Biomarkers could be antidote to overdose overtreatment

Researchers have identified several biomarkers that can accurately predict acute liver injury (ALI) after acetaminophen (paracetamol) overdose.

Furthermore, less than 8 hours after drug ingestion, the biomarkers could predict ALI while alanine transaminase (ALT) activity - a standard marker for liver injury - could not.

Authors Kevin Park (University of Liverpool, UK) and team say the findings could help physician decision making and reduce both overtreatment and undertreatment with acetylcysteine antidote, which can cause rare but serious side effects.

The study included 129 patients who had been admitted to hospital with acetaminophen overdose with a median blood acetaminophen concentration of 120 mg/L. All patients required acetylcysteine therapy based on timed blood acetaminophen concentrations.

All of the markers studied - microRNA-122 (miR-122), High Mobility Group Box-1 (HMGB1), full-length and caspase-cleaved Keratin-18 (necrosis and apoptosis K18), and glutamate dehydrogenase - correlated with peak ALT levels during admission.

There were 98 patients who presented with normal ALT (<3 x ULN ALT). Concentrations of each biomarker were significantly higher among the 15 patients in this group who developed ALI than those who did not.

In particular, the authors note that miR-122, HMGB1, and necrosis K18 could predict ALI in these patients at over 90% sensitivity when specificity was 90%, while ALT was a poor predictor for development of ALI with only 9% sensitivity when specificity was 90%.

Furthermore, the biomarkers could also predict ALI among the 63 patients who had their first blood sample taken earlier than the median 8 hours after acetaminophen ingestion. In contrast, there was no significant difference in either serum ALT activity or plasma acetaminophen concentration - which is normally used to determine whether antidote treatment is needed - between patients who did and did not go on to develop ALI.

Writing in Hepatology, the authors say that at present, liver injury can only be excluded after 24-36 hours using liver function tests.

They conclude that, if validated, "the new biomarkers described in this paper may allow earlier exclusion of injury, which would have an impact on hospital bed occupancy and avoid adverse acetylcysteine reactions by reducing unnecessary treatment."

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