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Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30-40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Li, Xu, Zheng, Li, Wang, Huang, Gao, Qian, Liu, Lu, Shang, Li, Wang, Zhang, Meng and Chinese Chronic Liver Failure (CLIF) Consortium.)

Objective: To analyse the difference of genome-wide DNA methylation status of CpG island between the monozygotic twins with disconcordant phenotype of HBV infection and to discover possible differentially methylated genes., Methods: Modified AIMS (amplification of inter-methylated sites) method was adopted. According to the frequent sites of CpG islands (-CGCG- and -CCGG-), three groups of isochizomers with distinct methylation sensitivity (Sma I-Xma I, Hpa II-Msp I and BssH II-Pau I/BseP I) were used to modify the AIMS method. The modified AIMS method combined with Personal Molecular Imager FX system analysis and radioautographic analysis was used to make the global detection of the methylome of CpG islands. Multiple anonymous bands were compared between the twins with the Quantity One bio-soft. The different bands were cloned into T vectors and positive clones were sequenced. BLAST analysis of positive clone sequences was conducted to give the clues for the differential methylated genes between monozygotic twins with discordant phenotype of HBV infection., Results: Nearly the same bands were found between one pair of twins with concordant phenotype of HBV infection. Different methylated bands were found not only between monozygotic twins with concordant phenotype but also between those with disconcordant phenotype. More differential methylated bands were found in the latter groups. By BLAST analysis with sequences of differential methylated bands, four possible genes were got. These genes might relate to the monozygotic twins with disconcordant phenotype of chronic HBV infection., Conclusion: Differential methylation of genes occurs in monozygotic twins with discordant phenotype of HBV infection. Whether these changes are involved in the pathogenesis of different phenotypes needs further elucidation.

Objective: The primary comparative analysis between the host genetic factors and their relationships with clinical phenotype of 20 pairs of HBV infected and high risk twins., Methods: Zygosity of twins was diagnosed by STR microsatellite polymorphism analysis. To identify the serological model and exclude the evidence of coinfection with other virus, we detected HAV, HBV, HCV, HDV, HEV serological markers by electrochemiluminescence method. HBV DNA level was detected by Lightcycler Fluorescent Quantitative system and Liver function (ALT, AST, TBil) was detected by HITACHI7250 Biochemistry Detection System. The data was analysis by Fisher's exact test to comparatively analyze among the monozygotic twins (MZ), dizygotic twins (DZ) and control groups., Results: The significant difference was found in the concordance rate of disease, concordance of clinical phenotype and serological patterns of HBV infection between the MZ and DZ twins (P < 0.05), it was also found between MZ and control groups (P < 0.05), but not between DZ and control groups (P > 0.05). No significant difference in the concordance of other HBV infection markers was observed (P > 0.05). Concordance of clinical phenotype may be related to patients' age and antivirus therapy. Injection with the HBIg and initiative vaccination right after birth can prevent twins with high risk to infection to be victims., Conclusion: The significant difference was found in the concordance rate, concordance of clinical phenotype and serological patterns between MZ and control groups, it was also found between MZ and DZ groups, which is correspond to the opinion of the high concordance of MZ and indicated the host genetic factors may play role in influencing the clinical phenotype, while other factors such as the vaccination may have an effect on the clinical phenotype in some extent.