A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C.

BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. METHODS: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. RESULTS: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). CONCLUSION: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. GOV NUMBER: NCT04695769. IMPACT AND IMPLICATIONS: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.

Impact of pre-transplant infection management on the outcome of living-donor liver transplantation in Egypt.

BACKGROUND AND AIM: Liver transplantation (LT) has emerged as an established therapeutic option for patients with chronic liver disease. Patients with end-stage liver disease are at high risk of infection with multidrug-resistant organisms, which may affect the outcome of LT. The aim of this study was to evaluate the impact of pre-transplant infection on the outcome of living-donor LT. METHODS: Prospective follow-up was done for 50 patients with chronic liver disease who had had LT performed from September 2013 to December 2017. We divided patients into group 1 (patients who had had infection within 3 months before transplantation with adequate treatment [n=20]), and group 2 (patients without infection [n=30]). Both groups were followed for 4 months post-operatively. RESULTS: Patients with high Model for End-Stage Liver Disease scores were more susceptible to infection pre- and post-operatively, and chest infection was the most common infection pre-transplant. There were no significant statistical differences regarding hospital and ICU stay and post-operative course between the groups, but the mortality rate was higher in group 1 (40%) than in group 2 (23.3%), and the causes of mortality in the group 1 were mainly due to medical causes (infections and sepsis, 75%) versus 28.6% in group 2. CONCLUSION: Liver-cell failure and concomitant infection 3 months before LT with adequate treatment had no significant statistical differences regarding hospital, ICU stay, or medical complications, but post-operative infection and mortality rate were more frequent in group 1 and the causes of mortality were mainly medical.