I think you have to distinguish between LFT abnormalities as an idiosyncratic reaction to a drug, and those that might relate to the drug's intended activities. We've not seen class effects here, and so my strong belief is that the hep tox in FGEN's earlier trial was specific to that particular compound. The FDA obviously looked at this closely, and with some 1400 patients in Phase 1/2 trials severe idiosyncratic reactions seem unlikely (although obviously still possible with low incidence). The very high potency of the drug (meaning very low absolute dosages) significantly decreases the possibility of idiosyncratic liver tox.
Now ESRD patients do indeed have low LFTs - that seems to be a reflection of their disease. They often have low LFTs even when they should have high LFTs - e.g., when they have HCV or HBV infections. So if we were to magically cure their renal disease, we would actually expect their LFTs (as a population) to increase. Not saying that's what is actually happening here, but it conceivably might be part of the story, namely that the increased LFTs actually reflect improved metabolism.
At the end of the day, for me the MACE endpoints are always going to be more of a concern than these modest increases in LFTs.
Peter
