Efficacy and predictive factors of glucocorticoid therapy for patients with hepatitis B virus-related acute-on-chronic liver failure.

Background and study aims: Glucocorticoid (GC) treatment for liver failure is controversial. This study sought to evaluate the efficacy and predictive factors of glucocorticoid therapy for hepatitis B virus-related acute-on-chronic liver failure (HBV- ACLF). Patients and methods: A total of 302 patients with HBV- ACLF were enrolled and categorized by treatment modality (GC vs. Control). Baseline characteristics, liver function, disease complications, and mortality were recorded. Univariate and multivariate analysis were used to identify predictive factors for HBV-ACLF-related mortality. Results: GC therapy significantly improved the 30- and 60-day mortality of HBV-ACLF patients (4.64% vs. 11.92%, P=0.022 and 16.56% vs. 25.83%, P=0.049 for the Control and GC groups, respectively) and GC was an independent prognostic factor for 30-day mortality (OR = 0.177, 95% CI 0.051-0.616, P = 0.007). However, enhanced survival was not associated with improved liver function. There were no significant differences in the incidence of complications (i.e., ascites, bacterial infection, encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding) between the GC and Control groups (P >0.05), except that fungal infection occurred with higher frequency in the GC group (P = 0.037). A significant improvement in the 30-day survival associated with GC therapy was observed among patients <40 years of age, a Model for End-stage Liver Disease (MELD) score of 25-35 or a CLIF- Consortium ACLF (CLIF-C ACLF) grade 0-1 (all P <0.05). Conclusions: GC therapy improved the short-term (30- and 60- day) mortality of patients with HBV-ACLF. This treatment may be of particular benefit to patients who are <40 years of age, have a MELD score of 25-35, or have a CLIF-C ACLF grade of 0-1. (Acta gastroenterol. belg., 2022, 85, 593-600).

[Clinical and prognostic significance of ABO promotor methylation level in adult leukemia and myelodydysplastic syndrome].

Objective: To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods: ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR.Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results: The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, P<0.05). The methylation rates in remission AML and ALL were 1.58% and 2.30% respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50% respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months)(P<0.05).The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M(3)) patients. Conclusion: ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.

[Effects of DNA methylation on ABO gene expression in leukemia].

Objective: To investigate the impact of promoter CpG island methylation on ABO mRNA expression in leukemia. Methods: 25 cases of leukemia and 20 cases of normal control were studied, and the leukemia cell lines K562、HL-60 and Jurkat were treated with different concentrations of decitabine. PCR-SSP was used to identify ABO genotype, RQ-PCR for ABO mRNA expression and bisulfite sequencing PCR for DNA methylation status. Results: ① The methylation of ABO promoter in acute myeloid leukemia patients (10 cases) and acute lymphoblastic leukemia patients (10 cases) were 53.85% and 18.22% respectively, which were obviously higher than those in control (20 cases, 2.33%) and chronic myeloid leukemia patients (5 cases, 2.12% ). ② ABO genotype of K562 was O1O1, which has changed little before and after decitabine treatment. ABO genotype of HL-60 and Jurkat could not been identify before treatment, but showed as O1A1 and A1O2 after treatment. ③ABO mRNA expression of K562 was 1 275.67 ± 35.86, which was obviously higher than that in HL-60 (0.54 ± 0.07, P<0.05) and Jurkat (0.82±0.16, P<0.05). ④The methylation of ABO promoter in K562, HL-60 and Jurkat were 0, 58.14%, and 96.74%. As concentration of decitabine increased, the methylation of ABO promoter were decreased and the expressions of ABO mRNA were increased in HL-60 and Jurkat, which had significant differences compared with that before treatment (P<0.05). Conclusion: The methylation of ABO promoter shows a negative correlation with ABO mRNA expression. DNA methylation was an important aspect of ABO antigens decrease in acute leukemia.