Efficacy of pegylated interferon α-2b plus entecavir therapy and predictors of treatment success in children with chronic hepatitis B.

Introduction: Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a. Methods: This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting. Results: The study included 76 patients aged 3-18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance. Discussion: These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury.

Background and Aims: The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Methods: Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. Results: MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Conclusion: Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Factors associated with prolonged hospital stay of imported malaria cases in Chengdu, China: a retrospective study.

BACKGROUND: Although China has entered the post-malaria-elimination era, imported cases remain a public health concern in China. METHODS: We retrospectively analyzed data from cases of imported malaria from January 2017 to December 2020 in Chengdu Public Health Clinical Center. We assessed potential clinical, epidemiological, geographical, and seasonal effects on duration of hospital stay. Cox proportional hazards model was used to identify predictive factors for prolonged hospital stay. Multivariate logistic regression was used to assess the potential risk factors associated with severe cases. RESULTS: The highest number of imported cases of malaria were from the Democratic Republic of the Congo (23%, 34/150) and most patients (74%, 26/34) were infected by Plasmodium falciparum. The Edwards test indicated no significant seasonality in imported cases of malaria (χ2 = 2.51, p = 0.28). Bacterial infection (adjusted hazard ratio [aHR] for discharge = 0.58, p = 0.01) and thrombocytopenia (aHR = 0.66, p = 0.02) were risk factors for prolonged hospital stay. The C-reactive protein (OR = 1.02, p = 0.01) and procalcitonin (OR = 1.03, p = 0.01) were risk factors for severe cases. CONCLUSIONS: Bacterial infection and thrombocytopenia are risk factors for prolonged hospital stay among imported malaria cases. The C-reactive protein and procalcitonin level were risk factors for severe cases.

Performance of noninvasive tools for identification of minimal liver fibrosis in patients with hepatitis B virus infection.

BACKGROUND: Various noninvasive liver fibrosis assessment tools are available. Here, we evaluated the performance of the asparagine aminotransferase-to-platelet ratio index (APRI), the fibrosis-4 index (FIB-4), transient elastography (TE), and the globulin-platelet (GP) ratio for identifying liver fibrosis in patients with hepatitis B virus (HBV) infection. METHODS: A total of 146 patients were assessed using TE, FIB-4, APRI, the GP ratio, and liver biopsy. Three patient grouping methods were applied: any fibrosis (AF; F0 vs. F1/2/3/4); moderate fibrosis (MF; F0/1 vs. F2/3/4); and severe fibrosis (SF; F0/1/2 vs. F3/4). Receiver operating characteristic (ROC) curve analysis, univariate analyses, and multivariate logistic regression were conducted. RESULTS: Regardless of patient-grouping method, the area under the curve (AUC) of TE and the GP ratio were similar. Using the AF grouping method, the GP ratio showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.76, 0.75, 0.70, and 0.66, respectively. Using the MF grouping method, the GP ratio also showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.66, 0.68, 0.57, and 0.53, respectively. Using the SF grouping method, the AUCs for the GP ratio, TE, APRI, and FIB-4 were not significantly different. CONCLUSION: Compared with FIB-4 and APRI, the GP ratio had higher accuracy for identifying liver fibrosis, especially early-stage fibrosis, in patients with HBV infection.