Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in Immunosuppressant Use.

Background and aimsAll-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).MethodsWe compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents.ResultsWe identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.ConclusionsImmunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection

Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin

Accessibility to Oral Antiviral Therapy for Patients with Chronic Hepatitis C in the United States

Abstract Background: Hepatitis C (HCV) direct acting antiviral agents (DAAs) are safe, effective, and tolerable. Most contraindications to interferon-based treatment are no long applicable. The aims of this study were to understand the predictors of approval to drug accessibility. Methods: We studied all consecutive patients with HCV prescribed DAAs between October 2014 and July 2015. Data on demographic, socioeconomic status, comorbidities, baseline laboratory values, and assessment of liver disease severity, insurance, and specialty pharmacy type were collected. Multivariate analyses were performed to identify predictors of prescription approval. Results: In total, 410 patients were prescribed DAAs between October 2014 and July 2015. Of those, 332 (81%) patients were insurance approved for therapy. Of the 332 patients accepted, 251 were accepted after the first prescription attempt, and 38 were accepted after the second and third attempts. The number of attempts for the other 43 approved patients was unknown. Older age (p = 0.001), employment (p = 0.001), lack of comorbidities (p = 0.02), liver transplantation (p = 0.018), and advanced liver disease (p =0.001) were more likely associated with obtaining approval. Household income was not associated with insurance approval. In the multivariate analysis, Medicare insurance (odds ratio [OR]) 2.67, 95% confidence interval , lack of nonliver comorbidities (OR 2.72,, and the presence of advanced liver disease (OR 1.82, 95% CI 1.04-3.24) independently predicted drug approval. Conclusion: Despite the availability of DAAs for HCV, barriers from insurance carriers continue to impair widespread use. Patients with advanced liver disease, Medicare, and without comorbidities are most likely to be insurance approved for DAAs

Boceprevir in liver transplant recipients

Background: There has been increasing interest in using protease inhibitors with pegylated interferon and ribavirin to treat recurrent hepatitis C (HCV) disease in liver transplant recipients. Methods: We retrospectively evaluated the safety and efficacy in liver transplant recipients treated for recurrent hepatitis C genotype 1 with the combination of peginterferon, ribavirin and boceprevir. Results: Twenty liver transplant recipients were treated for recurrent hepatitis C. Baseline alanine aminotransferase, total bilirubin and HCV RNA values (± SD) were 67.5 (±50.9) mg/dl, 1.78 (±1.99) U/L, and 16 955 510 (±21 620 675) IU/ml. Anaemia was a common adverse event requiring epoetin in 16 of 20 recipients and ribavirin dose reductions in 17 of 20 recipients. One-third of recipients required a blood transfusion. Filgrastim was used in 11 of 20 patients (55%) and eltrombopag in two of 20 recipients (10%) over the course of treatment. Serum creatinine level increased significantly from a baseline value of 1.33 mg/dl to 1.59 mg/dl at week 20 of boceprevir (P \u3c 0.005). The overall sustained viral response (SVR) was 50%. Of the 14 patients who had a viral load less than 1000 IU/ml at week 4 of boceprevir, the SVR was 71%. The SVR was 83% of the 11 patients who had undetectable viral levels at week 4 of boceprevir. Conclusions: Antiviral therapy utilizing boceprevir in liver transplant recipients requires close monitoring. Anaemia and neutropenia were common requiring growth factors in most recipients. On-treatment viral responses appear promising but long-term data are needed

Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis.

BackgroundFibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients.MethodsWe matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin.ResultsBaseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors.ConclusionOur results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients

Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis.

BackgroundFibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients.MethodsWe matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin.ResultsBaseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors.ConclusionOur results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients

Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin