Search

Background: The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood., Methods: We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT., Results: In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently ( P = 0.027)., Conclusions: At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI)., Methods: In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cutoff values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n = 6) to identify transplantable liver grafts with low BDI., Results: Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared with high BDI. The following cutoff values were associated with low BDI: biliary bicarbonate greater than 18 mmol/L (P = 0.002), biliary pH greater than 7.48 (P = 0.019), biliary glucose less than 16 mmol/L (P = 0.013), and bile/perfusate glucose ratio less than 0.67 (P = 0.013). In the clinical trial, 4 of 6 livers met these criteria and were transplanted, and none developed clinical evidence of posttransplant cholangiopathy., Conclusions: Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point of care, making them suitable for the pretransplant assessment of bile duct viability. This may improve graft selection and decrease the risk of posttransplant cholangiopathy.