Liver Failure and Liver Support

It is indeed an honor and privilege to be the Guest Editor of this edition of Seminars in Liver Disease devoted to Liver Failure and Liver Support. The three previous editions devoted to the topic were headed Fulminant Hepatic Failure in 1986, 1996, and 2003, and all profited from the attention of Guest Editor Roger Williams, my mentor and longtime friend. To follow in such large footsteps is daunting! We have broadened the title to include both liver failure and liver support in recognition of the important role we hope liver support will play in the future. While unequivocal success has not been realized, I suspect that great progress will be made before another issue of Seminars unfolds. We have not considered in this issue topics related to chronic liver disease, since this is beyond the scope of a single issue.

The term fulminant hepatic failure is an old one and quite firmly fixed in the clinician's mind, although the term I prefer, acute liver failure, has begun to gain sway. While “fulminant” captures some of the drama of this puzzling condition, it is imprecise and does not indicate much about how the condition evolves. Acute liver failure indicates a short-duration illness and has classically been characterized by coagulopathy with prothrombin time prolongation, more recently characterized by an international normalized ratio (INR) ≥ 1.5, as well as any degree of encephalopathy. Broader definitions include, presumably, milder forms of a similar disease. In children, definitions are based solely on coagulopathy as interpretation of encephalopathy in children can defy the clinician's best effort. Of note, recent workshops have been held in the United States (Bethesda, MD), Europe (Copenhagen), and Japan (Morioka), all in the past year, testifying to the continued importance of this rare syndrome in our thinking.

The present issue begins with a historical perspective, based on more than 40 years of experience with acute liver failure from Professor Williams and Stephen Riordan, then I follow with a review of the etiologies in adults. After all, acute liver failure constitutes a variety of conditions that all carry a common “end game” feature, a multiorgan failure syndrome of devastating consequences. Every organ is truly involved: we know about the brain edema, the renal failure, the increased risk of infection, but are not so aware of the cardiac and pulmonary injury that characterizes the condition. Pediatricians face unique challenges and the pediatric acute liver failure group has played an important role in highlighting these differences. Rob Squires, from the University of Pittsburgh, who has headed this effort, reviews progress in this area. While etiology is important, the role of the innate immune response in reaction to multiple stimuli is an area of increasing new knowledge and no group is better to tackle this than Ray Chung and Anna Rutherford from Harvard Medical School. Drug-induced liver injury (DILI) is covered in detail by Bob Fontana from the University of Michigan, highlighting strides made by another NIH-sponsored network, called DILIN. Julia Wendon, from Kings College Hospital, London, and her coworkers next review current intensive care standards for management; Anne Larson from the University of Texas Southwestern Medical Center in Dallas, and Iris Liou from the University of Washington, Seattle, review the role of transplantation, the single most important advance to date in the management of acute liver failure. As noted earlier, advances in liver support are, we hope, around the corner—this topic is ably covered by Scott Nyberg from Mayo Clinic and his surgical colleagues. Finally, Julie Polson, recently from University of Texas Southwestern Medical Center at Dallas, reviews the current status of outcomes in acute liver failure and the role of prognostic markers in this condition.

Several significant advances have been made over the more than two decades since Seminars first covered fulminant hepatic failure. Liver transplantation is first and foremost. Others include the more careful delineation of etiologies as prognosis (as well the use of antidotes) is largely dependent on this; the recognition of the huge part acetaminophen plays in present-day acute liver failure; and the collaborative study of larger groups of patients through the use of established clinical networks. The use of N-acetylcysteine (NAC) for non-acetaminophen liver failure and of hypothermia for management of cerebral edema, while not fully realized, both represent new hope since either can be applied without the need for highly technological equipment.

The future for the field is bright as new developments increase with warp speed. I am delighted to present the current edition of Seminars in Liver Disease and hope you enjoy this thorough update of current knowledge in the field.