Interpreting liver volume changes after rifampicin in healthy volunteers

Rifampicin-associated liver volume changes in healthy volunteers provide an opportunity to examine the human relevance of xenobiotic-induced liver growth. This Comment considers three aspects of the clinical analysis relevant to interpreting the observed response. Clarification of whether the volumetric outcomes and choice of normalisation were prespecified, alongside paired treatment effects and confidence intervals, would help establish the basis for inference and assess the response's magnitude and precision. For a small volumetric response, blinded repeat segmentation of existing magnetic resonance images and details of scan timing and pre-scan intake would help assess reproducibility under comparable physiological conditions. Associations between 4β-hydroxycholesterol and liver volume could also be examined using within-participant rifampicin-minus-placebo differences, with appropriate attention to the crossover design and an exploratory interpretation. Most of these suggestions could be addressed through protocol information and existing imaging and crossover data, strengthening interpretation of the human findings and guiding further investigation of pregnane X receptor-mediated liver growth.