This opposite pattern of FGF21 and KLB expression with no consistent change in FGFR4 may indicate a cellular KLB-free state in the early regeneration phase of the damaged liver, and is consistent with our contention that in normal physiology the FGFR4-KLB partnership is a negative regulator of hepatocyte proliferation as well as progression to hepatoma [41,44]. This evidence concerns the gene KLB and hepatocellular carcinoma.