Drug- and alcohol-induced liver injury makes up the majority of the cases of liver failure and transplantation. Extracellular vesicles (EVs) have been proposed as the source of biomarkers by the virtue of comprising unique proteins reflecting the identity and tissue-specific origin of the EV proteins. 

A study determined if potentially hepatotoxic agents like acetaminophen (APAP) and binge alcohol, could increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. 

APAP-exposed, ethanol-fed mice or alcoholic hepatitis patients and normal control counterparts were utilized to isolate the circulating EVs in plasma which was then subjected to further analysis.

The following observations were made-

• Circulating EVs from APAP-treated mice showed a marked elevation in the amounts of total and liver-specific proteins in a dose- and time-dependent manner. 
• EVs from APAP-exposed mice showed increased amounts of liver-specific and/or hepatotoxic proteins than the controls, in Proteomic analysis.
• The increased protein amounts in EVs after APAP exposure returned to basal levels after treating mice with N-acetylcysteine or glutathione. 
• Identical observations of increased amounts and liver-specific proteins in circulating EVs was also seen in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. 
• A marked increase in the liver-specific proteins in circulating EVs was observed after binge ethanol exposure in mice and alcoholics with alcoholic hepatitis, then the control counterparts. 

Thus this study proves that the circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins which could serve as specific biomarkers for hepatotoxicity.

Source- Cho YE, Im EJ, Moon PG, Mezey E, Song BJ, Baek MC. Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury. PLoS ONE 2017;12(2): e0172463. https://doi.org/10.1371/journal.pone.0172463