Interferon-α suppresses hepatitis B virus enhancer II activity via the protein kinase C pathway

AbstractHBV has two enhancer (En) regions each of which promotes its own transcription. En II regulates production of pregenomic RNA, a key product of HBV replication, more strongly than En I. Although IFN-α has been found to suppress En I activity, its effect on En II activity has not been examined. Here we used luciferase assay to demonstrate that IFN-α suppresses En II activity. Analysis with several deletion/mutation constructs identified two major segments, nt 1703–1727 and nt 1746–1770, within the En II sequence as being responsible for the suppressive effects of IFN-α. Pre-treatment with protein kinase C (PKC) inhibitors blocked this effect regardless of the expression levels of phospho-STAT1 and Mx upon IFN-α stimulation. These results indicate that IFN-α suppresses En II activity via the PKC pathway, which may be an alternative suppressive pathway for HBV replication. (136 words)

Macrophages as a source of fibrosis biomarkers for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) are becoming major liver diseases worldwide. Liver fibrosis and cirrhosis are among the most significant risk factors of hepatocellular carcinoma (HCC) and associated with the long-term prognosis of NAFLD patients. To stratify the risk of HCC in NAFLD patients clinically, the discovery of non-invasive fibrosis markers is needed urgently. Liver macrophages play critical roles in the regulation of inflammation and fibrosis by interacting with hepatic stellate cells (HSCs) and other immune cells. Thus, it is rational to explore feasible biomarkers for liver fibrosis by focusing on macrophage-related factors. We examined serum factors comprehensively in multiple cohorts of NAFLD/NASH patients to determine whether they were correlated with the biopsy-proven fibrosis stage. We found that the serum levels of interleukin (IL)-34, YKL-40 and soluble Siglec-7 (sSiglec7) were closely associated with liver fibrosis and served as diagnostic biomarkers in patients with NAFLD/NASH. In the NAFLD liver, IL-34 was produced by activated fibroblasts, and YKL-40 and sSiglec-7 were secreted from macrophages. The sensitivity and specificity of these markers to detect advanced liver fibrosis varied, supporting the notion that the combination of these markers with other modalities is an option for clinical application

Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016

Abstract Background Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug–drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population. Methods This was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged ≥18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period. Results We analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period. Conclusions Patients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug–drug interactions

Additional file 2: of Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016

Table S2. Non-HCV-related medications prescribed at least once during the study period by age group. Description of data: The proportions of patients who received non-HCV-related medications at least once during the study period are summarised by age for both chronic HCV patients and non-HCV patients. (XLSX 184 kb

Setting hinge position distal to the proximal margin of the distal lateral femur reduces the maximum principal strains of the hinge area and risk of hinge fractures

Abstract Purpose The optimal hinge position to prevent hinge fractures in medial closing wedge distal femoral osteotomy (MCWDFO) based on the biomechanical background has not yet been well examined. This study aimed to examine the appropriate hinge position in MCWDFO using finite element (FE) analysis to prevent hinge fractures. Methods Computer‐aided design (CAD) models were created using composite replicate femurs. FE models of the MCWDFO with a 5° wedge were created with three different hinge positions: (A) 5 mm proximal to the proximal margin of the lateral epicondylar region, (B) proximal margin level and (C) 5 mm distal to the proximal margin level. The maximum and minimum principal strains in the cortical bone were calculated for each model. To validate the FE analysis, biomechanical tests were performed using composite replicate femurs with the same hinge position models as those in the FE analysis. Results In the FE analysis, the maximum principal strains were in the order of Models A > B > C. The highest value of maximum principal strain was observed in the area proximal to the hinge. In the biomechanical test, hinge fractures occurred in the area proximal to the hinge in Models A and B, whereas the gap closed completely without hinge fractures in Model C. Fractures occurred in an area similar to where the highest maximal principal strain was observed in the FE analysis. Conclusion Distal to the proximal margin of the lateral epicondylar region is an appropriate hinge position in MCWDFO to prevent hinge fractures. Level of Evidence Level V