Transplantation for Fulminant Hepatic Failure

Data from the Scientific Registry of Transplant Recipients (SRTR) and the European Liver Transplant Registry (ELTR) indicate comparable levels of liver transplantation for fulminant hepatic failure (FHF), representing around 8% of overall organ utilization. A single-center (King’s College Hospital) experience of 2095 patients with FHF and at least grade 2 encephalopathy had a 19% transplantation rate, but this increased to 53% of nonacetaminophen cases and 35% of acetaminophen cases by the end of the study period in 2004-2008 ( Table 12-1 ). The application of liver transplantation also varied with cause and in the United States was notably lower at only 8% in patients with acetaminophen-related FHF as compared with about 40% of cases with other causes.

It is frequently stated that liver transplantation is the only effective treatment for FHF. This statement has some credibility in that liver transplantation is the intervention that has made the single most visible contribution to the improvement in survival in patients with FHF, particularly in those with clear-cut evidence of an inherent poor prognosis. The concept of replacing a failing liver in a young patient with only a few days to live is a graphic illustration of the power of liver transplantation, especially because the outcomes proved to be very acceptable with respect to survival and long-term rehabilitation. The concept was initially applied in the early 1980s, and by 1995 the feasibility of liver transplantation had been established in a series of patient with survival rates peaking at over 90% at 1 year.

Although liver transplantation was a revolution, a parallel evolution of advances in critical care, by means of small steps rather than quantum leaps, also contributed to improved survival rates without transplantation. In the King’s College Hospital series, nontransplant survival increased from 16.7% at baseline to 48% ( Fig. 12-1 ). The improved survival was seen in acetaminophen patients and in patients with drug-induced liver injury and hepatitis A or B. However, the improved survival was not seen in patients with seronegative hepatitis or FHF of indeterminate cause.

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Improvement in survival from baseline (1984-1993) to end of study (2004-2008) in over 3300 patients treated at King’s College Hospital.

The efficacy of liver transplantation was never established in a randomized controlled trial or even a carefully constructed case comparison study. In 1990 an argument was made for a “controlled trial between specialist units…to establish the role of emergency hepatic transplantation in patients with fulminant hepatic failure,” but this fell on deaf ears then and is unlikely to be received with any great enthusiasm over 20 years later. The arguments in support of such a trial were scientifically sound but were silenced by counterarguments that careful selection of patients with the worst prognosis would deliver survival benefit well beyond that which need to be demonstrated in a randomized controlled trial. This view continues to dominate the evaluation of the role of liver transplantation in the management of FHF.

Listing for Liver Transplantation

The principles driving selection processes are the accurate identification of those in need of and those who will benefit from liver transplantation. Broadly, there are two approaches to listing patients with FHF for liver transplantation. The first is to use some set of indicators of a poor prognosis to discriminate for the purposes of wait-listing; the second is to list all eligible patients and defer the decision until a donor organ becomes available. The first approach requires the selection process to have a high level of confidence that each individual patient would benefit from a liver transplant. In this context, failure to list a patient for liver transplantation who subsequently dies is a visible and regrettable event. The potential for “unnecessary transplantation” is greatest for acetaminophen-related FHF. In one series from the United States 59% of patients wait-listed for transplantation but not transplanted survived ( Fig. 12-2 ), whereas the survival rate in those receiving transplants was 78%. The second approach favors the individual patient but risks unnecessary transplantation, which is a less visible but also regrettable outcome given that a scarce organ could have been better used. These clinical tensions are reflected in how prognostic models are used and evaluated with respect to sensitivity and specificity.