bms-790052 and Liver-Failure

Treatment of chronic hepatitis C virus infection has evolved rapidly in recent years due to the invention of interferon-free direct antiviral agents (DAAs). However, evidence and recommendations for acute hepatitis C (AHC) virus infection by DAAs are still limited, especially for those whose disease presents with hepatic decompensation. Here, we report a case with genotype 1b AHC virus infection, complicated by hepatic decompensation and the patient received sofosbuvir and daclatasvir plus low dose ribavirin for 12 weeks. Serum hepatitis C virus RNA significantly declines after therapy and became undetectable at week 8 and it remained undetectable at 12 weeks after finishing therapy; sustained virological response was impressed. Our findings support that combination of sofosbuvir and daclatasvir plus ribavirin can be used for genotype 1b, AHC virus infection patients with overt hepatic decompensation.

Topics: Acute Disease; Aged; Antiviral Agents; Carbamates; Drug Therapy, Combination; Hepatitis C; Humans; Imidazoles; Liver Failure; Male; Pyrrolidines; Ribavirin; RNA, Viral; Sofosbuvir; Sustained Virologic Response; Valine

We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.. Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).. Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child-Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI -2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.. DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.. NCT02097966.

Topics: Adult; Aged; Antiviral Agents; Carbamates; Cohort Studies; Compassionate Use Trials; Drug Monitoring; Drug Therapy, Combination; Europe; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Liver Failure; Male; Middle Aged; Pyrrolidines; Ribavirin; Severity of Illness Index; Sofosbuvir; Treatment Outcome; Valine

Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Isoquinolines; Liver Failure; Liver Transplantation; Middle Aged; Pyrrolidines; Sulfonamides; Treatment Outcome; Valine; Virus Activation

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.

Topics: Alkaline Phosphatase; Antiviral Agents; Bilirubin; Biomarkers; Carbamates; Cholestasis; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C; Humans; Imidazoles; Immunosuppressive Agents; Interferon-alpha; Liver Failure; Liver Transplantation; Middle Aged; Polyethylene Glycols; Pyrrolidines; Recombinant Proteins; Recurrence; Reoperation; Ribavirin; RNA, Viral; Time Factors; Treatment Outcome; Valine; Viral Load