The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

Antiviral therapy (AVT) reduces the risk of hepatitis B virus-related hepatocellular carcinoma (HCC).

The difference in risk of HCC after hepatitis B surface antigen (HBsAg) seroclearance to the AVT status was explored.

Patients with chronic hepatitis B who achieved HBsAg seroclearance were retrospectively evaluated. The primary outcome was the development of HCC after HBsAg seroclearance.

Of the study population, 1280 (84.2%) and 241 (15.8%) patients achieved HBsAg seroclearance without (spontaneous clearance group) and with AVT (AVT-induced clearance group), respectively. HCC cumulative incidence was comparable between the two groups (hazard ratio [HR] = 0.461; log-rank test, p = 0.197), whereas it was significantly lower in the AVT-induced HBsAg clearance group than in the spontaneous HBsAg clearance group in inverse probability of treatment weighting analysis (HR = 0.442; log-rank test, p = 0.004). In multivariate analysis, spontaneous HBsAg clearance, albumin-bilirubin (ALBI) grade ≥ 2, cirrhosis, and platelet count < 50 × 109/L were independently associated with the increased risk of HCC. The newly established antiviral therapy, cirrhosis, ALBI, and platelet count (ACAP) scores had a C-index of 0.765, and the time-dependent areas under the curve of HCC prediction at 5 and 8 years were 0774 and 0.823, respectively.

The risk of HCC differed according to the AVT status after HBsAg seroclearance.

Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancers, with its incidence continually rising, posing a threat to socio-economic development. Currently, liver resection is the standard treatment for HCC. However, post-hepatectomy liver failure (PHLF) is a severe and formidable postoperative complication that increases patients' medical expenses and mortality risk. Additionally, liver failure can occur at any stage of HCC development, severely affecting patients' quality of life and prognosis.

Using the Web of Science Core Collection, this bibliometric study analyzed English articles and reviews on HCC and liver failure from 2003 to 2023. Bibliometric tools like CiteSpace, VOSviewer, and R-studio were employed for data visualization and analysis, focusing on publication trends, citation metrics, explosive intensity, and collaborative networks. Use the Comparative Toxicogenomics and Genecards databases to screen for genes related to liver failure, and perform enrichment analyses using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PubMed on the identified differentially expressed genes.

The study identified a significant increase in publications on HCC and liver failure, with key contributions from journals such as the World Journal of Gastroenterology and the Journal of Hepatology. The United States, China, and Japan were the leading countries in research output. Prominent authors and institutions, including Kudo Masatoshi and Sun Yat-sen University, were identified. Enrichment analysis showed drug metabolism, oxidative stress, lipid metabolism, and other pathways are closely related to this field. Research hotspots included risk prediction models and novel therapies.

This bibliometric analysis highlights the growing research interest and advancements in HCC and liver failure. Future research should focus on improving risk prediction, developing new therapies, and enhancing international collaboration to address these critical health issues.

Hepatitis B virus (HBV) remains a major global health problem. HBV DNA can be integrated into the human chromosomes. The integration in young cirrhotic chronic hepatitis B children has not been explored. This study aims to investigate HBV DNA integration in early childhood cirrhosis.

Biopsy liver specimens from cirrhotic and matched non-cirrhotic chronic hepatitis B children were collected. HBV DNA integration was detected through targeted HBV DNA fragment capture sequencing.

Twenty cirrhotic and 20 non-cirrhotic children with chronic hepatitis B were included in the study. The cirrhotic group included 14 males and 6 females, and the non-cirrhotic group included 13 males and 7 females. Compared to non-cirrhotic children, cirrhotic children had lower serum HBsAg quantification (p = 0.001). The median number of HBV integrants in the cirrhotic group was 59 and that in the non-cirrhotic group was 98. No significant difference existed between the two groups (p = 0.529). In the multivariate linear regression analysis, serum HBV DNA level was correlated with the number of HBV integrants (p < 0.001, R2 = 0.322). Six differential intragenic high-frequency viral integration sites in cirrhotic children were revealed, all of which have protein-coding functions.

Several frequently integrated genes were observed in early childhood cirrhosis. Detailed associations between genetic alterations induced by HBV integration and early childhood cirrhosis need further exploration.

