Epstein‒Barr virus (EBV) is a DNA virus that belongs to the human B lymphotropic herpesvirus family and is highly prevalent in the human population. Once infected, a host can experience latent infection because EBV evades the immune system, leading to hosts harboring the virus for their lifetime. EBV is associated with many diseases and causes significant challenges to human health. This review first offers a description of the natural history of EBV infection, clarifies the interaction between EBV and the immune system, and finally focuses on several major types of diseases caused by EBV infection.

Background: Patients with acute-on-chronic liver failure (ACLF) might be at risk for citrate accumulation during plasma adsorption plus plasma exchange (PE) therapy with regional citrate anticoagulation (RCA). Objectives: To assess the safety and efficacy of RCA during double plasma molecular adsorption system (DPMAS) plus PE therapy for patients with ACLF. Method: A prospective nonrandomized controlled pilot study was conducted at West China Hospital of Sichuan University. Patients with ACLF were enrolled to heparin anticoagulation (HA) group and RCA group. Serial blood samples were taken. Patients were followed up for 3 months. Results: Twenty-four patients with 94 sessions of HA and 28 patients with 106 sessions of RCA were enrolled. RCA method did not affect the therapeutic efficacy, the function of extracorporeal circulation, and the prognosis of these patients. The occurrences of citrate accumulation in RCA group were 0.0, 67.0, 100.0, 34.0, and 0.0% before DPMAS therapy, at the end of DPMAS therapy, immediately after PE therapy, 2 h after PE therapy, and the next morning, while that in HA group were 0.0, 0.0, 100.0, 7.4, and 0.0%, respectively. The occurrences of citrate accumulation at the end of DPMAS therapy and at 2 h after PE therapy in RCA group were much higher than that in HA group (67.0 vs. 0.0%, p = 0.000; 34.0 vs. 7.4%, p = 0.000, respectively). Although the trend of citrate accumulation in RCA group was much more obvious than that in HA group during and after DPMAS plus PE therapy (p = 0.000), the values on the next morning were similar between the 2 groups (p > 0.05). The main alteration of acid–base status was metabolic alkalosis with no difference between the 2 groups. Conclusions: RCA might be safe and effective in patients with ACLF receiving plasma adsorption plus PE therapy. RCA method might offer an alternative anticoagulation method for them.

Background: Hyperbilirubinemia occurs when the liver fails to process bilirubin properly. A disproportionate increase in direct bilirubin indicates a decreased ability of the hepatocytes to uptake and/or convert bilirubin, which may impact the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the association of direct bilirubin to total bilirubin ratio (DB/TB) with outcomes in patients with ACLF remains unclear.Methods: A retrospective study was conducted in West China Hospital of Sichuan University to assess the association between DB/TB and 90-day mortality in patients with ACLF. The diagnosis of ACLF was based on the Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF criteria. Ordinal logistic regression models, linear regression models, and Cox proportional hazards models were applied to evaluate the association between DB/TB and hepatic encephalopathy, disease severity, and outcome, respectively.Results: A total of 258 patients with ACLF were included. The surviving patients were less likely to have liver cirrhosis and comorbidities, and their disease severities were milder than the dead. DB/TB was negatively correlated to cerebral score for hepatic encephalopathy (adjusted odds ratio: 0.01, p = 0.043), and disease severity (adjusted standardized coefficients: −0.42~−0.31, all p < 0.001), respectively. A significant 90-day mortality risk of DB/TB was observed [all adjusted hazard ratio (aHR) < 0.20 and all p ≤ 0.001]. Compared with patients with DB/TB < 0.80, patients with ACLF and DB/TB ≥ 0.80 had much lower 90-day mortality risk (all aHR < 0.75 and all p < 0.01).Conclusion: DB/TB could be an independent risk factor to predict the short-term prognosis in patients with ACLF. More attention should be paid to patients with lower DB/TB due to their poorer prognosis and more urgent need for liver transplantation.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=56960, identifier, ChiCTR2000035013.

Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng’ score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R² = 0.970, p = 0.000). PALS score of 0–2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6–9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3–5 who received 3–5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1–2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6–9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471.