Liver fibrosis is a common pathological process associated with multiple chronic liver diseases. Recent advancements have significantly improved the non-invasive assessment of liver fibrosis. This article focuses on the exploration of hot topics, namely how noninvasive indicators can evaluate liver fibrosis reversal and predict clinical outcomes. Concurrently, it indicates that attention should be paid to the dynamic changes of noninvasive indicators, and population screening efforts should be strengthened to achieve early diagnosis and treatment of liver fibrosis so as to improve long-term clinical outcomes.

Objective:To explore the distribution characteristics of HBsAg levels in treatment-na?ve and treatment-experienced patients with chronic hepatitis B (CHB) in China.Methods:Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-na?ve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean± SD, and M( Q1, Q3). Results:A total of 13 505 treatment-na?ve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-na?ve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-na?ve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially.Conclusions:The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-na?ve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Liver fibrosis is a common pathological process associated with multiple chronic liver diseases. Recent advancements have significantly improved the non-invasive assessment of liver fibrosis. This article focuses on the exploration of hot topics, namely how noninvasive indicators can evaluate liver fibrosis reversal and predict clinical outcomes. Concurrently, it indicates that attention should be paid to the dynamic changes of noninvasive indicators, and population screening efforts should be strengthened to achieve early diagnosis and treatment of liver fibrosis so as to improve long-term clinical outcomes.

Objective:To explore the distribution characteristics of HBsAg levels in treatment-na?ve and treatment-experienced patients with chronic hepatitis B (CHB) in China.Methods:Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-na?ve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean± SD, and M( Q1, Q3). Results:A total of 13 505 treatment-na?ve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-na?ve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-na?ve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially.Conclusions:The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-na?ve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

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 order to achieve the global goal of eliminating viral hepatitis as a public health threat by 2030 proposed by the World Health Organization, it is of great importance to expand the treatment of chronic hepatitis B patients. Recent studies have shown that alanine aminotransferase (ALT) is associated with liver inflammation, fibrosis, hepatocellular carcinoma, and outcome events of liver disease. Besides, as a strategy for expanding antiviral therapy, reducing the treatment threshold of ALT can reduce the occurrence of liver cirrhosis, hepatocellular carcinoma, and liver-related death. In the Expert opinion on expanding antiviral therapy for chronic hepatitis B published in China in 2022, the treatment indication for chronic hepatitis B patients was updated to positive serum HBV DNA and ALT above the treatment threshold (30 U/L for male and 19 U/L for female), with the exclusion of other causes.

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.

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.