The risk of hepatocellular carcinoma (HCC) and hepatic decompensation persists after hepatitis B surface antigen (HBsAg) seroclearance. This study aimed to develop and validate a machine learning model to predict the risk of liver-related outcomes (LROs) following HBsAg seroclearance.

A total of 4,787 consecutive patients who achieved HBsAg seroclearance between 2000 and 2022 were enrolled from six centers in South Korea and a territory-wide database in Hong Kong, comprising the training (n = 944), internal validation (n = 1,102), and external validation (n = 2,741) cohorts. Three machine learning-based models were developed and compared in each cohort. The primary outcome was the development of any LRO, including HCC, decompensation, and liver-related death.

During a median follow-up of 55.2 (IQR 30.1-92.3) months, 123 LROs were confirmed (1.1%/person-year) in the Korean cohort. The model with the best predictive performance in the training cohort was selected as the final model (designated as PLAN-B-CURE), which was constructed using a gradient boosting algorithm and seven variables (age, sex, diabetes, alcohol consumption, cirrhosis, albumin, and platelet count). Compared to previous HCC prediction models, PLAN-B-CURE showed significantly superior accuracy in the training cohort (c-index: 0.82 vs. 0.63-0.70, all p <0.001; area under the receiver-operating characteristic curve: 0.86 vs. 0.62-0.72, all p <0.01; area under the precision-recall curve: 0.53 vs. 0.13-0.29, all p <0.01). PLAN-B-CURE showed a reliable calibration function (Hosmer-Lemeshow test p >0.05) and these results were reproduced in the internal and external validation cohorts.

This novel machine learning model consisting of seven variables provides reliable risk prediction of LROs after HBsAg seroclearance that can be used for personalized surveillance.

Using large-scale multinational data, we developed a machine learning model to predict the risk of liver-related outcomes (i.e., hepatocellular carcinoma, decompensation, and liver-related death) after the functional cure of chronic hepatitis B (CHB). The new model named PLAN-B-CURE was constructed using seven variables (age, sex, alcohol consumption, diabetes, cirrhosis, serum albumin, and platelet count) and a gradient boosting machine algorithm, and it demonstrated significantly better predictive accuracy than previous models in both the training and validation cohorts. The inclusion of diabetes and significant alcohol intake as model inputs suggests the importance of metabolic risk factor management after the functional cure of CHB. Using seven readily available clinical factors, PLAN-B-CURE, the first machine learning-based model for risk prediction after the functional cure of CHB, may serve as a basis for individualized risk stratification.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly HCC and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease. Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients. The recent development of new therapeutic agents and modalities has opened unprecedented opportunities to refine primary, secondary, and tertiary HCC prevention strategies. For primary prevention (before exposure to risk factors), public health policies, such as universal HBV vaccination, have had a substantial prognostic impact. Secondary prevention (after or during active exposure to risk factors) includes regular HCC screening and chemoprevention. Emerging biomarkers and imaging modalities for HCC risk stratification and detection may enable individual risk-based personalized and cost-effective HCC screening. Clinical studies have suggested the potential utility of lipid-lowering, antidiabetic/obesity, and anti-inflammatory agents for secondary prevention, and some of them are being evaluated in prospective clinical trials. Computational and experimental studies have identified potential chemopreventive strategies directed at diverse molecular, cellular, and systemic targets for etiology-specific and/or agnostic interventions. Tertiary prevention (in conjunction with curative-intent therapies for HCC) is an area of active research with the development of new immune-based neoadjuvant/adjuvant therapies. Cholangiocarcinoma prevention may advance with recent efforts to elucidate risk factors. These advances will collectively lead to substantial improvements in liver cancer mortality rates.

The effects of age at HBsAg seroclearance on clinical outcomes and survival in chronic hepatitis B (CHB) have not been adequately assessed. We evaluated the impact of age at HBsAg seroclearance on long-term outcomes, along with how coexisting factors modified risks and life expectancy in CHB patients.

