background: The SIRIUS French trial was a randomized double blinded placebo controlled trial that showed that treatment with Ledipasvir + Sofosbuvir (L+S) with RBV for 12 weeks was equally efficacious as L+ S for 24 weeks with SVR12 rates of 96% and 97% respectively in previously treatment experienced compensated cirrhotic patients to Interferon based regimens including triple therapy with protease inhibitors (Bocepravir or Telaprevir) The current FDA recommendation is to use L+ S for 24 weeks in such patients based on the results of ION-2 trial. Aim: To evaluate the efficacy of single tablet regimen of L + S with ribavirin for 12 weeks in CHC genotype 1 previous treatment experienced cirrhotics in a community based treatment cohort. Methods: Interim data from a cohort (n=27) were evaluated to assess EOT response (undetectable viral load at EOT) & SVR12 rates for patients with chronic hepatitis C gen 1 with cirrhosis previous treatment experienced. Treatment duration for Harvoni + RBV was 12 weeks and dosing of ribavirin was weight based. Results: Of the 27 patients in this cohort, 22 (82%) were male, 22 (82%) were gen 1a, 12 (45%) were decompensated cirrhotics, 15 (56%) were treatment experienced with IFN/Peg-IFN +/- RBV, 5 (19%) were treatment experienced with triple therapy, and 12 (44%) were treatment experienced with Sim + Sof. There were 8 patients with greater than 1 previous treatment (29.6%). Of the 27 patients, 100% achieved EOT response. 14/15 patients achieved SVR 12 (93 %), and 12 have not reached the SVR 12 time point as of November 30, 2015. 6 patients had no side effects on treatment (22%), and 5 patients were hospitalized during treatment (19%). The most common side effects to treatment were fatigue, headache, insomnia, dizziness, and shortness of breath. There is a 0% discontinuation rate of treatment, however 7% of patients had ribavirin decreased due to anemia, and were hospitalized, although they did not stop treatment. Conclusion: Harvoni with Ribavirin for 12 weeks is equally efficacious as Harvoni for 24 weeks for CHC gen 1 treatment experienced patients with cirrhosis in a US community based treatment cohort confirming the results of the SIRIUS trial.
Table 1. Patients ‡ 70 years old who initiated HCV treatment with DAA between December 2013 and July 2015. IFN= Interferon. RBV= Ribavirin. RVR= rapid viral response. EOTR= end of treatment response. SVR12= sustained virologic response at 12 weeks.
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A Single Center Experience With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With and Without Ribovirin for Treating Hepatitis C Virus Genotype 1 Infection in Patients With and Without Cirrhosis Dmitriy O. Khodorskiy, James S. Park
Trends of Sofosbuvir Treatment for Chronic Hepatitis C Infection in Genotype 3 Patients—An Experience From Pakistan Tayyab S. Akhter, Muhammad Umar, Shifa Umar, Gul Nisar, Hamama-tul-Bushra Khaar, Arsalan Shehzad, Aqsa Naseer, Sadia Ahmad, Zahid Minhas, Javaria Z. Khan, Muhammad I. Rasheed
Background: The real world experience of Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir (3D regimen) in the treatment of chronic hepatitis C virus (HCV) genotype 1 (GT1) infection is not well known. The clinical experience of the 3D regimen administered in a single academic center was evaluated. The aim of the study was to determine the efficacy and safety of the 3D regimen for treating HCV GT1 infection in patients with and without
Abstract: Introduction: The global prevalence of Anti HCV is estimated to be about 1.6% with a viraemic prevalence of about 1.1% roughly accounting 80 million worldwide population. Genotype 1 has got the highest global distribution of about 46% followed by Genotype
AASLD Abstracts
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