Bioartificial liver: present and future

Of course, prevention of liver disease is an important issue; however, as physicians, we have to treat our patients when they come to us, particularly those with life-threatening liver diseases such as acute liver failure. As pointed out in our article (1), liver transplantation remains the treatment of choice for those patients who will not recover with medical treatment. We think that the possibility that bioartificial liver treatment in our patients may have obviated the possibility of liver regeneration and of spontaneous recovery is pure speculation. All our patients included in the trial have the criteria for liver transplantation that we have used since our first experience in liver transplantation for fulminant hepatitis in 1986 (2) and that were confirmed more recently (3). These criteria have not been modified for this bioartificial liver trial, and the decision for liver transplantation for each patient was made before the inclusion in the trial. We agree that the trial was set up to assess safety and tolerability of the system; however, because of the heaviness of the procedure, at the request of health authorities and of our scientific colleagues, we also assessed efficacy. Thus, we monitored the patients closely for clinical and biochemical parameters before and after each course of bioartificial liver treatment and showed a significant neurologic improvement in 6 of 10 patients. As was stated in our article, our patients were not on sedatives, and thus a neurological clinical analysis was possible. It has been suggested in previous trials of artificial or bioartificial liver support that these systems are probably more effective when used at an early stage of liver failure and coma; however; as stated above, all patients fulfilled the criteria for emergency transplantation and were on the waiting list for emergency transplantation. We provided some information on the safety and efficacy of the bioartificial liver in 10 patients. More information on this device will probably come from the multicenter randomized trial currently under way. Our center was one of the first to start a program for emergency liver transplantation for fulminant hepatitis in 1986 (2), and we still believe that liver transplantation was a breakthrough in the treatment of patients with acute liver failure and remains the treatment of choice for most of these patients. However, liver transplantation has its limitations. Some patients died while waiting for a graft, and others died during or after transplantation, either from consequences of brain edema or from sepsis. On an intent-to-treat basis, the survival of those who are candidates for transplantation remains around 50%. One of the main causes of failure is the difficulty to control brain edema (3,4). For all of these reasons, we think there is place for the bioartificial liver system during the waiting time for transplantation to control brain edema. The system we use has its limitations: the use of porcine cells, the low number of these cells, and the short duration of treatment courses. We have described a neurologic improvement in some patients, and we will wait for the results of the multicentric international trial. In the future, we hope to have better, more efficient artificial or bioartificial liver support for our patients. We believe strongly that the development of biological or nonbiological artificial liver support will be a true and necessary challenge in the years to come to aid patients suffering from life-threatening acute and chronic liver diseases.