After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as “bilirubin oxidase.” Functional hepatocytes contain abundant CYP2A6, which is considered a marker for hepatocyte function recovery. The aim of our study was to determine the impact of estradiol/estrogen receptor signaling on bilirubin levels during liver function recovery. We conducted a hospital-based cohort study of bilirubin levels after LDLT surgery in both liver graft donors and recipients, performed a transcriptome comparison of wild-type versus estrogen receptor (ER)α knockout mice and a bioinformatics analysis of transcriptome changes in their regenerating liver after two-third partial hepatectomy (PHx), and assayed in vitro expression of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with 17β-estradiol (E2). The latency of bilirubin level reduction was shorter in women than in men, suggesting that a female factor promotes bilirubin recovery after liver transplantation surgery. In the PHx mouse model, the expression of the cyp2a4 gene was significantly lower in livers from the knockout ERα mice than in livers from their wild-type littermates; but the expression of other bilirubin metabolism–related genes were similar between these groups. Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor) and ESR1 binding to the promoter region of CYP2A6. This is the first report to demonstrate, on a molecular level, that E2/ERα signaling facilitates bilirubin metabolism in regenerating liver. Our findings contribute new knowledge to our understanding of why the latency of improved bilirubin metabolism and thereby liver function recovery is shorter in females than in males.

BACKGROUND:Our recent studies have highlighted the importance and safety of backtable venoplasty for middle hepatic vein (MHV) and inferior right hepatic veins (IRHV) reconstruction using expanded polytetrafluoroethylene (ePTFE) vascular grafts. In t...

Outflow reconstruction in living donor liver transplantation (LDLT) is certainly difficult in limited retrohepatic space with using right liver grafts with venous anomalies. Venoplasty of the inferior right hepatic veins (IRHVs) and middle hepatic vein (MHV) reconstruction using synthetic grafts to form a common outflow channel or a second venocaval anastomosis are available options. We aim to compare outcomes of LDLT recipients who underwent outflow reconstruction with a “V‐Plasty” technique and outcomes of patients who underwent a second venocaval anastomosis. Out of 325 recipients who underwent LDLT from March 2011 to September 2014, 45 received right liver allografts that were devoid of MHV with multiple draining IRHVs (2 or more). Group A (n = 16) comprised the recipients with outflow reconstruction with a V‐Plasty, and group B (n = 29) included the recipients with a second venocaval anastomosis. Group A recipients (male:female, 10:6; median age, 50.5 years) had a mean Model for End‐Stage Liver Disease score of 14.7, whereas for group B recipients (male:female, 20:9; median age, 52.0 years) it was 17.2. The mean IRHV diameter for group A and B grafts was 8.3 mm each. Mean warm ischemia time for group A was significantly lower (25.2 minutes) as compared to group B recipients (34.6 minutes) with P < 0.001. The 2‐month patency rates of vascular grafts were 100% for group A recipients with no evidence of thrombosis. In conclusion, the V‐Plasty technique of MHV and IRHV reconstruction to form a common outflow is a new concept that proves to be a safe and feasible alternative for second venocaval anastomosis. Liver Transpl 22:192‐200, 2016. © 2015 AASLD.