Background: Although most patients with severe acute hepatitis are conservatively cured, some progress to acute liver failure (ALF) with a high rate of mortality. Based on the evidence that over-activation of macrophages, followed by disturbance of the hepatic microcirculation, plays a key role in ALF, we hypothesized that the production of serum lactate dehydrogenase (LDH) might increase in the liver under hypoxic conditions and could be an indicator to discriminate between conservative survivors and fatal patients at an early stage. Results: To confirm this hypothesis, we developed a new parameter with serum alanine aminotransferase (ALT) and LDH: the ALT-LDH index = serum ALT/(serum LDH - median of normal LDH range). We analyzed retrospectively 33 patients suffering acute liver injury (serum ALT more than 1000 U/L or prothrombin time expressed as international normalized ratio over 1.5 at admission) and evaluated the prognostic value of the ALT-LDH index, comparing data from the first 5 days of hospitalization with the Model for End-Stage Liver Disease (MELD) score. Patients whose symptoms had appeared more than 10 days before admission were excluded from this study. Among those included, 17 were conservative survivors, 9 underwent liver transplantation (LT) and 7 died waiting for LT. We found a rapid increase in the ALT-LDH index in conservative survivors but not in fatal patients. While the prognostic sensitivity and specificity of the ALT-LDH index was low on admission, at day 3 they were superior to the results of MELD. Conclusion: ALT-LDH index was useful to predict the prognosis of the patients with acute liver injury and should be helpful to begin preparation for LT soon after admission. © 2008 Kotoh et al licensee BioMed Central Ltd.