Effectiveness and safety of sofosbuvir‐based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real‐life cohort

Abstract

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Efficacy of generic oral directly acting agents in patients with hepatitis C virus infection

“…A study from Spain reported an overall SVR12 of 93.8% in genotype 3 patients treated with sofosbuvir and daclatasvir combination therapy . Another study in Asian American patients with CHC and advanced liver disease (genotypes 1, 2, 3 and 6), treated with multiple oral DAA combinations, reported a similar overall SVR .…”

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

“…DAA therapy outcomes had variability by genotype, with SVR 92.0% in genotype 1, 89.3% in genotype 2 and 77.1% in genotype 3. Previous studies had reported that HCV genotype 1 and 2 patients achieved higher SVR, with lower response in genotype 3, with our result in line with these findings. The major factor influencing DAA outcomes was unrelated to HCC—the DAA regimen received.…”

Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis

“…We reopened the question of the addition of RBV to the SOF and DCV combination in 2015, when the last patient with liver cirrhosis was referred to antiviral treatment. We decided not to add RBV again, the decision being based on the preliminary data from the two real-life cohorts:32,33 the real-life data demonstrated a higher efficacy of SOF and DCV combination (93.8% SVR rate) also in genotype 3-infected cirrhotic patients in comparison with the ALLY-3 study and the SVR rate in arms with RBV was not significantly better. Nowadays, the EASL 2016 Guidelines2 recommend 12 weeks of SOF and DCV plus RBV or 24 weeks of SOF and DCV as optimal treatment regimen for hemodialyzed patients infected with HCV genotype 3, reflecting the fact that the genotype 3-infected patients with cirrhosis are considered as difficult to treat.…”