Background We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. Methods Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. Results During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Se...

https://www.nejm.org/doi/pdf/10.1056/NEJM199510263331702

Hepatic failure and lactic acidosis due to fialuridine (fiau), an investigational nucleoside analogue for chronic hepatitis b

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840210137

Fulminant Hepatic Failure: Summary of a Workshop

Long-term storage of tissues by cryopreservation: critical issues

Pilot‐controlled trial of the extracorporeal liver assist device in acute liver failure

Objective The purpose of this study was to develop a bioartificial liver (BAL) to treat patients with severe liver failure until they can be either transplanted or recover spontaneously. Background Data Severe acute liver failure is associated with high mortality. Liver transplantation has emerged as an effective therapy for patients who did not respond to standard management. However, because of the donor organ shortage and urgent need for transplantation, many patients die before they can be transplanted and others do not survive after transplantation, primarily because of intracranial hypertension. Methods ' Three groups of patients with severe acute liver failure were treated with the BAL. In group 1 (n = 18) were patients with fulminant hepatic failure (FHF), in group 2 (n = 3) were patients with primary nonfunction (PNF) of a transplanted liver, and in group 3 (n = 10) were patients with acute exacerbation of chronic liver disease. Patients in groups 1 and 2 were candidates for transplantation at the time they entered the study, whereas patients in group 3 were not. Results In group 1, 16 patients were bridged successfully to transplantation, 1 patient was bridged to recovery without a transplant, and 1 patient died because of concomitant severe pancreatitis. In group 2, all patients were bridged successfully to retransplantation. In group 3, two patients were supported to recovery and successful transplants at later dates; the other eight patients, although supported temporarily with the BAL, later died because they were not candidates for transplantation. Conclusions The authors' clinical experience with the BAL has yielded encouraging results. A randomized, controlled, prospective trial (phase II-III) is being initiated to determine the efficacy of the system.

Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840160112

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840150225

An improved model of acetaminophen-induced fulminant hepatic failure in dogs.

We have used an anhepatic dog model to demonstrate the efficacy of a bioartificial liver assist device. Six dogs underwent total hepatectomy. Three received only medical care (controls) while the remainder were connected to an extracorporeal liver assist device (ELAD). The control dogs failed to regain consciousness after anesthesia although all lived 4-5 h postoperatively. Plasma ammonia concentration increased by an average of 250 mumol/L between the end of surgery and the demise of the animals. The treated dogs lived 3-12.5 h, and 2 of them required repeated doses of thiamylal sodium to maintain sedation. Plasma ammonia concentration was unchanged after connection to the ELAD except in the longest survivor, whose ammonia began to rise after 8 h on the ELAD. The short survival in the other 2 treated dogs was the result of uncontrolled intraabdominal bleeding. This device is capable of replacing the metabolic function of the liver, and might provide hepatic support in patients awaiting transplantation or in fulminant hepatic failure.

Maria G. Chong

Papers

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

An improved model of acetaminophen-induced fulminant hepatic failure in dogs.

Assessment of an Extracorporeal Liver Assist Device in Anhepatic Dogs