Background. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. Methods. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. Results. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. Conclusion. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality.

The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T‐ and B‐cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver‐derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)‐γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4⁺T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN‐γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN‐γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4⁺T cells to become cytopathic.Conclusions: NK cell‐mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen‐specific T cells, essential for progression of disease. (Hepatology2015;62:1817‐1827)

Aim: The C‐reactive protein (CRP)‐albumin‐lymphocyte (CALLY) index is a novel inflammation‐based biomarker, which has been associated with long‐term outcomes in patients with hepatocellular carcinoma. We aimed to investigate whether the CALLY index can predict the prognosis for distal cholangiocarcinoma after pancreaticoduodenectomy.Methods: The study comprised 143 patients who had undergone primary pancreaticoduodenectomy for distal cholangiocarcinoma between 2002 to 2019. The CALLY index was defined as (albumin × lymphocyte)/ (CRP × 10⁴). We investigated the association of CALLY index with disease‐free survival and overall survival by univariate and multivariate analyses.Results: Eighty‐seven (61%) patients had a preoperative CALLY index <3.5. In multivariate analysis, obstructive jaundice drainage (P < .01), poorly differentiated tumor (P < .01), and CALLY index<3.5 (P = .02) were independent predictors of disease‐free survival, while obstructive jaundice drainage (P < .01), poorly differentiated tumor (P < .01), and CALLY index <3.5 (P = .02) were independent predictors of overall survival.Conclusion: The CALLY index may be an independent and significant indicator of poor long‐term outcomes in patients with distal cholangiocarcinoma after pancreaticoduodenectomy, suggesting the importance of comprehensive assessment for inflammatory status.