We used multi-state modeling approach to examine transitions through the CHB continuum in a longitudinal cohort study of male civil servants recruited in 1989-1992. Hepatic outcomes and deaths were identified by clinical evaluation and linkage with national health databases. Four sets of risk factors (CHB-related, metabolic, lifestyle, and genetic factors) were assessed.

Of 2551 HBsAg carriers, with follow-up until 2021 or death, 695 achieved HBsAg seroclearance, 490 developed cirrhosis (88 decompensated), 252 developed hepatocellular carcinoma (HCC), and 652 died. The cumulative rates for HCC were 1.1% and 1.5% at 10 years after HBsAg seroclearance, respectively, for patients achieving seroclearance at age 50 and 60; correspondingly, the rates for cirrhosis were 2.3% and 3.0%. Developing HBsAg seroclearance was associated with a reduced risk of cirrhosis (HR = 0.37, 95% CI 0.15-0.92) but not HCC. Patients experiencing HBsAg seroclearance lived longer years free of major liver diseases than HBsAg-persistent patients, and achieving seroclearance at age 50 (vs 60) led to a greater increase in the disease-free life expectancy. However, obesity and smoking were associated with adverse hepatic outcomes and loss of the disease-free life expectancy following HBsAg seroclearance.

Our findings highlight the benefit of earlier HBsAg seroclearance for gains in disease-free life expectancy and the impact of obesity and smoking on loss of the life years free of major liver diseases following HBsAg seroclearance.

Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up.

Excessive fat accumulation, biological clock dysregulation, viral infections, and sustained inflammatory responses can lead to liver inflammation, fibrosis, and cancer, thus promoting the development of chronic liver disease. A comprehensive understanding of the etiological factors leading to chronic liver disease and the intrinsic mechanisms influencing its onset and progression can aid in identifying potential targets for targeted therapy. Mitochondria, as key organelles that maintain the metabolic homeostasis of the liver, provide an important foundation for exploring therapeutic targets for chronic liver disease. Recent studies have shown that active ingredients in herbal medicines and their natural products can modulate chronic liver disease by influencing the structure and function of mitochondria. Therefore, studying how Chinese herbs target mitochondrial structure and function to treat chronic liver diseases is of great significance.

Investigating the prospects of herbal medicine the Lens of chronic liver disease based on mitochondrial structure and function.

A computerized search of PubMed was conducted using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "botanicals, mitochondria and chronic liver disease".Data from the Web of Science and Science Direct databases were also included. The research findings regarding herbal medicines targeting mitochondrial structure and function for the treatment of chronic liver disease are summarized.

A computerized search of PubMed using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "phytopharmaceuticals, mitochondria, and chronic liver disease", as well as the Web of Science and Science Direct databases was conducted to summarize information on studies of mitochondrial structure- and function-based Chinese herbal medicines for the treatment of chronic liver disease and to suggest that the effects of herbal medicines on mitochondrial division and fusion.The study suggested that there is much room for research on the influence of Chinese herbs on mitochondrial division and fusion.

Targeting mitochondrial structure and function is crucial for herbal medicine to combat chronic liver disease.

Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB).

To identify risk factors and construct a predictive model for HCC development.

We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong.

In the training cohort, HCC occurred in 102 patients during 24,019 person-years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time-dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low-, intermediate- and high-risk groups were 0.07%, 0.37% and 0.90%, respectively.

The CAMP-B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP-B score can be easily implemented in real-world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection.

This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed.

Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001).

The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB.

In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

The impact of the severity of sarcopenic obesity (SO) in nonalcoholic fatty liver disease (NAFLD) on the risk of significant liver fibrosis or cardiovascular disease (CVD) remains unclear. We aimed to identify high-risk subjects with SO for significant liver fibrosis or CVD among subjects with SO and NAFLD.

This multicenter, retrospective study involved 23,889 subjects with NAFLD who underwent a health screening program (2014-2020). Sarcopenia was defined based on gender-specific sarcopenia index cutoff using multi-frequency bioelectric impedance analysis. High-risk subjects with SO were defined as those with significant liver fibrosis by fibrosis-4 index >2.67 or atherosclerotic CVD risk score >20%. Multivariable logistic regression analysis for identifying high-risk subjects with SO was performed in a cross-sectional cohort with SO, and further validation was performed in a longitudinal cohort.

