Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25‐50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid‐base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.

Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn’s disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical HLA molecules1. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but lacked the statistical power to define the architecture of association and causal alleles2,3. To address this, we performed high-density SNP typing of the MHC in >32,000 patients with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn’s disease and ulcerative colitis. Significant differences were observed between these diseases, including a predominant role of class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response to the colonic environment in the pathogenesis of IBD.

BackgroundA program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia.MethodsDeclined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate.ResultsTwelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP.ConclusionsNormothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.