We thank Drs Benelli and Ventura for their comments on our recent paper.(1) However, we did not conclude that the benefit from UDCA treatment would be too small to recommend it. Rather we stated that the extent of the improvement in pruritus may be too small for most doctors to recommend it or for women to want to take it, and that women and doctors will differ in their view. This conclusion related specifically to pruritus. We also demonstrated a reduction in maternal ALT and AST and in meconium stained-liquor; this latter finding in particular raises the prospect that UDCA confers fetal benefit. An important additional conclusion of the study is that the overall risks and benefits of UDCA to the fetus should be evaluated in a larger trial, which we believe is feasible.

With regard to the biliary transport proteins that are mutated in progressive familial intrahepatic cholestasis, namely ABCB4, ABCB11 and ATP8B1, we agree that genetic variation will be of relevance to disease severity, and likely to treatment response, in some ICP cases. However, we are not aware of any evidence that UDCA is specifically efficacious in pregnancies where the mother carries the above mutations and this was not the focus of the PITCH trial. Previous studies by our group and others have demonstrated that some women with ICP have genetic variation in these transporters.(2) Heterozygous mutations in ABCB4 and ABCB11 occur in approximately 10% of ICP cases and the identification of common variants with a smaller effect upon disease risk is ongoing.(3) We consider it appropriate to perform a more detailed analysis of a large ICP cohort to establish the proportion of cases that have underlying genetic variation (both rare and common variants) in these biliary transport proteins in conjunction with an assessment of the relationship between specific genetic variants, disease severity and treatment response.

(1) Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG; on behalf of the PITCH Study Consortium. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ. 2012 Jun 13;344:e3799. doi: 10.1136/bmj.e3799.

(2) Dixon PH and Williamson C. The molecular genetics of intrahepatic cholestasis of pregnancy. Obstetric Medicine. 2008; 1(2): 65-71

(3) Dixon PH, van Mil SWC, Chambers J, Strautnieks S, Thompson RJ, Lammert F, Kubitz R, Keitel V, Glantz AG, Mattsson LA, Marschall HU, Molokhia M, Moore GE, Linton KJ, Williamson C. Contribution of Variant Alleles of ABCB11 to Susceptibility to Intrahepatic Cholestasis of Pregnancy. Gut. 2009; 58(4): 537-44.

Competing interests: JC is the founder of Obstetric Cholestasis Support UK, a support group for women and families affected by obstetric cholestasis. All other authors declare no competing interests