A novel predictive model using routinely clinical parameters to predict liver fibrosis in patients with chronic hepatitis B A novel predictive model using routinely clinical parameters to predict liver fibrosis in patients with chronic hepatitis B

Mammalian orthoreoviruses (MRVs) are increasingly reported to cause various diseases in humans and other animals, with many possibly originating from bats, highlighting the urgent need to investigate the diversity of bat-borne MRVs (BtMRVs). Here, we report the detection and characterization of a reassortant MRV that was isolated from a bat colony in Xinjiang, China. The BtMRV showed a wide host and organ tropism and can efficiently propagate the cell lines of different animals. It caused mild damage in the lungs of the experimentally inoculated suckling mice and was able to replicate in multiple organs for up to three weeks post-inoculation. Complete genome analyses showed that the virus was closely related to MRVs in a wide range of animals. An intricate reassortment network was revealed between the BtMRV and MRVs of human, deer, cattle, civet and other bat species. Specifically, we found a bat-specific clade of segment M1 that provides a gene source for the reassortment of human MRVs. These data provide important insights to understand the diversity of MRVs and their natural circulation between bats, humans, and other animals. Further investigation and surveillance of MRV in bats and other animals are needed to control and prevent potential MRV-related diseases.

Liver diseases seriously challenge the health of chickens raised on scaled farms and cause tremendous economic losses to farm owners. The causative agents for liver diseases are still elusive, even though various pathogens, such as the hepatitis E virus, have been reported. In the winter of 2021, a liver disease was observed on a chicken farm in Dalian, China, which increased chicken mortality by up to 18%. We conducted panvirome profiling of the livers, spleens, kidneys, and recta of 20 diseased chickens. The viromic results revealed coinfection of multiple viruses, including pathogenic ones, in these organs. The viruses were highly identical to those detected in other provinces, and the vaccine and field strains of avian encephalomyelitis virus (AEV) and chicken infectious anemia virus (CIAV) cocirculated on the farm. In particular, the liver showed higher abundance of AEV and multiple fowl adenoviruses than other organs. Furthermore, the liver also contracted avian leukemia virus and CIAV. Experimental animals with infected liver samples developed minor to medium lesions of the liver and showed a virus abundance profile for AEV across internal organs similar to that in the original samples. These results suggest that coinfection with multiple pathogenic viruses influences the occurrence and development of infectious liver disease. The results also highlight that strong farm management standards with strict biosafety measures are needed to minimize the risk of pathogenic virus introduction to the farm.

To observe longitudinally the expression of Programmed death 1(PD-1) on peripheral blood T cells in chronic hepatitis B patients underwent antiviral treatment with entecavir (ETV) and to explore the relationship between PD-1 expression and HBeAg seroconversion. Twenty HBeAg positive patients underwent antiviral treatment with ETV were followed up for 51 weeks. 14 patients remained HBeAg positive and 6 patients achieved HBeAg seroconversion. Peripheral blood was collected at six time points: T0: baseline, T1: 2-4week; T2: 5-10week; T3: 11-20week; T4: 21-30week: T5: 31-51week. PD-1 expressions on T cells were assessed by flow cytometry. Serum HBV DNA loads were determined by real-time fluorescent quantitative polymerase chain reaction (PCR) and serum ALT levels were examined at the same time. At baseline, serum HBV DNA load of patients without HBeAg seroconversion and with HBeAg seroconversion were (7.54+/-0.67) log10 copies/ml and (7.30+/-0.79) log10 copies/ml (P more than 0.05), the ALT levels were (187.26+/-184.15) U/L and (272.17+/-215.07) U/L (P more than 0.05), PD-1 exprissions on CD4+ T cells were 6.04%+/-3.71% and 6.77%+/-2.88% (P more than 0.05), PD-1 exprissions on CD8+ T cells were 6.39%+/-3.33% and 8.88%+/-2.84% (P more than 0.05). After ETV treatment, serum HBV DNA loads and ALT levels both decreased gradually, which was positively correlated with PD-1 expressions on CD4+ and CD8+ T cells (r=0.212, P = 0.05; r=0.377, P less than 0.01; r=0.279, P less than 0.05; r=0.347, P less than 0.01). During the same monitoring period, the HBV DNA loads, ALT levels and PD-1 expressions on T cells of the patients with HBeAg seroconversion decreased significantly as compared with the patients without HBeAg seroconversion. Besides, the decrease of HBV DNA loads during period deltaT0-T1 and deltaT0-T2 and PD-1 expressions on CD8+ T cells during period deltaT0-T2 and deltaT0-T3 were significantly different between these two kinds of patients (49.9% vs 37.3%, P less than 0.05; 56.7% vs 47.4%, P less than 0.05; 70.1% vs -4.2%, P less than 0.05; 66.9% vs 24.5%, P less than 0.05). The rapid decrease of PD-1 expression on peripheral CD8+ T cells after antiviral treatment with ETV is positvely correlated with the decrease of serum HBV DNA loads and may be used as a predictive index for HBeAg seroconversion in HBeAg positive patients.