SO prevalence was 5.4% (n = 1297 of 23,889). Older age (unstandardized beta [β] = 3.23; P < .001), male (β = 1.66; P = .027), sarcopenia index (β = -6.25; P = .019), and metabolic syndrome (β = 1.75; P < .001) were significant risk factors for high-risk SO. Based on a high-risk SO screening model, high-risk subjects with SO had significantly higher odds of significant liver fibrosis (training: adjusted odds ratio [aOR], 3.72; validation: aOR, 2.38) or CVD (training: aOR, 5.20; validation: aOR, 3.71) than subjects without SO (all P < .001). In subgroup analyses, the cumulative incidence of significant liver fibrosis or CVD development was significantly higher in high-risk subjects with SO than in low-risk subjects with SO in a longitudinal cohort considering all-cause mortality and liver transplantation as competing risks (sub-distribution hazard ratio, 5.37; P < .001).

The high-risk screening model may enable the identification of high-risk subjects with SO with NAFLD.

We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification.

This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan-Meier curves were used to estimate RFS and OS for the different risk-score groups.

In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2-5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62-0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05).

Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections.

Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999-2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019.

During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02-1.46) higher risk of all-cause mortality in NHANES 1999-2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48-1.06) for heart disease, 1.44 (95% CI 1.01-2.05) for cancer, and 1.44 (95% CI 1.13-1.83) for other conditions, compared to those of participants who were anti-HBs positive.

Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive.

We examined the long-term incidence of hepatocellular carcinoma (HCC) and hepatic decompensation among chronic hepatitis B (CHB) patients who have achieved hepatitis B surface antigen (HBsAg) seroclearance.

All adult CHB-monoinfected patients who cleared HBsAg between January 2000 and December 2020 were identified using a territory-wide database in Hong Kong. Patients who underwent liver transplantation and/or developed HCC before HBsAg seroclearance or less than 6 months follow-up were excluded. The primary and secondary endpoints were HCC and hepatic decompensation respectively.

We identified 9,769 patients with CHB who achieved HBsAg seroclearance (mean age 57 years, 60.0% male, 13.2% cirrhosis); most had compensated liver function at HBsAg loss. At a median (25th-75th percentile) follow-up of 4.6 (2.2-8.4) years, 106 (1.1%) patients developed HCC. Patients who developed HCC were older, more likely to be male and have cirrhosis, and had higher alanine aminotransferase and lower platelets at the time of HBsAg loss than patients without HCC. The cumulative incidence of HCC remained steady 0-7 and 8-12 years after HBsAg loss (p = 0.898) (crude annual incidence drop: -0.04%, 95% CI -0.13% to 0.04%, p = 0.265). Moreover, 124/9,640 (1.3%) patients developed hepatic decompensation. The growth in cumulative incidence of hepatic decompensation decelerated 8-12 years after HBsAg loss (p = 0.009) (crude annual incidence drop: -0.23%, 95% CI -0.40% to -0.06%, p = 0.012). In multivariable analysis, HBsAg loss for over 7 years was associated with a reduced risk of hepatic decompensation (adjusted subdistribution hazard ratio [aSHR] 0.55, 95% CI 0.31-0.97, p = 0.039) but not HCC (aSHR 1.35, 95% CI 0.83-2.19, p = 0.230).

HCC risk persists in patients after HBsAg loss, whereas the risk of hepatic decompensation decreases over time.

Patients with chronic hepatitis B (CHB) still have a non-negligible risk of hepatocellular carcinoma (HCC) after 12 years of HBsAg seroclearance, especially among those with cirrhosis. The risk of developing hepatic decompensation decreases over time after HBsAg seroclearance. In clinical practice, although patients with CHB who cleared HBsAg have a more favourable clinical outcome than those who remain chronically infected, long-term HCC surveillance would still be necessary for patients with cirrhosis and other high-risk subgroups after HBsAg seroclearance.

