The global chronic hepatitis B (CHB) guidelines have gradually expanded treatment indications in order to accelerate the elimination and improve the treatment rate of hepatitis B virus (HBV) infection. This article analyzes the new treatment concepts for chronic hepatitis B at home and abroad from two aspects: expanding treatment by paying more attention to the long-term prognosis of the disease and maximizing the use of existing drugs in order to achieve the early goal of the World Health Organization's of eliminating viral hepatitis by 2030.

Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

In March 2024,the World Health Organization released the latest version of guidelines for the prevention,diagnosis,care and treatment for people with chronic hepatitis B infection.The guidelines were updated in several aspects,including expanding and simplifying the indications for chronic hepatitis B treatment,adding alternative antiviral treatment regimens,broadening the indications for antiviral therapy to prevent mother-to-child transmission,improving the diagnosis of hepatitis B virus,and adding hepatitis D virus(HDV)testing.This article summarizes and gives an excerpt of the recommendations in the guidelines.

In order to reduce the disease burden of chronic hepatitis B (CHB) and improve the treatment rate of CHB, the indications for anti-viral therapy have been gradually expanded and simplified in guidelines for the prevention and treatment of CHB released by Chinese Medical Association from 2005 to 2022. This article elaborates on the evolution in the indications for anti-viral therapy in CHB from the five aspects of converging indications of HBeAg-positive and HBeAg-negative CHB, reduction in the treatment threshold of HBV DNA, reduction in the treatment threshold of serum alanine aminotransferase, emphasis on the risk factors for disease progression, and gradual loosening of the requirements for virological indicators in patients with liver cirrhosis.

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Objective:To investigate the difference in the radiation sensitivity of hematopoietic stem and progenitor cells (HSPCs) derived from fetal liver and bone marrow.Methods:HSPCs from fetal liver of 14.5 d embryo or bone marrow of 8 week-old mice were isolated to receive a single dose of 5 or 10 Gy irradiation in vitro using a 60Co irradiator. Twelve hours later, the cell apoptosis, mitochondrial reactive oxygen species (ROS) level, colony formation ability and DNA damage in HSPCs were detected. Freshly isolated HSPCs were injected into lethally irradiated CD45.1 + C57BL/6J mice (4.5 Gy+ 5 Gy with an interval of 30 min) Chimerism rate, lineage constitution, and cell cycle were analyzed 12 weeks after transplantation. Results:Compared with bone marrow HSPCs after irradiation, the percentage of apoptosis in fetal liver HSPCs was significantly higher ( t=16.21, 12.27, P<0.05), the level of ROS was dramatically elevated ( t=68.72, 18.89, P<0.05). At 10 Gy, fetal liver HSPCs could not form colonies at all ( t=12.41, 15.67, 9.46, P<0.05). γ-H2AX immunofluorescence staining showed that the DNA damage of fetal liver HSPCs was more severe after irradiation, and the number of Foci formed was significantly higher than that of bone marrow HSPCs ( t=2.27, 2.03, P< 0.05), which indicated that fetal liver HSPCs were more sensitive to radiation. The chimerism rate of transplanted fetal liver HSPCs was lower than that of bone marrow cells ( t=5.84, P<0.05) with a higher proportion of myeloid lineage, suggesting that fetal liver HSPCs had lower in vivo reconstitution capacity than bone marrow HSPCs and were more prone to myeloid differentiation. The cell cycle of bone marrow HSPCs from transplanted chimeric mice was examined, and the proportion of S-phase was significantly higher in the fetal liver group than that in the bone marrow group ( t=2.89, P<0.05). Mitochondrial stress results showed that fetal liver HSPCs had higher basal respiratory capacity ( t=39.19, P<0.05), proton leakage ( t=6.64, P<0.05), ATP production ( t=9.33, P<0.05), and coupling efficiency ( t=7.10, P<0.05) than bone marrow c-Kit + cells, while respiratory reserve capacity ( t=5.53, P< 0.05) was lower than that of bone marrow c-Kit + cells. Conclusions:HSPCs derived from fetal liver display higher radiosensitivty compared with bone marrow HSPCs, laying the foundation for an in-depth illustration of the effects of radiation on hematopoietic stem cells at different developmental stages.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective:To study the effect of different doses of 60Co γ-ray ionizing radiation on mitochondrial function in mouse hematopoietic stem and progenitor cells (HSPCs). Methods:C57BL/6 mice were divided into control group, 1 Gy irradiation group and 4.5 Gy irradiation group. The mitochondrial functions were detected at 12 h and 24 h after irradiation, including ROS level, membrane potential, mitochondrial structure, and mitochondrial stress. Bone marrow c-Kit + cells received a single 15 Gy irradiation in vitro, after 24 h, mitochondrial function was detected. Results:It was found that mice leukocytes ( t=12.41, 18.31, 16.48, 14.16, 19.08, 20.25, P<0.05), red blood cells ( t=4.81, 6.62, P<0.05) and platelets ( t=4.33, 6.68, P<0.05) were significantly reduced. The numbers of bone marrow colony formation unit ( t=16.27, 55.66, 17.06, 43.75, P<0.05), and HSPCs ( t=5.16, 11.55, P<0.05) were decreased dose-dependently post-irradiation. Under 1 Gy irradiation, the mitochondrial function and mitochondrial basal metabolic index of HSPCs ( t= 7.36, 3.68, 4.58, 3.15, 3.15, P<0.05) were enhanced at 24 h post-irradiation. Under 4.5 Gy irradiation, mitochondrial number, mitochondrial membrane potential ( t=12.29, 10.46, P<0.05), maximal respiration and spare respiratory capacity were decreased ( t=7.81, 5.78, 6.70, 5.83, P<0.05), ROS level was increased ( t=4.63, 4.12, P<0.05). The basal respiration and oxidative phosphorylated ATP production were reduced at 12 h after irradiation ( t=8.48, 3.80, P<0.05); and the proton leakage was increased ( t=6.57, P<0.05) and coupling efficiency was reduced ( t=11.43, P<0.05) at 24 h after irradiation. In cultured c-Kit + cells, the level of ROS ( t=11.30, P<0.05) and the maximum respiration and spare respiratory capacity were increased ( t=4.25, 3.44, P<0.05) while the mitochondrial membrane potential was decreased ( t=34.92, P<0.05) significantly. Conclusions:A method for systematically assessing mitochondrial function in HSPCs was established, and the effect of ionizing radiation on mitochondrial function of HSPCs was clarified, laying a foundation for further revealing the mechanism of ionizing radiation-induced mitochondrial damage in HSPCs.

Hepatic fibrosis is a response to various types of hepatic injury, which can lead to cirrhosis and its complications. In recent years, in patients with viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, autoimmune liver disease and others the fibrosis or even early cirrhosis can be regressed if the etiology are controlled. Liver biopsy is still the gold standard for assessing fibrosis reversal, but non-invasive methods such as transient elastography hold great promise due to the ease to use for dynamic monitoring. Mechanisms of hepatic fibrosis reversal include extracellular matrix degradation, hepatocyte regeneration, and vascular remodeling. Presently, novel agents targeting the steps of fibrosis are urgently need for achieving regression of liver fibrosis.