Background Re-treatment in patients with a chronic hepatitis C virus (HCV) infection and a previous failure to direct-acting antiviral (DAA) treatment remains a challenge. Therefore, we investigated the success rate of treatment and re-treatment regimens used at our center from October 2011 to March 2018. Methods A retrospective analysis of DAA-based HCV therapies of 1096 patients was conducted. Factors associated with a virological relapse were identified by univariable and multivariable logistic regression, treatment success of the re-treatment regimens was evaluated by an analysis of sustained virological response (SVR) rates in patients with a documented followup 12 weeks after the end of treatment. Results Of 1096 patients treated with DAA-based regimens, 91 patients (8%) were lost to follow-up, 892 of the remaining 1005 patients (89%) achieved an SVR12. Most patients (65/113, 58%) who experienced a virological relapse received an interferon-based DAA regimen. SVR rates were comparable in special cohorts like liver transplant recipients (53/61, 87%) and people with a human immunodeficiency virus (HIV) coinfection (41/45, 91%). On multivariable analysis, interferon-based DAA therapy was associated with treatment failure (odds ratio 0.111, 95%-confidence interval 0.054-0.218) among others. One hundred seventeen patients with multiple DAA treatment courses were identified, of which 97 patients (83%) experienced a single relapse, but further relapses after two (18/117, 15%) or even three (2/ 117, 2%) treatment courses were also observed. Eighty-two of 96 (85%) re-treatment attempts with all-oral DAA regimens were successful after an initial treatment failure.

Direct‐acting antiviral (DAA) therapies have revolutionized the treatment of chronic hepatitis C virus infection, achieving sustained virological response (SVR) rates of >90% even in patients with advanced liver cirrhosis. Having observed an unusual case of repeated DAA therapy failures in a patient with a transjugular intrahepatic portosystemic shunt (TIPS), we assessed a possible association between prior TIPS placement and DAA failure. A structured search of our clinical database revealed 10 patients who had received DAA therapy after TIPS placement. At the time of therapy, most patients (8; 80%) presented with a Child‐Pugh score B, and the following DAA regimens were used: sofosbuvir/ledipasvir ± ribavirin (5 patients), sofosbuvir/daclatasvir ± ribavirin (3), sofosbuvir/velpatasvir (2), and sofosbuvir/velpatasvir/voxilaprevir (1). In total, 5 patients (50%) achieved an SVR, whereas a virological relapse occurred in the other half of the cases, including 2 patients with multiple relapses. In this patient cohort, SVR rates were unusually low for all regimens: sofosbuvir/ledipasvir ± ribavirin, 3/5 (60%); sofosbuvir/daclatasvir ± ribavirin, 2/3 (66%); sofosbuvir/velpatasvir, 0/2 (0%); and sofosbuvir/velpatasvir/voxilaprevir, 0/1 (0%), and patients with a TIPS made up a relevant proportion of DAA failures in patients with cirrhosis at our center: sofosbuvir/ledipasvir, 2/18 (11%); sofosbuvir/daclatasvir, 1/4 (25%); sofosbuvir/velpatasvir, 2/3 (66%); and sofosbuvir/velpatasvir/voxilaprevir, 1/1 (100%). Conclusion: We observed a high rate of virological relapse in patients with a TIPS who received DAA treatment and therefore postulate that TIPS placement may be a possible risk factor for DAA failure due to the profound hemodynamic changes evoked by the intervention. Longer treatment duration or addition of ribavirin might be warranted in these patients.

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