Sofosbuvir, velpatasvir, and voxilaprevir for patients with failure of previous direct-acting antiviral therapy for chronic hepatitis C: Results from the German Hepatitis C-Registry (DHC-R)

2020 ◽  
Vol 58 (09) ◽  
pp. 841-846
Author(s):  
Heiner Wedemeyer ◽  
Johannes Vermehren ◽  
Yvonne Serfert ◽  
Markus Cornberg ◽  
Albrecht Stoehr ◽  
...  

AbstractDespite the high effectiveness of direct-acting antivirals for the treatment of hepatitis C, a small proportion of patients do not respond to approved regimens. The combination regimen of SOF/VEL/VOX was recently approved for patients with failure to prior NS5A-based treatment. In this German real-world cohort including patients with cirrhosis (27.3 %) and previous decompensation events, 12 weeks of SOF/VEL/VOX resulted in high virologic response rates irrespective of disease severity and prior DAA regimen. Adverse events were mostly mild or moderate and comparable to those seen in the approval studies.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kao-Chi Chang ◽  
Shui-Yi Tung ◽  
Kuo-Liang Wei ◽  
Chen-Heng Shen ◽  
Yung-Yu Hsieh ◽  
...  

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.


2020 ◽  
Vol 3 (2) ◽  
pp. 01-07
Author(s):  
Dora Lebron

Background: Hepatitis C virus (HCV) is an important cause of chronic hepatitis with necroinflammation and fibrosis resulting in end stage liver disease and hepatocellular carcinoma. Direct acting antivirals (DAAs) are newer agents that directly interfere with the HCV lifecycle and result in high rates of sustained virologic response (SVR). We evaluated if treatment with DAAs in a real-world setting is as successful in HCV/HIV coinfected patients as it is in HCV monoinfected patients, and if some degree of fibrosis regression can be observed after completion of therapy in both groups. Methods: We retrospectively reviewed data from HCV monoinfected and HCV/HIV coinfected patients who received treatment from 2014-2016 at the East Carolina University Infectious Diseases clinic. The primary outcome was to compare completion and sustained virologic response (SVR) rate at either 12 or 24 weeks between HCV monoinfected patients and HCV/HIV coinfected patients. The secondary outcome was to assess regression of fibrosis at either 12 or 24 weeks after completion of therapy, defined as one METAVIR stage improvement in their FibroSure™, a noninvasive biochemical test to estimate the stage of fibrosis. Results: There were 41 patients in each group. Compared to the coinfected group, patient no show rate was higher in the monoinfected group (p=0.0346). In the HCV monoinfected group, 25 (93%) achieved either SVR 12 or 24. Two patients were non-compliant and had detectable viral load on evaluation at week 12. In the HCV/HIV coinfected group, 37 patients achieved SVR (p=0.0039). One patient in the coinfected group did not complete therapy but achieved SVR. In terms of fibrosis, 12/18 (67%) in the monoinfected group demonstrated improvement in at least 1 Metavir stage and 6/18 (33%) had no change. In the coinfected group, 8/16 (50%) patients demonstrated an improvement in FibroSure™ stage, 5/16 (31%) had no change, and 3/16 (19%) had worsening fibrosis according to FibroSure™ stage, (p=0.4867). Conclusions: In this small, real-world cohort, HCV/HIV coinfected patients treated with DAAs had higher completion and SVR rates than HCV monoinfected patients. Treatment failures in the monoinfected group were all linked to non-adherence, whereas, more coinfected patients achieved SVR, likely related to the fact that they were regularly engaged in routine HIV care. Fibrosis regression based on FibroSure™ was observed more in monoinfected patients than those with coinfection. Although not statistically significant, at least 50% of the patients in each group had regression of fibrosis.


2019 ◽  
Vol 221 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Benjamin Emmanuel ◽  
Samer S El-Kamary ◽  
Laurence S Magder ◽  
Kristen A Stafford ◽  
Man E Charurat ◽  
...  

Abstract Background Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. Methods We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. Results The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P &lt; .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P &lt; .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. Conclusions Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.


2019 ◽  
Vol 7 ◽  
pp. 232470961985812
Author(s):  
Clara Y. Tow ◽  
John F. Reinus

In this era of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection, treated patients have extremely high rates of sustained virologic response to short courses of therapy regardless of stage of fibrosis. Treatment failure is uncommon and often attributed to medication noncompliance or viral resistance to drug. This report describes 2 Child-Pugh-A cirrhotic patients who failed to clear HCV in response to therapy with DAAs. Each patient had Roux-en-Y gastric bypass (RYGB) surgery preceding DAA therapy. RYGB may create multiple barriers to adequate DAA absorption as a result of changes in gastrointestinal physiology. Treatment monitoring and duration should be carefully considered in this unique patient population.


Sign in / Sign up

Export Citation Format

Share Document