Figure S1 Hepatocytes persistently affected by transforming growth factor (TGF)-β together with pro-inflammatory cytokines come to exhibit carcinogenic pSmad3L (Ser 208/213) and fibrogenic pSmad2L (Thr 220)/C signaling.

Figure S2 Phospho-Smad3 signaling after hepatitis C virus (HCV) clearance. (a) Chronic hepatitis C can be cured if patients are treated with interferon (IFN) therapy that terminates chronic inflammation by eradicating HCV populations. In chronic hepatitis C, pSmad3L signaling initially depends on presence of chronic inflammation: cessation of chronic inflammation restores hepatocytic tumor-suppressive pSmad3C signaling, as occurring in normal hepatocytes, from carcinogenic pSmad3L signaling. (b) Other patients with advanced fibrosis have evolved beyond dependence on inflammation. Their preneoplastic hepatocytes constitutively carry out carcinogenic pSmad3L signaling, possibly caused by genetic and epigenetic carcinogenic factors, despite a blunted inflammation.

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