Predicting outcome in acute liver failure: Are we there yet?

The simple answer to the question in the title is “no”. The complex answer involves looking into the “crystal ball” of prognostic markers yet again. “Fulminant hepatic failure” or acute liver failure (ALF) is a rare disorder which has devastating consequences. Predicting which patients require liver transplantation can be difficult at times. Early transplantation of a patient with hyper-acute liver failure secondary to paracetamol (acetaminophen) may be unnecessary. Late transplantation can reduce the chance of a successful outcome. The ideal prognostic marker should have high sensitivity and specificity allowing for prognostic information to be of clinical use early in the disease course. All prognostic models have their limitations. The most widely used are the King’s College Hospital (KCH) criteria. These were derived from a cohort of 588 patients presenting with acute liver failure during 19731985. They have clearly demonstrated the importance of underlying etiology in determining prognosis of ALF. They have been evaluated by other groups and are now benchmarked against all new prognostic markers of ALF. A review of the practical use of the KCH criteria is found elsewhere. The KCH criteria for paracetamol (POD)-induced ALF have been subject to a meta-analysis which revealed that although the criteria were specific, the sensitivity was low, suggesting that a number of patients who don’t fulfill criteria will die without transplantation. More recently, a prospective study demonstrated that the addition of arterial blood lactate levels to the KCH POD criteria increased their sensitivity. However, the full impact of arterial blood lactate measurements as a prognostic marker in POD-induced ALF remains to be determined. There is no doubt that modern intensive care has improved outcomes in POD-induced ALF. This is reflected in increasing spontaneous survivor rates in this group of patients relative to patients with non–PODinduced ALF whose prognosis remains poor without transplantation. Even when patients fulfill KCH POD criteria or are listed for liver transplantation, it appears that an increasing percentage of them survive without grafting. Other prognostic markers of ALF include the Clichy criteria, which was developed from a cohort of 115 patients with ALF secondary to HBV infection. They define a poor prognosis by the grade of hepatic encephalopathy and factor V levels. The KCH and Clichy criteria have been compared as prognostic markers in ALF, and the KCH criteria have gained more widespread use due in part to the lack of readily available factor V level measurements. Further prognostic markers for POD-induced ALF have been developed and include serum phosphate levels, the MELD (Model for End-Stage Liver Disease) score, and APACHE II measurements. None have gained widespread use. It is possible that APACHE III measurements may supplement the KCH criteria by identifying nonsurvivors among patients who do not fulfill the KCH POD criteria. Newer prognostic markers undergoing evaluation for non–POD-induced ALF include the MELD score and arterial blood lactate levels. In this issue, Schiødt et al. test the predictive value of actin-free Gc-globulin in ALF. The plasma protein Gc-globulin (also known as vitamin D–binding protein) is a multifunctional protein whose properties include transporting vitamin D metabolites and actin scavenging. The authors previously showed that serum concentrations of Gc-globulin have prognostic value in