Case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis C after liver retransplantation

A recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) can lead to accelerated allograft injury and fibrosis. The aim of this article is to report the first ever use of daclatasvir (DCV; also known as BMS‐790052), a potent orally administered nonstructural 5A replication complex inhibitor, in combination with peginterferon α (PEG‐IFNα) and ribavirin in an LT recipient. A 49‐year‐old female developed a severe recurrent HCV genotype 1b infection 4 months after transplantation with severe cholestasis on biopsy, an HCV RNA level of 10,000,000 IU/mL, an alkaline phosphatase level of 1525 IU/mL, and a total bilirubin level of 8.4 mg/dL. Despite partial virological suppression with PEG‐IFNα and ribavirin, progressive allograft failure ensued and culminated in retransplantation at 9 months. Three months after the second transplant, DCV (20 mg/day), PEG‐IFNα2a (180 μg/week), and ribavirin (800 mg/day) were prescribed for early recurrent cholestatic HCV. Serum HCV RNA became undetectable at week 3 of treatment and remained undetectable during 24 weeks of triple therapy and during the posttreatment follow‐up. DCV was well tolerated, and the trough drug levels were within the targeted range throughout the treatment. The cyclosporine trough levels were also stable during and after therapy. In conclusion, the lack of anticipated drug‐drug interactions between DCV and calcineurin inhibitors and the potent antiviral efficacy of DCV make this agent (in combination with PEG‐IFN and ribavirin) an attractive antiviral regimen worthy of further study in LT recipients with recurrent HCV. Liver Transpl, 2012. © 2012 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93517/1/23482_ftp.pd

Systematic Review: antiviral therapy of recurrent hepatitis C post liver transplant

International audienceBackground Hepatitis C viral infection is the first cause of liver transplantation worldwide. Recurrence of infection is constant and compromises patient and graft survival. Aim To provide an updated review of the main treatments of recurrent HCV. Methods MEDLINE (1990 to August 2010) and national meeting abstract search. Search terms included hepatitis C, liver transplantation, treatment. An emphasis was placed on randomized trials. Results Antiviral therapy based on pegylated interferon and ribavirin must be considered before liver transplantation but is poorly tolerated and has poor results in patients with cirrhosis and end-stage liver disease. Antiviral therapy can be administrated systematically early after liver transplantation, or in patients with established recurrent chronic hepatitis. Combination of pegylated interferon alfa plus ribavirin results in a sustained virological response of up to 30% in patients. Small trial of polyclonal anti-HCV to prevent recurrence were disappointing. Perspective Currently available antiviral therapy is effective in a minority of transplanted patients infected with HCV. Specifically targeted antiviral therapies combining interferon alfa and ribavirin or a combination of antiprotease and antipolymerase components associated with a genetic prediction of antiviral response and blocking HCV cell entry should improve the long-term prognosis of recurrent hepatitis C in the near future

Efficacité et tolérance de la trithérapie antivirale C (Interféron Pégylé Ribavirine Telaprevir ou Boceprevir) (étude d'une cohorte de 108 patients)

Depuis 2011, le traitement de référence de l'hépatite chronique C de génotype 1 est l'association interféron pégylé, ribavirine et un inhibiteur de protéase (IP) : télaprévir ou bocéprévir. Le but de cette étude était d'évaluer l'efficacité et à la tolérance de ce traitement dans la vraie vie . Patients et méthodes : Etude rétrospective monocentrique de 108 patients consécutifs infectés par le VHC de génotype 1, non sélectionnés, dont le traitement antiviral a commencé entre mars 2011 et mai 2013. Résultats : L'âge moyen était de 53 ans et 73% des patients étaient des hommes : 47% étaient F4 et 14% étaient F3. Le statut vis-à-vis du traitement antérieur était : naïfs 32% des cas, répondeurs-rechuteurs (RR) 28%, répondeurs partiels (RP) 16% et répondeurs nuls (RN) 23%. Après 2, 4, 8 et 12 semaines du traitement avec IP, l'ARN viral était indétectable dans 12%, 50%, 61% et 64% des cas. Parmi les 77 patients suivis 24 semaines après l'arrêt du traitement : le taux global de réponse virologique soutenue (RVS) en intention de traiter était de 55% ; 64% chez les naïfs ; 72% chez les RR ; 38% chez les RP et 31% chez les RN. Pendant les 12 premières semaines de traitement, le taux de survenue d'évènements indésirables graves (EIG) était de 30%. Quatre décès sont survenus. Un taux initial de plaquettes < 100 000/mm3 et un âge ? 53 ans étaient associés à un risque plus élevé de survenue d'EIG. Conclusion : Les taux de RVS dans la vraie vie sont inférieurs d'environ 10% à ceux des études de phase III. La tolérance du traitement est médiocre limitant l'usage des IP. De nouveaux antiviraux sont nécessaires pour traiter les patients notamment les plus graves.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Un modèle d'éducation thérapeutique (l'auto-apprentissage ambulatoire chez le patient diabétique de type 1 à l'Hôtel-Dieu de Paris)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Predictive Factors of Chemotherapy Initiation after Biliary Drainage for Advanced Biliary Tract Cancer: A Retrospective Multicenter Study

International audienceBackground and Aims: In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice. Methods: Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected. Results: Among 82 patients included in this study (median age 68 years, men 61%), 48 (59%) received chemotherapy. Median overall survival was 4.9 months (0.2-38.7) in the group of patients who did not receive chemotherapy and 12.2 months (1.9-61.0) in chemotherapy group (HR=2.93; 95%CI: 1.6-5.3; p&lt;0.0001). In univariate analysis, younger age, male gender, Eastern Cooperative Oncology Group (ECOG) score &lt;= 2, high albumin level, low C-reactive protein level, and endoscopic drainage were significantly associated with introduction of chemotherapy. In multivariate analysis, only ECOG score &lt;2 at diagnosis (HR=70.4; 95%CI: 4.6-1097.6; p=0.002) and male gender (HR=5; 95%CI: 1.5-16.5; p=0.009), were significant independent predictive factors of chemotherapy introduction. Age and bilirubin level at diagnosis were not significant factors in multivariate analysis. Conclusions: ECOG score &lt;= 2 and male gender were the only independent predictive factors of chemotherapy introduction in unresectable biliary tract cancers. Age or initial bilirubin level were not predictors for chemotherapy introduction. These results might help defining the initial therapeutic strategy