In the era of antiviral therapy, the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus (HBV) replication to the pursuit of serological clearance of HBs surface antigen (HBsAg). Based on the life cycle of HBV, HBsAg originates from covalently closed circular DNA (cccDNA) and integrated HBV DNA, thus reflecting their transcriptional activity. Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA. HBsAg loss improves the recovery of abnormal immune function, which in turn, may further promote the clearance of residual viruses. Combined with functional cure and the great improvement of clinical outcomes, the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B (CHB). For many other risk factors besides HBV itself, patients with HBsAg loss still need regular monitoring. In this review, we summarized the evolution of CHB treatment, the origin of serum HBsAg, the pattern of HBsAg seroclearance, and the effect of HBsAg loss on immune function and disease outcomes. In addition, we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.

As a tribute to Dr Mike Bray, the following review of literature willbe mainly based on published data andconcepts, but will also contain my personal views, and in this respect could be more considered as a bioassay. Even though a cost-effective and excellent prophylactic vaccine exists since many years to protect against hepatitis B virus (HBV) infection, academic-researcher/drug-developers/stakeholders are still busy with the R&D of novel therapies that could eventually have an impact on its worldwide incidence. The Taiwanese experience have univocally demonstrated the effectiveness of constrained national HBV prophylactic vaccination programs to prevent the most dramatic HBV-induced end-stage liver disease, which is hepatocellular carcinoma; but yet the number of individuals chronically infected with the virus, for whom the existing prophylactic vaccine is no longer useful, remains high, with around 300 million individuals around the globe. In this review/bioassay, recent findings and novel concepts on prospective therapies against HBV infections will be discussed; yet it does not have the pretention to be exhaustive, as "pure immunotherapeutic concepts" will be mainly let aside (or referred to other reviews) due to a lack of expertise of this writer, but also due to the lack of, or incremental, positive results in clinical trials as-off today with these approaches.

Although hepatitis B virus surface antigen (HBsAg) serum clearance is an important milestone in the natural history of chronic hepatitis B virus (HBV) infection, HBsAg-negative patients are at risk of liver cancer and liver-related death, especially when progressive fibrosis is present. HBsAg-negative/anti-HBV core antibody-positive patients should be carefully evaluated and managed accordingly for the presence of significant liver fibrosis, other viral coinfections, occult HBV infection, risk of HBV reactivation, and hepatocellular carcinoma. Antiviral prophylaxis should be initiated in isolated anti-HBV core antibody patients receiving high-risk chemotherapy or biologics. Hepatocellular carcinoma surveillance with liver ultrasound and serum alpha-fetoprotein should be considered for patients with risk factors.

Hepatocellular carcinoma (HCC) or hepatoma is malignant cancer that starts from the main liver cells. Although various classical methods have been used for patients with HCC, various molecular mechanisms involved in HCC progression should be invested. Previous studies demonstrated that abnormal expression of long non-coding RNAs (lncRNAs) presented important roles in the pathogenesis of HCC cells. LncRNA TUG1 was found to mediate HCC cell growth, EMT, and metastasis. Therefore, targeting TUG1 and its downstream genes may be a suitable approach for patients with HCC. In this review, we summarized the potential roles of TUG1 in HCC.

Primary liver cancer is the seventh-most-common cancer worldwide and the fourth-leading cause of cancer mortality. In the current era of precision medicine, the diagnosis and management of liver cancer are full of challenges and prospects. Mesoporous nanoparticles are often designed as specific carriers of drugs and imaging agents because of their special morphology and physical and chemical properties. In recent years, the design of the elemental composition and morphology of mesoporous nanoparticles have greatly improved their drug-loading efficiency, biocompatibility and biodegradability. Especially in the field of primary liver cancer, mesoporous nanoparticles have been modified as highly tumor-specific imaging contrast agents and targeting therapeutic medicine. Various generations of complexes and structures have been determined for the complicated clinical management requirements. In this review, we summarize these advanced mesoporous designs in the different diagnostic and therapeutic fields of liver cancer and discuss the relevant advantages and disadvantages of transforming applications. By comparing the material properties, drug-delivery characteristics and application methods of different kinds of mesoporous materials in liver cancer, we try to help determine the most suitable drug carriers and information media for future clinical trials. We hope to improve the fabrication of biomedical mesoporous nanoparticles and provide direct evidence for specific cancer management.