High normal alanine aminotransferase is an indicator for better response to antiviral therapy in chronic hepatitis B.

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.

Trichinella-derived protein ameliorates colitis by altering the gut microbiome and improving intestinal barrier function.

BACKGROUND: Inflammatory bowel disease (IBD) encompasses Crohn's Disease and Ulcerative Colitis. Reports have highlighted the potential use of helminths or their byproducts as a possible treatment for IBD; however, the mechanisms underlying their ability to modulate inflammation remain incompletely understood. In the present study, we analyze the possible mechanism of a serine protease inhibitor from adult T. spiralis excretion-secretion products (rTsSPI) on the improvement of colitis. METHODS: The immune protective effect of rTsSPI was studied by using DSS or Salmonella-induced colitis in female C56BL/6 mice. The effect of rTsSPI on the immune and inflammatory responses, gut microbiota, permeability of colon epithelium and junction proteins was analyzed. RESULTS: Treating mice with rTsSPI induced type 2 immunity and significantly attenuated clinical symptoms, macroscopical and histological features of DSS or bacteria-induced colonic inflammation. This was accompanied by decreasing neutrophil recruitment in the colonic lamina propria, and reducing TNF-α mRNA levels in the colon; in contrast, the recruitment of M2 macrophages, the expression level of IL-10 and adhesion molecules increased in the colon tissue. Moreover, treatment with rTsSPI led to an improvement in gut microbiota diversity, as well as an increase in the abundance of the bacterial genera Bifidobacterium and Ruminclostridium 5. CONCLUSIONS: Collective findings suggest that pretreatment with rTsSPI can ameliorate colitis in mice by inducing a Th2-type response with M2 macrophages. Data also indicate that immunotherapy with rTsSPI represents an additional strategy to ameliorate inflammatory processes in IBD by enhancing probiotic colonization and maintaining intestinal epithelial barrier function.

Preexisting Trichinella spiralis infection attenuates the severity of Pseudomonas aeruginosa-induced pneumonia.

BACKGROUND: A range of helminth species involve the migration of developing larvae through the lung and establish chronic infections in the host that include potent immune regulatory effects. Trichinella spiralis is one of the most successful parasitic symbiotes. After released by intestinal female adult worms, newborn larvae of T. spiralis travel through the circulatory system to the lung and finally reach skeletal muscle cells. As unique inflammation modulator of intracellular parasitism, T. spiralis shows improved responses to autoimmune disease and viral pulmonary inflammation by exerting immunomodulatory effects on innate and adaptive immune cells. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice were divided into four groups: uninfected; helminth- T. spiralis infected; P. aeruginosa infected; and co-infected. Mice infected with T. spiralis were incubated for 6 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage fluid, blood and lung samples were analyzed. We found that T. spiralis induced Th2 response in the mouse lung tissue, increased lung CD4+ T cells, GATA3, IL-4, IL-5 and IL-13 expression. Pre-existing T. spiralis infection decreased lung neutrophil recruitment, inflammatory mediator IL-1ß and IL-6 expression and chemokine CXCL1 and CXCL2 release during P. aeruginosa- pneumonia. Furthermore, T. spiralis co-infected mice exhibited significantly more eosinophils at 6 hours following P. aeruginosa infection, ameliorated pulmonary inflammation and improved survival in P. aeruginosa pneumonia. CONCLUSIONS: These findings indicate that a prior infection with T. spiralis ameliorates experimental pulmonary inflammation and improves survival in P. aeruginosa pneumonia through a Th2-type response with eosinophils.