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Mice containing livers repopulated with human hepatocytes would provide excellent in vivo models for studies on human liver diseases and hepatotropic viruses, for which no permissive cell lines exist. Here, we report partial repopulation of the liver of immunodeficient urokinase-type plasminogen activator (uPA)/recombinant activation gene-2 (RAG-2) mice with normal human hepatocytes isolated from the adult liver. In the transplanted mice, the production of human albumin was demonstrated, indicating that human hepatocytes remained functional in the mouse liver for at least 2 months after transplantation. Inoculation of transplanted mice with human hepatitis B virus (HBV) led to the establishment of productive HBV infection. According to human-specific genomic DNA analysis and immunostaining of cryostat liver sections, human hepatocytes were estimated to constitute up to 15% of the uPA/RAG-2 mouse liver. This is proof that normal human hepatocytes can integrate into the mouse hepatic parenchyma, undergo multiple cell divisions, and remain permissive for a human hepatotropic virus in a xenogenic liver. This system will provide new opportunities for studies on etiology and therapy of viral and nonviral human liver diseases, as well as on hepatocyte biology and hepatocellular transplantation. Persistent infection with hepatitis B virus (HBV) is a major worldwide health problem, and chronically infected individuals are at high risk for developing cirrhosis and hepatocellular carcinoma. 1,2 Despite the availability of an HBV vaccine, there are still more than 350 million chronically infected people worldwide, and the few antiviral treatments currently available have a limited rate of efficacy. The narrow host range of HBV and the lack of both in vitro systems and of convenient animal models have greatly hampered our understanding of the complete virus life cycle, as well as the development of more effective antiviral drugs aimed at eradicating the virus from chronic carriers. 3 Chimpanzees are the only animal species infectable with HBV, 4,5 but studies with these animals and evaluation of antiviral therapies are severely restricted because of their limited availability and high costs. Animal models based on HBV-related hepadnaviruses, such as woodchuck and Pekin duck hepatitis B viruses, are often used for assessment of antiviral drugs 6-8 and have provided important information about factors involved in establishment of virus infection, viral persistence, and hepatocarcinogenesis. 9-14 However, woodchucks are relatively large animals of outbred origins that are difficult to handle in many laboratories, and chronic hepadnavirus infection in birds does not lead to cancer. The development of HBV-expressing transgenic mice has also provided important insights regarding viral pathobiology and the role of HBV gene products in hepatocellular injury. 12,[15][16][17][18][19] Although infectious virus can be produced in transgenic mice, their hepatocytes are not permissive for infection. Therefore, the still-unknown early step...

Recently we validated the donor risk index (DRI) as conducted by Feng et al. for the Eurotransplant region. Although this scoring system is a valid tool for scoring donor liver quality, for allocation purposes a scoring system tailored for the Eurotransplant region may be more appropriate. Objective of our study was to investigate various donor and transplant risk factors and design a risk model for the Eurotransplant region. This study is a database analysis of all 5939 liver transplantations from deceased donors into adult recipients from the 1st of January 2003 until the 31st of December 2007 in Eurotransplant. Data were analyzed with Kaplan-Meier and Cox regression models. From 5723 patients follow-up data were available with a mean of 2.5 years. After multivariate analysis the DRI (p < 0.0001), latest lab GGT (p = 0.005) and rescue allocation (p = 0.007) remained significant. These factors were used to create the Eurotransplant Donor Risk Index (ET-DRI). Concordance-index calculation shows this ET-DRI to have high predictive value for outcome after liver transplantation. Therefore, we advise the use of this ET-DRI for risk indication and possibly for allocation purposes within the Eurotransplant region.

The measurement of surgical outcomes, especially in cardiac surgery, has been extensively researched.1 In liver transplantation, several models have been used to identify factors associated with outcomes. [2][3][4][5][6] However, most models are based on data from a single centre; thus their results cannot confidently be extrapolated to other populations of individuals receiving transplants. Furthermore, the models are restricted to an assessment of survival at 12 months after transplantation. Although mortality at 12 months reflects surgical mortality, it also captures mortality associated with recurrent disease, chronic rejection, and retransplantation. Mortality rates at timepoints earlier than 12 months predominantly include surgical mortality, however, and could be associated with different factors to those linked to mortality at 1 year.Data from the European Liver Transplant Registry (ELTR) have been used to establish the intrinsic mortality risk associated with liver transplantation without identified risk factors;8 the results of the study by Adam and colleagues suggest that every centre could assess its own performance by combining this risk with the quoted relative risk ratios of known risk factors. However, the approach used to estimate the risk ratios (proportional hazards regression) does not provide absolute expected mortality rates, thereby limiting the practical application of these results. Furthermore, the results were based on transplants undertaken up to December, 1997. As survival continues to improve after liver transplantation, these models need to be updated. Our aim, therefore, was to assess 3-month and 12-month mortality after first liver transplantation in a cohort of adult recipients from the ELTR who had transplants up to 2003. Methods PopulationThe ELTR database contains information about all liver transplants done in 23 European countries since 1968. 9The methods used to obtain the data and details of the data collected have been described previously, 8 and SummaryBackground Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation.

Living donor and split-liver transplantation techniques require the calculation of a standard liver volume (SLV) as a reference point for the minimal volume necessary for the recipient. We therefore examined whether a widely used formula developed on the basis of a Japanese population sample was also adequate for the Caucasian population. The documentation of volumes of 1332 autopsy livers from a German Forensic Medicine Department was used to create a formula for an SLV for the Caucasian population. The Japanese formula estimated the Caucasian liver volume to be on average 322.6 ؎ 335.8 g (SD) less than they actually were. The following new formula for the calculation of SLV for Caucasians was established by linear regression analysis:Liver volume (mL) ‫؍‬ 1072.8 ‫ء‬ body surface area (m 2 ) ؊ 345.7