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Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA-mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis. In patients with HBV-ACLF meeting COSSH-ACLF criteria, age, liver cirrhosis and INR were independent risk factors for 28-day and 90-day poor prognosis. COSSH-ACLF