Rudolf E Stauber1, Günter Fauler2, Florian Rainer3, Bettina Leber3,4, Andreas Posch3, Andrea Streit3, Walter Spindelboeck3, Vanessa Stadlbauer3, Harald H Kessler5, Harald Mangge2. 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. rudolf.stauber@medunigraz.at. 2. Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. 4. Center for Biomarker Research in Medicine (CBmed), Graz, Austria. 5. Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: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.
Entities:
Keywords:
Bile acids; Chronic hepatitis C; Direct acting antivirals; Pruritus
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