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Background In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. Aim To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). Methods Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. Results A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). Conclusion In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR. [ABSTRACT FROM AUTHOR]

Background Guidelines recommend withholding sofosbuvir ( SOF) in patients with an estimated glomerular filtration rate ( eGFR) of less than 30 mL/min. Aim To assess the risk of acute kidney injury ( AKI) in patients with no renal contraindications for SOF-based treatment. Methods This multicenter retrospective observational study included all consecutive patients that were treated with SOF-based or telaprevir/boceprevir (TVR/BOC)-based regimens at two tertiary university centers in North America. AKI was defined as an increase of ≥0.3 mg/ dL (≥26.5 μmol/L) in serum creatinine level. Multivariable logistic regression analysis was used to identify risk factors for the occurrence of AKI. Results In total, 426 patients were included and treated with a SOF-based regimen (n=233, 54.7%) or TVR/ BOC-based regimen (n=193, 45.3%). Among patients treated with a TVR/ BOC-based regimen 34 (18%) of 193 patients experienced AKI compared to 26 (11%) of 233 patients treated with SOF-based regimens ( P=.056). Multivariable logistic regression analysis showed that the presence of ascites ( OR: 4.44, 95% CI: 1.46-13.54, P=.009) and the use of NSAIDs ( OR: 4.47, 95% CI: 1.32-15.19, P=.016) were associated with a risk of AKI during SOF-based antiviral therapy. Creatinine levels returned to normal at end of follow-up in 23 (88%) of the 26 patients who experienced AKI with a SOF-based regimen and had a creatinine level available during follow-up. Conclusions Although the risk for AKI was lower than for patients treated with TVR/ BOC-based regimens, AKI was seen during 11% of SOF-based regimens and was mostly reversible. Patients with ascites and patients using NSAIDs have an increased risk for AKI during SOF-based antiviral therapy. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Maan et al, and Hussaini and Yoshida papers. To view these articles visit https://doi.org/10.1111/apt.14117 and https://doi.org/10.1111/apt.14161. [ABSTRACT FROM AUTHOR]

Background: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients., Aim: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR)., Methods: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses., Results: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL)., Conclusion: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR., (© 2017 John Wiley & Sons Ltd.)