Circulating extracellular vesicles for the diagnosis and dynamic risk profiling of alcoholic hepatitis


Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as novel biomarkers for many diseases and are also implicated in the pathogenesis of AH. Mayo Clinic researchers investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects.

EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) due to cholestatic liver diseases and non-alcoholic steatohepatitis, decompensated alcoholic cirrhosis (AC) and AH. Sphingolipids were quantified by tandem mass spectroscopy. Among AH subjects, EV concentration correlated with MELD score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high EV group and 90.0% in the low EV group (logrank p-value=0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared with healthy controls, heavy drinkers, ESLD and decompensated AC (p=0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH.

Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated alcoholic cirrhosis, and other etiologies of end-stage liver disease and predict 90-day survival permitting dynamic risk profiling.

Sehrawat TS, Arab JP, Liu M, Amrollahi P, Wan M, Fan J, Nakao Y, Pose E, Navarro-Corcuera A, Dasgupta D, Liao CY, He L, Mauer AS, Avitabile E, Ventura-Cots M, Bataller RA, Sanyal AJ, Chalasani NP, Heimbach JK, Watt KD, Gores GJ, Gines P, Kamath PS, Simonetto DA, Hu TY, Shah VH, Malhi H. (2020) Circulating extracellular vesicles carrying sphingolipid cargo for the diagnosis and dynamic risk profiling of alcoholic hepatitis. Hepatology [Epub ahead of print]. [abstract]

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