Since insulin resistance (IR) critically exacerbates liver fibrosis in chronic liver diseases, improvement of IR by anti-diabetic agents could serve as a novel therapy to prevent liver fibrosis. In the current study, we elucidated the effect of a sodium-glucose cotransporter-2 inhibitor (SGLT2-I) on liver fibrogenesis in terms of liver fibrosis rat models where porcine serum (PS) was injected intra-peritoneally to congenital diabetic OLETF rat or non-diabetic LETO rat. Different concentrations of ipragliflozin (3 mg/kg and 6 mg/kg) were orally administered during the experimental period. Serological and histological changes were examined at the end of experimental period. Direct effect of ipragliflozin on a human hepatic stellate cell (HSC) line, LX-2, was also evaluated in vitro. OLETF rats developed severe liver fibrosis by PS injection, but not LETO rats. Treatment with ipragliflozin markedly attenuated PS-mediated liver fibrosis and upregulate fibrotic markers along with improvement of IR in a dose-dependent manner in OLETF rats. Intriguingly, in vitro study showed that ipragliflozin affected neither cell proliferation nor fibrogenic activities in HSCs, suggesting that ipragliflozin can attenuate liver fibrogenesis, independent on improving IR. In conclusion, our dataset suggest that SGLT2-I might prevent liver fibrogenesis for NASH, independent of improvement of IR.

Background: End-stage liver disease is often accompanied with portal vein stenosis (PVS) or thrombosis (PVT). The presence of PVS/PVT is sometimes considered as a contraindication to liver transplantation because of difficulty in portal vein reconstruction. In this study, the outcomes of patients with PVS/PVT receiving liver transplantation was evaluated.

Patients and Methods: Clinical features of 151 adult patients receiving liver transplantation in our hospital were retrospectively examined. Among them, 28 patients (18.5%) had PVS/PVT and 12 patients were given modified portal vein reconstruction; cavoportal hemitransposition in 1, jump graft in 2 and renoportal anastomosis in 9.

Results: Postoperative courses were satisfactory in 12 recipients receiving portal vein reconstruction, in whom liver function was maintained. There is no significant difference in rate of change in estimated Glomerular Filtration Rate (eGFR) between the modified portal vein reconstruction group and the control group. The survival rates of patients receiving modified portal vein reconstruction at 1, 5 and 10 years later were 91.7%, 91.7% and 76.4%, respectively; the rates showed no difference comparing to those in control group.

Conclusion: liver transplantation with modified portal vein reconstruction was a life-saving and safe technique for patients with end-stage liver diseases complicating PVS/PVT.