Bernard de Hemptinne

Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure

Objective:The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data:In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods:A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results:For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). Conclusions:This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera

A small animal model harboring a functional human liver cell xenograft would be a useful tool to study human liver cell biology, drug metabolism, and infections with hepatotropic viruses. Here we describe the repopulation, organization, and function of human hepatocytes in a mouse recipient and the infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) of the transplanted cells. Homozygous urokinase plasminogen activator (uPA)‐SCID mice underwent transplantation with primary human hepatocytes, and at different times animals were bled and sacrificed to analyze plasma and liver tissue, respectively. The plasma of mice that were successfully transplanted contained albumin and an additional 21 human proteins. Liver histology showed progressive and massive replacement of diseased mouse tissue by human hepatocytes. These cells were accumulating glycogen but appeared otherwise normal and showed no signs of damage or death. They formed functional bile canaliculi that connected to mouse canaliculi. Besides mature hepatocytes, human hepatic progenitor cells that were differentiating into mature hepatocytes could be identified within liver parenchyma. Infection of chimeric mice with HBV or HCV resulted in an active infection that did not alter the liver function and architecture. Electron microscopy showed the presence of viral and subviral structures in HBV infected hepatocytes. In conclusion, human hepatocytes repopulate the uPA+/+‐SCID mouse liver in a very organized fashion with preservation of normal cell function. The presence of human hepatic progenitor cells in these chimeric animals necessitates a critical review of the observations and conclusions made in experiments with isolated “mature” hepatocytes. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270‐9139/suppmat/index.html). (HEPATOLOGY 2005;41:847–856.)

Effectiveness of a new carrier-bound fibrin sealant versus argon beamer as haemostatic agent during liver resection: a randomised prospective trial

Background and aimsA new carrier-bound fibrin sealant, TachoSil, is expected to be efficacious and safe as a haemostatic treatment in hepatic resection.DesignA prospective, randomised, open and controlled multicentre trial with intraoperative as well as postoperative assessment of efficacy and a 1 month follow-up period.SettingTertiary care centres.Patients/methodsOne hundred and twenty-one patients requiring secondary haemostasis during planned liver resection. Patients with coagulation disorders and patients with persistent major bleeding after primary haemostatic measures were excluded.InterventionApplication of either carrier-bound fibrin sealant (n=59) or argon beamer (argon beam coagulator) (n=62) as secondary haemostatic treatment.Main outcome measureTime to intraoperative haemostasis.ResultsThere was a significant superiority of TachoSil over argon beamer with regard to time to haemostasis (3.9xa0min, median 3.0, range 3–20xa0min vs 6.3xa0min, median 4.0, range 3–39xa0min) (P=0.0007). Haemoglobin concentration of drainage fluid was significantly lower on dayxa02 after surgery in TachoSil patients (1.1xa0mmol/l) than in argon beamer patients (2.3xa0mmol/l) (P=0.012). Overall, the frequency and causality of adverse events did not differ between the two treatment groups.ConclusionTachoSil is superior to argon beamer in obtaining effective and fast intraoperative haemostasis. The safety data show TachoSil to be tolerable and safe for haemostatic treatment in liver resection.

Use of topical hemostatic agents during liver resection.

Despite all recent developments in surgical techniques during liver surgery, blood loss is still one of the main causes for postoperative morbidity and mortality. Other complications include bile leakage and fluid accumulation intraperitoneally. Fibrin sealants are able not only to enhance clot formation and wound healing but possibly work as a sealing device for postoperative leakage and fistula formation. In this overview the underlying mechanisms for these agents are discussed and several clinical data concerning liver surgery will be reported.