Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Wien Klin Wochenschr. 2017 Nov;129(21-22):848-851. doi: 10.1007/s00508-017-1268-x. Epub 2017 Oct 4.
Direct acting antiviral (DAA)-based treatment with ombitasvir/paritaprevir/ritonavir ± dasabuvir (OBV/PTV/r ± DSV) is highly effective in HCV genotype 1 or 4 infection and well-tolerated with only few side effects. However, pruritus has been observed in several trials in up to 20% of patients and seems to be unique for this DAA combination.
The aim of this preliminary study was to investigate the effect of OBV/PTV/r ± DSV on bile acid levels and to correlate them to the emergence of pruritus during treatment.
Twenty patients with chronic hepatitis C genotype 1 or 4 were treated for 12 or 24 weeks with OBV/PTV/r ± DSV with or without ribavirin. Side effects including pruritus were assessed every 4 weeks during treatment or on demand. Blood was collected in fasting state at baseline and at treatment week 4 for determination of bile acid concentrations by high-resolution mass spectrometry.
Pruritus developed in 5 out of 20 patients during the first 4 weeks of DAA treatment. Pruritus was self-limiting during DAA treatment in 4 patients while one patient required cholestyramine treatment and responded well. Total bile acid levels increased approximately 4‑fold by treatment week 4.
Pruritus observed during OBV/PTV/r ± DSV treatment of chronic hepatitis C is associated with increased on-treatment serum bile acid levels, possibly due to ritonavir-induced alterations of bile acid transport.
基于直接作用抗病毒药物（DAA）的 ombitasvir/paritaprevir/ritonavir±dasabuvir（OBV/PTV/r±DSV）治疗方案对 HCV 基因 1 或 4 型感染具有高度疗效，且耐受性良好，仅有少数副作用。然而，在几项试验中，多达 20%的患者观察到瘙痒，并且似乎是这种 DAA 联合方案所特有的。
本初步研究旨在探讨 OBV/PTV/r±DSV 对胆汁酸水平的影响，并将其与治疗期间瘙痒的发生相关联。
20 例慢性丙型肝炎基因 1 或 4 型患者接受 OBV/PTV/r±DSV 联合或不联合利巴韦林治疗 12 或 24 周。在治疗期间或按需每 4 周评估副作用，包括瘙痒。在基线和治疗第 4 周空腹时采集血液，通过高分辨率质谱法测定胆汁酸浓度。
在 DAA 治疗的前 4 周，有 5 例患者出现瘙痒。在 4 例患者中，瘙痒在 DAA 治疗期间自行缓解，而 1 例患者需要接受考来烯胺治疗并反应良好。治疗第 4 周时，总胆汁酸水平增加了约 4 倍。
在慢性丙型肝炎患者接受 OBV/PTV/r±DSV 治疗期间观察到的瘙痒与治疗期间血清胆汁酸水平升高有关，这可能是由于利托那韦诱导的胆汁酸转运改变所致。
