Recently， Asian Pacific Association for the Study of the Liver published the recommendations for the diagnosis and management of non-cirrhotic portal fibrosis （NCPF）/idiopathic portal hypertension （IPH）. The guidelines mainly elaborate on the definition， diagnosis， histological features， natural history， and management of NCPF/IPH， in order to strengthen the understanding of NCPF/IPH-related issues and establish a global consensus. This article makes an excerpt of the key statements in the guidelines.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Herb-induced liver injury(HILI)shows a high incidence rate and has great impacts on the clinical medication safety of traditional Chinese medicine and the healthy development of the industry.In recent years,the research on HILI has attracted wide attention and made remarkable progress,and related clinical diagnosis and treatment guidelines have been formulated and updated by the academic organizations in China and globally.This article compares the recent guidelines on HILI formulated by different organizations and elaborates on the main achievements in terms of mechanism of toxicity,clinical diagnosis and disease assessment,risk factors,and clinical prevention and treatment,and it also proposes the unmet needs,the research difficulties that need to be taken seriously,and possible prevention and treatment strategies.

Due to the diverse application forms of Chinese herbal medicine products,the wide range of users,and the complex conditions of medication in China,adverse events including herb-induced liver injury(HILI)occur frequently in recent years.In order to further understand HILI and standardize its risk management and prevention and treatment measures,this article discusses the risk management,clinical evaluation,prevention,and treatment of HILI based on related clinical research advances and experience in recent years.In the multiple links of traditional Chinese medicine including production and clinical application after marketing,the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events,involving product quality control,patient safety education,rational drug use by clinicians,regular monitoring,and graded and classified treatment,which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future.

Drug-induced liver injury （DILI） has a complex mechanism involving various pathways with a synergistic effect on each other and a causal relationship with each other， among which immune response plays an important role in the pathogenesis of DILI. In the context of genetic background， drug active metabolites， drug-molecule complexes， and danger signal molecules may be used as the trigger factors for immune response in DILI， activating the mechanism of drug antigenic hypersensitivity， P-i hypothesis， and danger signal mechanism in innate immunity. The cascade reaction of innate immunity and adaptive immunity leads to the imbalance of the innate immune tolerance of the liver and thus causes immunoinflammatory injury of liver tissue. This article mainly elaborates on the immunological mechanism of DILI， in order to provide new ideas for the research and development of therapeutic targets for DILI and the methods for avoiding adverse drug reactions.

Objective:To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease.Methods:53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes.Results:As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased ( P<0.05), while the spleen volume gradually increased ( P<0.05). The expression of CD31 and GS gradually increased ( P<0.05), and the expression of Ki67 first increased and then decreased ( P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume ( r=-0.609, P<0.001) and the total liver volume ( r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume ( r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume ( r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume ( r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV ( r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area( r=-0.511, P=0.009). Conclusion:As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

Objective:To investigate the protective effect of all-trans retinoic acid(ATRA)on the function of NK cells dam-aged by oxidative stress in liver fibrosis.Methods:Mouse model with liver injury was established by carbon tetrachloride(CCl4),biochemical and pathological assays were used to evaluate the degree of liver injury and fibrosis in mice,and changes of NK cells and oxidative stress injury in liver tissue of mice were observed.In vitro,NK92 cell lines damaged by H2O2 oxidative stress were evaluated the protective effect of ATRA.Results:Liver inflammation and fibrosis were suppressed and liver function was improved in CCl4 model mice by ATRA treatment.ATRA could increase SOD activity and GSH content in liver tissue,which promoted the proportion and num-ber of hepatic NK cells.ATRA could protect NK cells from oxidative damage and apoptosis induced by H2O2 in vitro.Conclusion:ATRA can ameliorate liver injury and fibrosis induced by CCl4,which may be related to the inhibition of oxidative stress on NK cells.