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The hypothesized model of circulating histones in mediating systemic inflammation and liver injury. It is proposed that circulating histones may originate from cell damage or death caused by virus, bacteria, hepatotoxins, or trauma, then inducing direct cytotoxicity and activation of innate immunity and systemic inflammation, which in turn attracts more inflammatory cells and amplify inflammation by promoting cytokine production that eventually contribute to the pathogenesis of ALF
