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

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.

• Authors: Rudolf E Stauber, Günter Fauler, Florian Rainer, Bettina Leber, Andreas Posch, Andrea Streit, Walter Spindelboeck, Vanessa Stadlbauer, Harald H Kessler, Harald Mangge
• Journal: Wiener klinische Wochenschrift (Wien Klin Wochenschr) Vol. 129 Issue 21-22 Pg. 848-851 (Nov 2017) ISSN: 1613-7671 [Electronic] Austria
• PMID: 28980064 (Publication Type: Journal Article)

Chemical References

• Anilides
• Bile Acids and Salts
• Carbamates
• Cyclopropanes
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Sulfonamides
• ombitasvir
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Adult
• Aged
• Anilides (adverse effects, therapeutic use)
• Bile Acids and Salts (blood)
• Carbamates (adverse effects, therapeutic use)
• Cyclopropanes
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (blood, drug therapy)
• Humans
• Lactams, Macrocyclic
• Macrocyclic Compounds (adverse effects, therapeutic use)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Pruritus (blood, chemically induced)
• Ritonavir (adverse effects, therapeutic use)
• Sulfonamides (adverse effects, therapeutic use)
• Uracil (adverse effects, analogs & derivatives, therapeutic use)
• Valine