Plasma perfusion combined with plasma exchange in chronic hepatitis B-related acute-on-chronic liver failure patients. BACKGROUND AND AIMS: Artificial liver support systems (ALSS) have been shown to significantly reduce mortality in patients with acute-on-chronic liver failure (ACLF). However, the characteristics of patients who would benefit most from ALSS treatment are poorly understood. This study aimed to delineate the indicators for ALSS and evaluate the effectiveness of plasma perfusion combined with plasma exchange (PP + PE) in patients with hepatitis B virus-related ACLF (HBV-ACLF). METHODS: A total of 898 patients with HBV-ACLF in a single center were enrolled retrospectively. Propensity score matching (PSM) was used in case-paired analysis. Hepatic or extra-hepatic organ failures were defined by Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria. Complications included ascites, infection, hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy and upper gastrointestinal bleeding. Numbers of organ failures or complications were used for risk stratification. RESULTS: Among all patients, 418 patients received standard medical therapy (SMT) and 480 received PP + PE plus SMT. After one-to-one paired PSM within the two groups without risk stratification, 293 pairs were enrolled. The PP + PE group displayed significantly lower mortality risk in both 28- and 90-day observation durations. When stratified, patients with two or more organ failures or complications from the PP + PE group showed greater decrease in mortality risk. Moreover, PP + PE treatment significantly increased the resolution of organ failures and complications and ameliorated the development of new organ failures and complications. CONCLUSIONS: PP + PE treatment significantly reversed organ failures and ameliorated the development of new organ failures and complications, thus reducing mortality risk of patients with HBV-ACLF.