From fructose to the future: liver disease biomarkers and their prognostic value in acute liver failure

Acute liver failure (ALF) is an uncommon but severe condition with high morbidity and mortality. Advances in supportive care have improved patient outcomes, but liver transplantation remains the only life-saving intervention in many cases. Unfortunately, healthy donor livers are in short supply. In addition, transplant recipients face several potentially fatal risks including organ rejection, biliary and vascular complications, and infection. It is therefore critical to accurately identify patients who need a new liver while sparing those who do not. This also needs to be done quickly, within the first few days of hospital admission, due to the rapid progression of ALF. Prognostic tools, like the Clichy criteria, the King's College Criteria (KCC), the model for end-stage liver disease (MELD) score, the Acute Liver Failure Study Group Prognostic Index (ALFSGPI), and others have been available for this purpose since at least the 1980s and are commonly used today, but their performance is imperfect, leading to many efforts over the last several decades - and especially in recent years - to identify new noninvasive biomarkers. This review begins with a description of the earliest liver function (e.g. the levulose [fructose] test) and liver injury (e.g. alkaline phosphatase [ALP] and alanine aminotransferase [ALT]) tests and continues through the most recent proposed biomarkers, with critical evaluation of the prognostic utility of each using the KCC and MELD as benchmarks for comparison. Overall, there is as-yet no single biomarker that clearly and consistently performs better than the latter tools, though many may modestly improve the performance of the KCC or MELD when used in combination with them. The search for a better, single biomarker is therefore likely to continue.