In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium-90 (Y-90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (618) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. Conclusion: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted.

The clinical pictures caused by the arthropod-borne dengue viruses (DEN), which belong to the family of Flaviviridae, vary from a simple febrile fatigue to severe hemorrhagic fever and the often rapidly fatal dengue shock syndrome. 1 Consistent with a worldwide escalation of infection rates during the last decade, the more severe manifestations are occurring in an increasing proportion of cases. 2 Although DEN infections are a particular threat in tropical and subtropical regions, endemic transmission has recently returned to the continental United States. 3 The role of the liver in DEN infection has been generally underestimated, although the infection is regularly associated with elevated liver enzymes. More recent reports suggest the liver to be one of the ultimate target organs and hepatocytes a major site of viral replication in vivo. 4,5 In a frequent number of cases DEN infection causes acute hepatitis with liver failure and hepatic encephalopathy. 6-9 Aside from their own impact on liver cells, DEN provides a potential model for hepatitis C virus (HCV) infection, which at present cannot be grown in cell culture or small animal models.Although the initial steps of infection are a critical determinant of tissue tropism and therefore pathogenesis, little is known about the molecular basis of DEN-or of any other flavivirus-binding to their target cells, and the endocytic itineraries they follow. A growing list of structurally different viruses and certain other microbial agents have been previously shown to utilize sulfated glycosaminoglycans (GAG) such as heparan sulfates (HS) for initial binding to target cells. [10][11][12][13][14][15][16][17] HS is a repeating highly negative-charged linear copolymer of variably sulfated uronic acid and glucosamine carbohydrate residues. 18 Cell surface HS are attached to protein core molecules, some of which are transmembrane proteins with conserved cytoplasmic domains, capable of intracellular signaling. 19 These heparan sulfate proteoglycans (HSPG) provide the main GAG proportion of the cell surface. The presumed physiologic function of these molecules is the promotion of cellular adhesion to the extracellular matrix and the maintenance of boundaries between tissues of different types. 20 They are known to bind a large number of polypeptide growth factors and are involved in intracellular signaling in response to these molecules. 21 HSPG are ubiquitously distributed in the matrix and cell membrane of most tissues, but a distinct cell-and tissue-specific expression pattern 22 may contribute to differential targeting of viruses. They are not believed to be the sole mediator of viral uptake, although endosomal cycling of some HSPG subtypes have been described. 23 This led to the suggestion that infection of different viruses might be a two-or multi-step process, initial contact being with a low-affinity HSPG-receptor followed by transfer to the high-affinity receptor for internalization. 10,24,25 Internalization of flaviviruses is generally believed to be a receptor-med...

Biliary strictures after liver transplantation are a therapeutic challenge for endoscopy. Anastomotic strictures occur in 10% of patients after liver transplantation, leading untreated to mortality and ultimately to graft failure. Despite of successful reports, to date, there is no defined endoscopic therapy regimen for these cases. Therefore the aim of this study was to determine the most suitable concept for endoscopic treatment of post-liver transplant anastomotic strictures (PTAS). A total of 72 patients post-liver transplantation, who received endoscopic retrograde cholangiography (ERC) as a consequence of suspected biliary complications were retrospectively screened for the presence of PTAS. In all patients graft rejection or bile duct ischemia were excluded prior to ERC by liver biopsy or Doppler ultrasound respectively. We compared either balloon dilatation (BD) alone or dilatation plus placement of an increasing number of bile duct endoprostheses (BD ϩ endoprostheses) in a retrospective analysis. A total of 25 of 75 patients showed PTAS. Overall, endoscopic therapy was successful in 22 of 25 patients (88%). BD was initially successful in 89% but showed recurrence in 62%. BD ϩ endoprostheses was initially successful in 87%, and recurrence was observed only in 31%. All recurrences were successfully retreated by BD ϩ endoprostheses. During 22 of 109 (20%) treatment sessions stone extraction was necessary. Complication rate was low with bacterial cholangitis in 8 of 109 (7.3%) sessions, mild pancreatitis in 10 of 109 (9%) sessions and minor bleeding in 2 of 25 (8%) sphincterotomies. Median follow-up after conclusion of endoscopic therapy is 6 months (range 1-43). In conclusion, our data confirm that endoscopic therapy of PTAS is highly effective and safe. As primarily successful BD shows a high rate of recurrence, we recommend a combination of BD followed by an increasing number and diameter of endoprostheses. Therapy sessions are effective at short intervals of every 2-3 months. Liver Transpl 12: 88 -94, 2006.