Sofosbuvir in combination with daclatasvir in liver transplant recipients with HCV infection: A systematic review and meta-analysis.

Studies focusing on the efficacy of SOF+DCV regimen on liver transplantation recipients with HCV infection are still limited. In the current study, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and tolerability of SOF+DCV regimen, with or without ribavirin, on post-LT setting. A systematic literature search of various databases as well as abstracts of major liver diseases conferences was performed. Studies with SVR data in HCV infected liver transplantation recipients treated with daclatasvir/sofosbuvir regimen were included. All statistical analyses were conducted by R version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria). Seven studies with a total of 379 LT recipients were included in this study. Most of these LT recipients had genotype 1 HCV infection. The overall rate of SVR12 reached 93.3% (95% CI: 83.3% to 99.4%). After excluding the study of Fontana et al., the SVR12 reached 96.8% and heterogeneity was lowered down (P=0.17). In three studies, patients treated with SOF+DCV (n=146) had a higher SVR12 rate than that of patients treated with SOF+DCV+RBV (n=83) (OR 0.33, 95% CI: 0.12 to 0.87; P=0.02). There was no difference in SVR12 between patients infected with HCV genotype 1 and genotype 3 (P=0.57) and no difference was found in SVR12 rate between 12-week therapy and 24-week therapy (P=0.82). The most common adverse effects (AEs) were: anemia 32% (n=64/202), infections 26% (n=38/149), neutropenia 23% (n=35/149), thrombocytopenia 21% (n=32/149) and renal failure 8% (n=12/149). SOF+DCV±RBV regimen is of high efficacy and tolerability in LT recipients with HCV infection.

Liao H ，Tan P ，Zhu Z ，Yan X ，Huang J ... -  《-》

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study.

In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.

Lionetti R ，Calvaruso V ，Piccolo P ，Mancusi RL ，Mazzarelli C ，Fagiuoli S ，Montalbano M ，Lenci I ，Carrai P ，Guaraldi G ，Visco-Comandini U ，Milana M ，Biolato M ，Loiacono L ，Valente G ，Craxì A ，Angelico M ，D'offizi G ... -  《-》

Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison.

Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.

Swallow E ，Song J ，Yuan Y ，Kalsekar A ，Kelley C ，Peeples M ，Mu F ，Ackerman P ，Signorovitch J ... -  《-》

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

Fontana RJ ，Brown RS Jr ，Moreno-Zamora A ，Prieto M ，Joshi S ，Londoño MC ，Herzer K ，Chacko KR ，Stauber RE ，Knop V ，Jafri SM ，Castells L ，Ferenci P ，Torti C ，Durand CM ，Loiacono L ，Lionetti R ，Bahirwani R ，Weiland O ，Mubarak A ，ElSharkawy AM ，Stadler B ，Montalbano M ，Berg C ，Pellicelli AM ，Stenmark S ，Vekeman F ，Ionescu-Ittu R ，Emond B ，Reddy KR ... -  《-》

Ledipasvir + Sofosbuvir for Liver Transplant Recipients With Recurrent Hepatitis C: A Systematic Review and Meta-analysis.

Studies focusing on the efficacy and safety of ledipasvir (LDV) + sofosbuvir (SOF) therapy in liver transplant (LT) recipients with hepatitis C virus (HCV) recurrence are still limited. Therefore, the aim of our work was to perform a systematic review and meta-analysis to evaluate outcome data of LDV + SOF therapy in LT recipients. Multiple databases were systematically searched for eligible studies. We included studies reporting sustained virological response 12 weeks after treatment (SVR12) and treatment-related adverse events (AEs) in LT recipients treated with LDV + SOF ± ribavirin (RBV) for HCV recurrence. All statistical analyses were conducted by using R version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria). Twelve studies with a total of 994 LT recipients were included, most of which were diagnosed with HCV genotype 1 infection. The overall SVR12 reached 96.3% (95% confidence interval [CI]: 94.9%-97.5%) and no significant heterogeneity was observed (Q statistic = 10.63, P = .47; I2 = 0%). No difference was found in SVR12 between treatments for 12 weeks and 24 weeks (P = .18). Patients treated with LDV + SOF + RBV (n = 525) exhibited an SVR12 rate of 95.1% (95% CI 92.8%-96.6%), which showed no difference from the findings in the LDV + SOF treatment group (n = 314) with an SVR12 reaching 94.9% (95% CI 91.5%-97.0%; P = .92). There was a tendency for a higher SVR12 in patients without cirrhosis than those with cirrhosis (P < .05). The most common AEs were listed as following: anemia 41.9% (n = 203 of 484), fatigue 39.1% (n = 207 of 530), headache 24.2% (n = 128 of 530), nausea 21.9% (n = 106 of 484), and diarrhea 19.0% (n = 92 of 484). LDV + SOF-based treatment is highly effective and well tolerated in LT recipients with HCV reinfection.

Liao HT ，Tan P ，Huang JW ，Yuan KF ... -  《-》