Ultrasound-guided liver biopsy in children is a procedure with a low rate of major complications and a high rate of minor bleeding not requiring intervention. Treatment with low-dose acetylsalicylic acid did not increase bleeding incidence or total complication rate. Low-molecular-weight heparin and biopsies from focal lesions were risk factors for bleeding complications. Routine ultrasound the day after the procedure did not change handling of the patients.

Aim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004–2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range ¼ 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range ¼ 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range ¼ 1.1-1.9 mM), P < 0.001 for both]. The median pyruvate level was significantly increased only in the rejection group [185 lM (interquartile range ¼ 155-206 lM)] versus the reference group [124 lM (interquartile range ¼ 102-150 lM), P < 0.001], whereas the median lactate/ pyruvate ratio and the median glycerol level were increased only in the ischemia group [66.1 (interquartile range ¼ 23.9-156.7) and 138 lM (interquartile range ¼ 26-260 lM)] versus the reference group [11.8 (interquartile range ¼ 10.6-13.6), P < 0.001, and 9 lM (interquartile range ¼ 9-24 lM), P ¼ 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft-saving treatment. Liver Transpl 18: 839-849, 2012. V C 2012 AASLD. Received December 9, 2011 accepted February 29, 2012.As many as 20% of transplanted liver grafts are lost within the first year despite considerable therapeutic improvements in treatment during the last decades.1 Most grafts are lost within the first week or weeks. As a result, attempts to improve overall graft survival rates should include the early detection and adequate treatment of complications such as acute rejection 2 and vascular occlusion with subsequent ischemia.3 The latter is an especially major contributor to the loss of grafts. Biliary complications and infections are other organ-threatening complications. [4][5][6]

Rejection and ischemia are serious complications after liver transplantation. Early detection is mandatory, but specific markers are largely missing, particularly for rejection. The objective of this study was to explore the ability of microdialysis catheters inserted in liver grafts to detect and discriminate rejection and ischemia through postoperative measurements of inflammatory mediators. Microdialysis catheters with a 100-kDa pore size were inserted into 73 transplants after reperfusion. After the study's completion, complement activation product 5a (C5a), C-X-C motif chemokine 8 (CXCL8), CXCL10, interleukin-1 (IL-1) receptor antagonist, IL-6, IL-10, and macrophage inflammatory protein 1b were analyzed en bloc in all grafts with biopsy-confirmed rejection (n ¼ 12), in grafts with vascular occlusion/ischemia (n ¼ 4), and in reference grafts with a normal postoperative course of circulating transaminase and bilirubin levels (n ¼ 17). The inflammatory mediators were elevated immediately after graft reperfusion and decreased toward low, stable values during the first 24 hours in nonischemic grafts. In grafts suffering from rejection, CXCL10 increased significantly (P ¼ 0.008 versus the reference group and P ¼ 0.002 versus the ischemia group) 2 to 5 days before increases in circulating alanine aminotransferase and bilirubin levels. The area under the receiver operating characteristic curve was 0.81. Grafts with ischemia displayed increased levels of C5a (P ¼ 0.002 versus the reference group and P ¼ 0.008 versus the rejection group). The area under the curve was 0.99. IL-6 and CXCL8 increased with both ischemia and rejection. In conclusion, CXCL10 and C5a were found to be selective markers for rejection and ischemia, respectively. Liver Transpl 18:1421-1429, 2012. V C 2012 AASLD.Received March 30, 2012; accepted June 13, 2012.Most rejections of liver transplants are cellular rather than antibody-mediated, and T lymphocytes are central players.1 Acute cellular rejection (ACR) typically occurs within the first 6 weeks after transplantation and is a relatively frequent complication with an incidence in the range of 30% to 60%.2 The detection and subsequent treatment of ACR are important because the condition may have a negative impact on outcomes, particularly for patients undergoing transplantation for hepatitis C cirrhosis and primary sclerosing cholangitis. [2][3][4][5][6][7] ACR is suspected when the activity of circulating transaminases and/or concentrations of Abbreviations: ACR, acute cellular rejection; ALT, alanine transaminase; AST, aspartate transaminase; AUC, area under the curve; C5a, complement activation product 5a; CI, confidence interval; CXCL, C-X-C motif chemokine; IL, interleukin; IL-1ra, interleukin-1 receptor antagonist; MIP, macrophage inflammatory protein; OLT, orthotopic liver transplantation; s-ALT, serum alanine aminotransferase.

ABSTRACT. Somatomedins are anabolic hormones that may stimulate growth during the perinatal period. To test this hypothesis, neonatal rats were injected with a biosynthetic somatomedin, insulin-like growth factor 1 (IGF-1) twice daily for the first 2 wk of life. Two biosynthetic IGF-1 preparations of different potency were tested as well as a preparation of human growth hormone in five litters of rats. When compared to saline-injected rats, IGF-1 injected rats had increased body weight and tail length as well as specific increases in weights of liver, brain, heart, and testes. In addition, significant increases in bone marrow erythropoietic cell precursors were apparent after IGF-1 injection. IGF-1-treated neonatal rats also exhibited precocious eye opening as a sign of epithelial cell differentiation. Five additional litters of rats received similar injections but were exposed to postnatal nutritional deprivation via artificially increasing litter size. Although IGF-1 caused stimulation of bone marrow erythropoiesis and precocious eye opening, no effects of IGF-1 on somatic or organ growth could be documented. This represents the first demonstration in vivo of the anabolic effects of IGF-1 in rapidly growing neonatal rats but suggests that nutritional sufficiency may also be necessary for the full expression of somatomedin effects. (Pediatr Res 23: 298-305, 1988)

Children with liver transplantation had impaired motor competence compared with healthy children. Ball skills developed adversely several years after liver transplantation, and motor competence did not improve with time after transplantation. Renal function was a significant predictor for motor competence in children with liver transplantation and cholestatic liver disease.

Ischemic vascular complications and rejection occur more frequently with pediatric liver transplants versus adult liver transplants. Using intrahepatic microdialysis catheters, we measured lactate, pyruvate, glucose, and glycerol values at the bedside for a median of 10 days in 20 pediatric liver grafts. Ischemia (n 5 6), which was defined as a lactate level > 3.0 mM and a lactate/pyruvate ratio > 20, was detected without a measurable time delay with 100% sensitivity and 86% specificity. Rejection (n 5 8), which was defined as a lactate level > 2.0 mM and a lactate/pyruvate ratio < 20 lasting for 6 or more hours, was detected with 88% sensitivity and 45% specificity. With additional clinical criteria, the specificity was 83% without a decrease in the sensitivity. Rejection was detected at a median of 4 days (range 5 1-7 days) before alanine aminotransferase increased (n 5 5, P 5 0.11), at a median of 4 days (range 5 2-9 days) before total bilirubin increased 25% or more (n 5 7, P 5 0.04), and at a median of 6 days (range 5 4-11 days) before biopsy was performed (n 5 8, P 5 0.05). In conclusion, microdialysis catheters can be used to detect episodes of ischemia and rejection before current standard methods in pediatric liver transplants with clinically acceptable levels of sensitivity and specificity. The catheters were well tolerated by the children, and no major complications related to the catheters were observed.

Major complications are infrequent after pediatric liver biopsies and no relation between operator experience and major complications was found. We found a significant, but minor, effect of operator procedure frequency on the rate of minor bleeding incidents after ultrasound-guided pediatric liver biopsies.