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Anti-HCV treatment with ombitasvir/paritaprevir/ritonavir ± dasabuvir is associated with increased bile acid levels and pruritus

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Summary

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.

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Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Rudolf E. Stauber MD, Florian Rainer, Bettina Leber, Andreas Posch, Andrea Streit, Walter Spindelboeck & Vanessa Stadlbauer

  2. Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria

    Günter Fauler & Harald Mangge

  3. Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria

    Harald H. Kessler

  4. Center for Biomarker Research in Medicine (CBmed), Graz, Austria

    Bettina Leber

Authors
  1. Rudolf E. Stauber MD
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  2. Günter Fauler
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  3. Florian Rainer
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  4. Bettina Leber
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  5. Andreas Posch
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  6. Andrea Streit
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  7. Walter Spindelboeck
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  8. Vanessa Stadlbauer
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  9. Harald H. Kessler
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  10. Harald Mangge
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Corresponding author

Correspondence to Rudolf E. Stauber MD.

Ethics declarations

Conflict of interest

R.E. Stauber: Abbvie: research grant, advisory board member, speaker fees, travel grants; BMS: advisory board member, speaker fees; Gilead: advisory board member, speaker fees, travel grants; MSD: advisory board member, travel grants. G. Fauler, F. Rainer, B. Leber, A. Posch, A. Streit, W. Spindelboeck, V. Stadlbauer, H.H. Kessler, and H. Mangge declare that they have no competing interests.

Ethical standards

This study was approved by the Ethics Committee of the Medical University of Graz and informed consent was obtained in accordance with the Declaration of Helsinki

Caption Electronic Supplementary Material

508_2017_1268_MOESM1_ESM.docx

Supplemental Table 1 Serum levels of total bile acids, bilirubin and cholestasis markers before and during OBV/PTV/r ± DSV treatment (n = 20); Supplemental table 2. Serum levels of total bile acids, bilirubin and cholestasis markers before and during OBV/PTV/r ± DSV treatment in patients who reported pruritus (n = 5)

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Stauber, R.E., Fauler, G., Rainer, F. et al. Anti-HCV treatment with ombitasvir/paritaprevir/ritonavir ± dasabuvir is associated with increased bile acid levels and pruritus. Wien Klin Wochenschr 129, 848–851 (2017). https://doi.org/10.1007/s00508-017-1268-x

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  • DOI: https://doi.org/10.1007/s00508-017-1268-x

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