Therapeutic effect of liver organoids in chronic liver damage from RS/PH. (A) Survival rate of the sham and transplantation group post-transplantation. * p = 0.024332 (log rank test). Sham group n = 22. Transplantation group n = 17. (B) DPPIV/CD26-positive liver organoids repopulated in the RS/PH liver of the DPPIV-negative rats. A total of 3.0 × 103 liver organoids was injected from the portal vein. Images of the quadrate lobe. Thirty, 60, and 120 days post-transplantation are shown. Scale: 1 mm. (C) Repopulation rate of the recipient liver by DPPIV/CD26-positive liver organoids. * p < 0.05, ** p < 0.01 vs. day 30 (one-way ANOVA with Bonferroni correction). (D) CK19 expression of the quadrate lobe. In the sham group, the area of CK19 increased between 30 and 120 days after RS/PH treatment. On the contrary, the CK19-positive area in the transplantation group did not increase. (E) CK19 area in the quadrate lobe. Thirty to 120 days post-transplantation, CK19 areas of the transplantation group were significantly decreased compared with the sham group. Bonferroni correction and Mann–Whitney U test * p < 0.05, ** p < 0.01 vs. sham group (n = 3–4). (F) placental glutathione S-transferase (GST-p) foci of the two groups. Large GST-p-positive foci were observed in the sham group 120 days after RS/PH treatment. (G) Numbers of GST-p-positive foci in the total section of the liver. In the transplantation group, the number of GST-p-positive foci was significantly lower compared with the sham group. * p < 0.05 vs. sham group (Mann–Whitney U test, n = 3–4).